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1.
Pancreatology ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39327123

RESUMO

BACKGROUND: Although universal germline genetic testing is recommended for patients with exocrine pancreatic cancer (PC), access to genetic testing remains limited in low- and middle-income countries. This study aims to narrow the gap in our understanding of the spectrum of germline pathogenic and likely pathogenic variants (PVs) in cancer susceptibility genes in the Mexican population. METHODS: The landscape of PVs in cancer susceptibility genes was identified by next-generation sequencing multigene panel assays among patients with PC who were enrolled in the Clinical Cancer Genomics Community Research Network prospective registry in Mexico City. RESULTS: From August 2019 to April 2023, 137 patients underwent genetic testing. The median age at diagnosis was 60 years (range 36-85), 58.4 % were women, and 38.7 % were metastatic at diagnosis. The frequency of germline PVs was 16 % (n = 22): ATM 36.4 % (n = 8), CDKN2A/p16INK4A 27.3 % (n = 6), BRCA2 9.1 % (n = 2), PALB2 9.1 % (n = 2), CHEK2 9.1 % (n = 2), TP53 4.5 % (n = 1), and NF1 4.5 % (n = 1). Additionally, 2 carriers of monoallelic germline variants in MUTYH were identified. No significant differences were observed between carriers and non-carriers in terms of family history of pancreatic cancer. CONCLUSIONS: We identified a significant frequency of actionable germline PVs in Mexicans with PC, wherein the majority were in a broad spectrum of genes associated with the homologous recombination DNA repair mechanism. Most pancreatic cancer associated PVs were detected in non-BRCA genes, so our findings support the recommendation of multigene panel testing for genetic cancer risk assessment of Mexican individuals with PC.

2.
J Natl Compr Canc Netw ; 22(3): 158-166, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38626807

RESUMO

BACKGROUND: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium. METHODS: PRECEDE is a multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18-90 years) are enrolled into 1 of 7 cohorts based on family history and pathogenic germline variant (PGV) status. From April 1, 2020, to November 21, 2022, a total of 3,402 participants were enrolled in 1 of 7 study cohorts, with 1,759 (51.7%) meeting criteria for the highest-risk cohort (Cohort 1). Cohort 1 HRIs underwent germline testing and pancreas imaging by MRI/MR-cholangiopancreatography or endoscopic ultrasound. RESULTS: A total of 1,400 participants in Cohort 1 (79.6%) had completed baseline imaging and were subclassified into 3 groups based on familial PC (FPC; n=670), a PGV and FPC (PGV+/FPC+; n=115), and a PGV with a pedigree that does not meet FPC criteria (PGV+/FPC-; n=615). One HRI was diagnosed with stage IIB PC on study entry, and 35.1% of HRIs harbored pancreatic cysts. Increasing age (odds ratio, 1.05; P<.001) and FPC group assignment (odds ratio, 1.57; P<.001; relative to PGV+/FPC-) were independent predictors of harboring a pancreatic cyst. CONCLUSIONS: PRECEDE provides infrastructure support to increase access to clinical surveillance for HRIs worldwide, while aiming to drive early PC detection advancements through longitudinal standardized clinical data, imaging, and biospecimen captures. Increased cyst prevalence in HRIs with FPC suggests that FPC may infer distinct biological processes. To enable the development of PC surveillance approaches better tailored to risk category, we recommend adoption of subclassification of HRIs into FPC, PGV+/FPC+, and PGV+/FPC- risk groups by surveillance protocols.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/epidemiologia , Detecção Precoce de Câncer/métodos , Estudos Prospectivos , Predisposição Genética para Doença , Imageamento por Ressonância Magnética
3.
Cancer ; 125(1): 18-44, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30281145

RESUMO

Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.


