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1.
CA Cancer J Clin ; 71(5): 437-454, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34255347

RESUMO

Radiation therapy (RT) is a curative treatment for many malignancies and provides effective palliation in patients with tumor-related symptoms. However, the biophysical effects of RT are not specific to tumor cells and may produce toxicity due to exposure of surrounding organs and tissues. In this article, the authors review the clinical context, pathophysiology, risk factors, presentation, and management of RT side effects in each human organ system. Ionizing radiation works by producing DNA damage leading to tumor death, but effects on normal tissue may result in acute and/or late toxicity. The manifestation of toxicity depends on both cellular characteristics and affected organs' anatomy and physiology. There is usually a direct relationship between the radiation dose and volume to normal tissues and the risk of toxicity, which has led to guidelines and recommended dose limits for most tissues. Side effects are multifactorial, with contributions from baseline patient characteristics and other oncologic treatments. Technological advances in recent decades have decreased RT toxicity by dramatically improving the ability to deliver RT that maximizes tumor dose and minimizes organ dose. Thus the study of RT-associated toxicity is a complex, core component of radiation oncology training that continues to evolve alongside advances in cancer management. Because RT is used in up to one-half of all patients with cancer, an understanding of its acute and late effects in different organ systems is clinically pertinent to both oncologists and nononcologists.


Assuntos
Neoplasias/radioterapia , Lesões por Radiação , Relação Dose-Resposta à Radiação , Humanos , Cuidados Paliativos , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Lesões por Radiação/fisiopatologia , Lesões por Radiação/terapia , Fatores de Risco
2.
Oncologist ; 25(5): e798-e807, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31852811

RESUMO

BACKGROUND: The addition of bevacizumab to chemotherapy improved outcomes for patients with metastatic colon cancer. E5204 was designed to test whether the addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and definitive surgery, could improve overall survival (OS) in patients with stage II/III adenocarcinoma of the rectum. SUBJECTS, MATERIALS, AND METHODS: Patients with stage II/III rectal cancer who had completed neoadjuvant 5-fluorouracil-based chemoradiation and had undergone complete resection were enrolled. Patients were randomized to mFOLFOX6 (Arm A) or mFOLFOX6 with bevacizumab (Arm B) administered every 2 weeks for 12 cycles. RESULTS: E5204 registered only 355 patients (17% of planned accrual goal) as it was terminated prematurely owing to poor accrual. At a median follow-up of 72 months, there was no difference in 5-year overall survival (88.3% vs. 83.7%) or 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. The rate of treatment-related grade ≥ 3 adverse events (AEs) was 68.8% on Arm A and 70.7% on Arm B. Arm B had a higher proportion of patients who discontinued therapy early as a result of AEs and patient withdrawal than did Arm A (32.4% vs. 21.5%, p = .029).The most common grade 3-4 treatment-related AEs were neutropenia, leukopenia, neuropathy, diarrhea (without prior colostomy), and fatigue. CONCLUSION: At 17% of its planned accrual, E5204 did not meet its primary endpoint. The addition of bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS in patients with stage II/III rectal cancer. IMPLICATIONS FOR PRACTICE: At 17% of its planned accrual, E5204 was terminated early owing to poor accrual. At a median follow-up of 72 months, there was no significant difference in 5-year overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. Despite significant advances in the treatment of rectal cancer, especially in improving local control rates, the risk of distant metastases and the need to further improve quality of life remain a challenge. Strategies combining novel agents with chemoradiation to improve both distant and local control are needed.


Assuntos
Fluoruracila , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/uso terapêutico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/uso terapêutico , Qualidade de Vida , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia
3.
J Surg Res ; 254: 118-124, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32428729

RESUMO

BACKGROUND: The impact of time to surgical resection after neoadjuvant external beam radiation therapy (EBRT) in the high-grade soft tissue and retroperitoneal sarcomas has not been well established. We aimed to evaluate how surgical timing from EBRT affects oncologic and perioperative outcomes. METHODS: We performed a single institution retrospective cohort study of patients with biopsy-proven, high-grade sarcoma who completed neoadjuvant EBRT and resection from January 1, 1999 to September 1, 2018. We collected demographic and clinicopathologic variables, stratifying patients by time interval between EBRT and surgery: <6, 6-8, 8-10, and >10 wk. Primary outcomes collected were as follows: disease-free survival, overall survival, and perioperative complications. RESULTS: Of the 269 patients identified, 146 met inclusion criteria. The median follow-up was 24 mo. Overall and local recurrence were 37% (n = 54) and 14.4% (n = 21), respectively. Time to surgery did not affect recurrence (P = 0.82) or survival (P = 0.88). Positive margins (odds ratio 2.7, confidence interval 1.14, 6.51, P < 0.05) were predictive of recurrence. Primary tumor location, surgical timing, histology, and intraoperative radiation therapy were not associated with differences in recurrence. The overall complication rate was 28%, with 63% from wound infections. Fewer postoperative complications occurred in the < 6-wk cohort versus > 6-wk cohort (15% versus 38%, P < 0.05). CONCLUSIONS: We found no difference in oncologic outcomes associated with the timing of surgical resection after EBRT. Patients undergoing resection >6 wk were at higher risk for all complications without impacting wound complication rates. Future studies may include preoperative optimization of patients requiring delays in surgical planning to decrease perioperative complication rates.


Assuntos
Terapia Neoadjuvante/métodos , Sarcoma/radioterapia , Sarcoma/cirurgia , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retroperitoneais/radioterapia , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
4.
Nanomedicine ; 18: 189-195, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30858085

RESUMO

CRLX101 is a nanoparticle-drug conjugate with a camptothecin payload. We assessed the toxicity and pathologic complete response (pCR) rate of CRLX101 with standard neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. A single-arm study was conducted with a 3 + 3 dose escalation phase Ib followed by phase II at the maximum tolerated dose (MTD). Thirty-two patients were enrolled with 29 (91%) patients having T3/4 and 26 (81%) N1/2 disease. In phase Ib, no patient experienced a dose limiting toxicity (DLT) with every other week dosing, while 1/9 patients experienced a DLT with weekly dosing. The weekly MTD was identified as 15 mg/m2. The most common grade 3-4 toxicity was lymphopenia, with only 1 grade 4 event. pCR was achieved in 6/32 (19%) patients overall and 2/6 (33%) patients at the weekly MTD. CRLX101 at 15 mg/m2 weekly with neoadjuvant CRT is a feasible combination strategy with an excellent toxicity profile. Clinicaltrials.gov registration NCT02010567.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/uso terapêutico , Capecitabina/uso terapêutico , Ciclodextrinas/uso terapêutico , Nanopartículas/química , Terapia Neoadjuvante , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Capecitabina/efeitos adversos , Estudos de Coortes , Ciclodextrinas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/patologia
5.
Cancer ; 124(11): 2347-2354, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29579339

RESUMO

BACKGROUND: The purpose of the current study was to determine quality of life and tumor control from a prospective phase 2 clinical trial evaluating deintensified chemoradiotherapy for favorable risk, human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma. METHODS: Patients with T0-T3, N0-N2c, M0, p16-positive disease and a minimal smoking history were treated with 60 grays of intensity-modulated radiotherapy with concurrent weekly intravenous cisplatin (30 mg/m2 ). The primary study endpoint was the pathologic complete response rate based on biopsy of the primary site and dissection of pretreatment positive lymph node regions. The pathologic complete response rate as previously reported was 86%. Herein, the authors report secondary endpoint measures of local control, regional control, cause-specific survival, distant metastasis-free survival, and overall survival, and patient-reported outcomes (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [EORTC QLQ-C30] and the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events [PRO-CTCAE]). RESULTS: A total of 44 patients enrolled with a median follow-up of 36 months (88% with ≥2 years). The 3-year local control, regional control, cause-specific survival, distant metastasis-free survival, and overall survival rates were 100%, 100%, 100%, 100%, and 95%, respectively. The mean before and 3-year after EORTC QOL scores were: global: 80 of 78; swallowing: 11 of 11; dry mouth: 16 of 41; and sticky saliva: 6 of 29. The mean before and 3-year after PRO-CTCAE scores were: swallowing: 0.4 of 0.7; and dry mouth: 0.4 of 1.4. Approximately 39% of patients required a feeding tube (median duration, 15 weeks; none were permanent). There were no ≥grade 3 late adverse events reported. CONCLUSIONS: For patients with favorable-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma, a substantially decreased intensity of therapy with 60 grays of intensity-modulated radiotherapy and weekly low-dose cisplatin produced better preservation of quality of life compared with standard therapies while maintaining excellent 3-year tumor control and survival. Cancer 2018;124:2347-54. © 2018 American Cancer Society.


Assuntos
Quimiorradioterapia/métodos , Neoplasias Orofaríngeas/terapia , Infecções por Papillomavirus/terapia , Qualidade de Vida , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Idoso , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Intervalo Livre de Progressão , Estudos Prospectivos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Fatores de Tempo
6.
Nature ; 463(7283): 899-905, 2010 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-20164920

RESUMO

A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappaBeta pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.


Assuntos
Variações do Número de Cópias de DNA/genética , Dosagem de Genes/genética , Neoplasias/genética , Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Amplificação de Genes/genética , Genômica , Humanos , Família Multigênica/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides , Neoplasias/classificação , Neoplasias/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Transdução de Sinais , Proteína bcl-X/genética
7.
J Hepatocell Carcinoma ; 11: 443-454, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476559

RESUMO

Background: We aim to better characterize stereotactic body radiation therapy (SBRT)-related hepatic biochemical toxicity in patients with multiple intrahepatic lesions from hepatocellular carcinoma (HCC). Methods: We conducted a retrospective analysis of patients with HCC who underwent SBRT for 2 or more synchronous or metachronous liver lesions. We collected patient characteristics and dosimetric data (mean liver dose [MLD], cumulative effective volume [Veff], cumulative volume of liver receiving 15 Gy [V15Gy], and cumulative planning target volume [PTV]) along with liver-related toxicity (measured by albumin-bilirubin [ALBI] and Child-Pugh [CP] scores). A linear mixed-effects model was used to assess the effect of multi-target SBRT on changes in ALBI. Results: There were 25 patients and 56 lesions with median follow-up of 29 months. Eleven patients had synchronous lesions, and 14 had recurrent lesions treated with separate SBRT courses. Among those receiving multiple SBRT courses, there were 7 lesions with overlap of V15Gy (median V15Gy overlap: 35 mL, range: 0.5-388 mL). There was no association between cumulative MLD, Veff, V15Gy, or PTV and change in ALBI. Four of 25 patients experienced non-classic radiation-induced liver disease (RILD), due to an increase of CP score by ≥2 points 3 to 6 months after SBRT. Sixteen of 25 patients experienced an increase in ALBI grade by 1 or more points 3 to 6 months after SBRT. Comparing the groups that received SBRT in a single course versus multiple courses revealed no statistically significant differences in liver toxicity. Conclusion: Liver SBRT for multiple lesions in a single or in separate courses is feasible and with acceptable risk of hepatotoxicity. Prospective studies with a larger cohort are needed to better characterize safety in this population.

8.
Pract Radiat Oncol ; 14(1): 28-46, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37921736

RESUMO

Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.


Assuntos
Neoplasias Esofágicas , Radioterapia (Especialidade) , Cirurgiões , Humanos , Estados Unidos , Terapia Combinada , Neoplasias Esofágicas/radioterapia , Junção Esofagogástrica
9.
Ann Thorac Surg ; 117(1): 15-32, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37921794

RESUMO

Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.


Assuntos
Neoplasias Esofágicas , Radioterapia (Especialidade) , Cirurgiões , Humanos , Estados Unidos , Terapia Combinada , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/cirurgia
10.
Pract Radiat Oncol ; 14(2): 134-145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38244026

RESUMO

PURPOSE: External beam radiation therapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, the Barcelona Clinic Liver Cancer system does not recommend the use of EBRT in HCC due to a lack of sufficient evidence and intends to perform an individual patient level meta-analysis of ablative EBRT in this population. However, there are many types of EBRT described in the literature with no formal definition of what constitutes "ablative." Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC. METHODS AND MATERIALS: Fundamental parameters related to dose, fractionation, radiobiology, target identification, and delivery technique were identified by a steering committee to generate 7 Key Criteria (KC) that would define ablative EBRT for HCC. Using a modified Delphi (mDelphi) method, experts in the use of EBRT in the treatment of HCC were surveyed. Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of ≥70% was used to define consensus for answers to each KC. RESULTS: Of 40 invitations extended, 35 (88%) returned responses. In the first round, 3 of 7 KC reached consensus. In the second round, 100% returned responses and consensus was reached in 3 of the remaining 4 KC. The distribution of answers for one KC, which queried the a/b ratio of HCC, was such that consensus was not achieved. Based on this analysis, ablative EBRT for HCC was defined as a BED10 ≥80 Gy with daily imaging and multiphasic contrast used for target delineation. Treatment breaks (eg, for adaptive EBRT) are allowed, but the total treatment time should be ≤6 weeks. Equivalent dose when treating with protons should use a conversion factor of 1.1, but there is no single conversion factor for carbon ions. CONCLUSIONS: Using a mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empirical data are required to define the a/b of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/radioterapia , Consenso , Neoplasias Hepáticas/radioterapia , Instituições de Assistência Ambulatorial , Carbono
11.
Cancer ; 119(16): 3092-9, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23674290

RESUMO

BACKGROUND: Randomized controlled trials (RCTs) are commonly used to inform clinical practice; however, it is unclear how generalizable RCT data are to patients in routine clinical practice. The authors of this report assessed the availability and applicability of randomized evidence guiding medical decisions in a cohort of patients who were evaluated for consideration of definitive management in a radiation oncology clinic. METHODS: The medical records of consecutive, new patient consultations between January and March 2007 were reviewed. Patient medical decisions were classified as those with (Group 1) or without (Group 2) available, relevant level I evidence (phase 3 RCT) supporting recommended treatments. Group 1 medical decisions were further divided into 3 groups based on the extent of fulfilling eligibility criteria for each RCT: Group 1A included decisions that fulfilled all eligibility criteria; Group 1B, decisions that did not fulfill at least 1 minor eligibility criteria; or Group 1C, decisions that did not fulfill at least 1 major eligibility criteria. Patient and clinical characteristics were tested for correlations with the availability of evidence. RESULTS: Of the 393 evaluable patients, malignancies of the breast (30%), head and neck (18%), and genitourinary system (14%) were the most common presenting primary disease sites. Forty-seven percent of all medical decisions (n = 451) were made without available (36%) or applicable (11%) randomized evidence to inform clinical decision making. Primary tumor diagnosis was significantly associated with the availability of evidence (P < .0001). CONCLUSIONS: A significant proportion of medical decisions in an academic radiation oncology clinic were made without available or applicable level I evidence, underscoring the limitations of relying solely on RCTs for the development of evidence-based health care.


Assuntos
Neoplasias/radioterapia , Radioterapia (Especialidade)/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/radioterapia , Medicina Baseada em Evidências , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Garantia da Qualidade dos Cuidados de Saúde , Neoplasias Urogenitais/radioterapia , Adulto Jovem
12.
J Surg Res ; 185(1): 245-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23769633

RESUMO

BACKGROUND: Local recurrence (LR) rates in patients with retroperitoneal sarcoma (RPS) are high, ranging from 40% to 80%, with no definitive studies describing the best way to administer radiation. Intraoperative electron beam radiation therapy (IOERT) provides a theoretical advantage for access to the tumor bed with reduced toxicity to surrounding structures. The goal of this study was to evaluate the role of IOERT in high-risk patients. METHODS: An institutional review board approved, single institution sarcoma database was queried to identify patients who received IOERT for treatment of RPS from 2/2001 to 1/2009. Data were analyzed using the Kaplan-Meier method, Cox regression, and Fisher Exact tests. RESULTS: Eighteen patients (median age 51 y, 25-76 y) underwent tumor resection with IOERT (median dose 1250 cGy) for primary (n = 13) and recurrent (n = 5) RPS. Seventeen patients received neoadjuvant radiotherapy. Eight high-grade and 10 low-grade tumors were identified. Median tumor size was 15 cm. Four patients died and two in the perioperative period. Median follow-up of survivors was 3.6 y. Five patients (31%) developed an LR in the irradiated field. Three patients with primary disease (25%) and two (50%) with recurrent disease developed an LR (P = 0.5). Four patients with high-grade tumors (57%) and one with a low-grade tumor (11%) developed an LR (P = 0.1). The 2- and 5-y OS rates were 100% and 72%. Two- and 5-y LR rates were 13% and 36%. CONCLUSIONS: Using a multidisciplinary approach, we have achieved low LR rates in our high-risk patient population indicating that IOERT may play an important role in managing these patients.


Assuntos
Radioterapia/métodos , Neoplasias Retroperitoneais/radioterapia , Neoplasias Retroperitoneais/cirurgia , Sarcoma/radioterapia , Sarcoma/cirurgia , Adulto , Idoso , Terapia Combinada , Bases de Dados Factuais/estatística & dados numéricos , Elétrons/uso terapêutico , Feminino , Seguimentos , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/prevenção & controle , Dosagem Radioterapêutica , Neoplasias Retroperitoneais/mortalidade , Fatores de Risco , Sarcoma/mortalidade , Taxa de Sobrevida
13.
Hepatol Commun ; 7(7)2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37314737

RESUMO

BACKGROUND AIMS: Early-stage HCC can be treated with thermal ablation or stereotactic body radiation therapy (SBRT). We retrospectively compared local progression, mortality, and toxicity among patients with HCC treated with ablation or SBRT in a multicenter, US cohort. APPROACH RESULTS: We included adult patients with treatment-naïve HCC lesions without vascular invasion treated with thermal ablation or SBRT per individual physician or institutional preference from January 2012 to December 2018. Outcomes included local progression after a 3-month landmark period assessed at the lesion level and overall survival at the patient level. Inverse probability of treatment weighting was used to account for imbalances in treatment groups. The Cox proportional hazard modeling was used to compare progression and overall survival, and logistic regression was used for toxicity. There were 642 patients with 786 lesions (median size: 2.1 cm) treated with ablation or SBRT. In adjusted analyses, SBRT was associated with a reduced risk of local progression compared to ablation (aHR 0.30, 95% CI: 0.15-0.60). However, SBRT-treated patients had an increased risk of liver dysfunction at 3 months (absolute difference 5.5%, aOR 2.31, 95% CI: 1.13-4.73) and death (aHR 2.04, 95% CI: 1.44-2.88, p < 0.0001). CONCLUSIONS: In this multicenter study of patients with HCC, SBRT was associated with a lower risk of local progression compared to thermal ablation but higher all-cause mortality. Survival differences may be attributable to residual confounding, patient selection, or downstream treatments. These retrospective real-world data help guide treatment decisions while demonstrating the need for a prospective clinical trial.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirurgia , Adulto , Humanos , Carcinoma Hepatocelular/radioterapia , Estudos Retrospectivos , Radiocirurgia/efeitos adversos , Neoplasias Hepáticas/radioterapia , Seleção de Pacientes
14.
Cancer ; 117(12): 2620-8, 2011 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-21656739

RESUMO

BACKGROUND: The purpose of this study was to assess the efficacy and safety of 5-fluorouracil (5FU) and gemcitabine administered concurrently with radiation in patients with locally advanced, nonmetastatic pancreatic cancer. METHODS: Eligible patients had histologically confirmed pancreatic adenocarcinoma deemed locally unresectable without evidence of metastatic disease. In addition, all patients underwent laparoscopy or laparotomy before study entry to rule out peritoneal carcinomatosis. Patients received radiation therapy (50.4 Gy) with concurrent infusional 5FU (200 mg/m(2) 5 days/week) and weekly gemcitabine (200 mg/m(2) ). After a 3-week break, patients received weekly gemcitabine at 1000 mg/m(2) for 3 of 4 weeks, for 4 cycles. The primary endpoint of the trial was the proportion of patients surviving 9 months from study entry. Secondary endpoints included objective tumor response, CA19-9 response, overall survival (OS) time to progression (TTP), and toxicity. RESULTS: Between November 2001 and October 2004, 81 patients were enrolled, 78 of whom were eligible for analysis. With a median follow-up of 55.2 months, the median OS was 12.2 months (95% confidence interval [CI], 10.9-14.9) and the median TTP was 10 months (95% CI, 6.4-12.0). An objective tumor response was seen in 19 patients (25%), and among 56 patients with an elevated CA19-9 at baseline, 29 (52%) had a sustained CA19-9 response. Overall, 41% of patients had grade 3 or greater treatment-related gastrointestinal adverse events. CONCLUSIONS: The combination of 5FU, gemcitabine, and radiation is well tolerated. Survival is comparable with the best results of other recent studies of 5FU and radiation or gemcitabine and radiation.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Fluoruracila/uso terapêutico , Neoplasias Pancreáticas/terapia , Adenocarcinoma/mortalidade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno CA-19-9/sangue , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Gencitabina
15.
Artigo em Inglês | MEDLINE | ID: mdl-34651094

RESUMO

Despite the well-understood benefits of biomarker and genetic testing in precision medicine, uptake remains low, particularly for patients with low socioeconomic status and minority ethnic backgrounds. Patients report having limited familiarity with testing terminology and may not be able to accurately explain testing's role in treatment decisions. Patient confusion and lack of understanding is exacerbated by a multiplicity of overlapping terms used in communicating about testing. A LUNGevity Foundation-led working group composed of five professional societies, 23 patient advocacy groups, and 19 industry members assessed and recommended specific terms for communicating with patients on testing for tumor characteristics and germline mutations. METHODS: Members completed a precision oncology testing framework analysis (biomarkers, germline variants, testing modalities, biospecimen, and commonly used testing terms) for nine solid tumors and blood cancers. The evaluation was segmented into terms that distinguish between somatic and germline testing. Additional data were captured in a comprehensive survey (1,650 respondents) led by FORCE (Facing Our Risk of Cancer Empowered) on patient preferences on germline testing terms. RESULTS: Thirty-three terms were noted in patient education related to biomarker, genetic, and genomic testing. Biomarker testing was selected as the preferred term for testing for somatic (acquired) alterations and other biomarkers. Genetic testing for an inherited mutation and genetic testing for inherited cancer risk were selected as the preferred terms for testing for germline variants. CONCLUSION: Democratizing comprehension about precision oncology testing through intentional use of plain language and common umbrella terminology by oncology health care providers and others in the oncology ecosystem may help improve understanding and communication, and facilitate shared decision making about the role of appropriate testing in treatment decisions and other aspects of oncology care.


Assuntos
Neoplasias , Medicina de Precisão , Consenso , Ecossistema , Testes Genéticos , Humanos , Neoplasias/diagnóstico
16.
Clin Cancer Res ; 27(20): 5472-5481, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34312215

RESUMO

To address the need for clinical investigators in oncology, American Association for Cancer Research (AACR) and American Society for Clinical Oncology (ASCO) established the Methods in Clinical Cancer Research Workshop (MCCRW). The workshop's objectives were to: (i) provide training in the methods, design, and conduct of clinical trials; (ii) ensure that clinical trials met federal and international ethical guidelines; (iii) evaluate the effectiveness of the workshop; and (iv) create networking opportunities for young investigators with mentoring senior faculty. Educational methods included: (i) didactic lectures, (ii) Small Group Discussion Sessions, (iii) Protocol Development Groups, and (iv) one-on-one mentoring. Learning focused on the development of an Institutional Review Board (IRB)-ready protocol, which was submitted on the last day of the workshop. Evaluation methods included: (i) pre- and postworkshop tests, (ii) students' workshop evaluations, (iii) faculty's ratings of protocol development, (iv) students' productivity in clinical research after the workshop, and (v) an independent assessment of the workshop. From 1996 to 2014, 1,932 students from diverse backgrounds attended the workshop. There was a significant improvement in the students' level of knowledge from the pre- to the postworkshop exams (P < 0.001). Across the classes, student evaluations were very favorable. At the end of the workshop, faculty rated 92% to 100% of the students' protocols as ready for IRB submission. Intermediate and long-term follow-ups indicated that more than 92% of students were actively involved in patient-related research, and 66% had implemented five or more protocols. This NCI-sponsored MCCRW has had a major impact on the training of clinicians in their ability to design and implement clinical trials in cancer research.


Assuntos
Pesquisa Biomédica/economia , Pesquisa Biomédica/educação , Organização do Financiamento , Oncologia , Neoplasias , Pesquisadores/economia , Pesquisadores/educação , Sociedades Médicas , Pesquisa Biomédica/métodos , Humanos , Estados Unidos
17.
Oncology ; 78(3-4): 181-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20414006

RESUMO

PURPOSE: NF-kappaB is an antiapoptotic transcription factor that has been shown to be a mediator of treatment resistance. Bcl-3 is a regulator of NF-kappaB that may play a role in oncogenesis. The goal of this study was to correlate the activation status of NF-kappaB and Bcl-3 with clinical outcome in a group of patients with metastatic colorectal cancer (CRC). METHODS: A retrospective study of 23 patients who underwent surgical resection of CRC at the University of North Carolina (UNC). Activation of NF-kappaB was defined by nuclear expression of select components of NF-kappaB (p50, p52, p65) and Bcl-3. Tissue microarrays were created from cores of normal mucosa, primary tumor, lymph node metastases and liver metastases in triplicate from disparate areas of the blocks, and an intensity score was generated by multiplying intensity (0-3+) by percent of positive tumor cells. Generalized estimating equations were used to note differences in intensity scores among normal mucosa and nonnormal tissues. Cox regression models were fit to see if scores were significantly associated with overall survival. RESULTS: p65 NE was significantly higher in primary tumor and liver metastases than normal mucosa (both p < 0.01). p50 nuclear expression was significantly higher for all tumor sites than for normal mucosa (primary tumor and lymph node metastases p < 0.0001, liver metastases p < 0.01). Bcl-3 nuclear expression did not differ significantly between normal mucosa and tumor; however, nuclear expression in primary tumor for each of these components was strongly associated with survival: the increase in hazard for each 50-point increase in nuclear expression was 91% for Bcl-3, 66% for p65, and 52% for p50 (all p < 0.05). CONCLUSIONS: Activation of canonical NF-kappaB subunits p50 and p65 as measured by nuclear expression is strongly associated with survival suggesting NF-kappaB as a prognostic factor in this disease. Primary tumor nuclear expression appears to be as good as, or better than, metastatic sites at predicting prognosis. Bcl-3 nuclear expression is also negatively associated with survival and deserves further study in CRC.


Assuntos
Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Transcrição/metabolismo , Idoso , Proteína 3 do Linfoma de Células B , Núcleo Celular/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Metástase Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Prognóstico , Modelos de Riscos Proporcionais
18.
Adv Radiat Oncol ; 5(4): 656-658, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32775777

RESUMO

Medicine in the United States has generally followed ethical principles espoused by Immanuel Kant where the individual patient takes priority in decision-making. With the advent of coronavirus disease 2019 as a major health event, radiation oncologists in some situations need to alter the manner in which they act with individual patients. The well-being of health care workers and society as a whole needs to be considered in management decisions. During the time of a pandemic, ethics principles may be based more on a utilitarian approach that emphasizes the common good. Thus, at times treatment decisions might result in delays in initiating therapy, modifying the radiation treatment course (such as to a short course rather than a long course of therapy), and the sequence of therapies, all to minimize viral exposure. It is important that altered therapy is based as much as possible on institutional or departmental decisions and, to the extent possible, not on a case-by-case basis. However, in all situations, we need to still respect the individual's autonomy and fully inform patients of our decisions and the reasons for those decisions.

19.
Int J Radiat Oncol Biol Phys ; 118(5): 1164-1166, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38492967
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