Assuntos
Melanoma/prevenção & controle , Protetores contra Radiação/uso terapêutico , Neoplasias Cutâneas/prevenção & controle , Animais , Anticarcinógenos/uso terapêutico , Quimioprevenção , Ensaios Clínicos Fase III como Assunto , Desenvolvimento de Medicamentos , Reposicionamento de Medicamentos , Feminino , Humanos , Masculino , Neoplasias Cutâneas/tratamento farmacológico
4.
Front Oncol ; 13: 1141810, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37293588

RESUMO

Background: International chemoprevention preferences and approaches in Lynch syndrome (LS) and APC-associated polyposis, including Familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) have not been previously explored. Aim: To describe current chemoprevention strategies for patients with LS or FAP/AFAP (referred to collectively as FAP) practiced by members of four international hereditary cancer societies through administration of a survey. Results: Ninety-six participants across four hereditary gastrointestinal cancer societies responded to the survey. Most respondents (91%, 87/96) completed information regarding their demographics and practice characteristics relating to hereditary gastrointestinal cancer and chemoprevention clinical practices. Sixty-nine percent (60/87) of respondents offer chemoprevention for FAP and/or LS as a part of their practice. Of the 75% (72/96) of survey respondents who were eligible to answer practice-based clinical vignettes based off of their responses to ten barrier questions regarding chemoprevention, 88% (63/72) of those participants completed at least one case vignette question to further characterize chemoprevention practices in FAP and/or LS. In FAP, 51% (32/63) would offer chemoprevention for rectal polyposis, with sulindac - 300 mg (18%, 10/56) and aspirin (16%, 9/56) being the most frequently selected options. In LS, 93% (55/59) of professionals discuss chemoprevention and 59% (35/59) frequently recommend chemoprevention. Close to half of the respondents (47%, 26/55) would recommend beginning aspirin at time of commencement of the patient's first screening colonoscopy (usually at age 25yrs). Ninety-four percent (47/50) of respondents would consider a patient's diagnosis of LS as an influential factor for aspirin use. There was no consensus on the dose of aspirin (≤100 mg, >100 mg - 325 mg or 600 mg) to offer patients with LS and there was no agreement on how other factors, such as BMI, hypertension, family history of colorectal cancer, and family history of heart disease, would affect the recommendation for aspirin use. Possible harm among older patients (>70 years) was identified as the most common reason to discourage aspirin use. Conclusion: Although chemoprevention is widely discussed and offered to patients with FAP and LS by an international group of hereditary gastrointestinal cancer experts, there is significant heterogeneity in how it is applied in clinical practice.

5.
Clin Cancer Res ; 27(10): 2678-2697, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33414132

RESUMO

Five years ago, the Melanoma Research Foundation (MRF) conducted an assessment of the challenges and opportunities facing the melanoma research community and patients with melanoma. Since then, remarkable progress has been made on both the basic and clinical research fronts. However, the incidence, recurrence, and death rates for melanoma remain unacceptably high and significant challenges remain. Hence, the MRF Scientific Advisory Council and Breakthrough Consortium, a group that includes clinicians and scientists, reconvened to facilitate intensive discussions on thematic areas essential to melanoma researchers and patients alike, prevention, detection, diagnosis, metastatic dormancy and progression, response and resistance to targeted and immune-based therapy, and the clinical consequences of COVID-19 for patients with melanoma and providers. These extensive discussions helped to crystalize our understanding of the challenges and opportunities facing the broader melanoma community today. In this report, we discuss the progress made since the last MRF assessment, comment on what remains to be overcome, and offer recommendations for the best path forward.


Assuntos
COVID-19/prevenção & controle , Oncologia/métodos , Melanoma/terapia , Guias de Prática Clínica como Assunto , SARS-CoV-2/isolamento & purificação , Neoplasias Cutâneas/terapia , Pesquisa Biomédica/métodos , Pesquisa Biomédica/tendências , COVID-19/epidemiologia , COVID-19/virologia , Humanos , Oncologia/organização & administração , Oncologia/tendências , Melanoma/diagnóstico , SARS-CoV-2/fisiologia , Neoplasias Cutâneas/diagnóstico
6.
JAMA Dermatol ; 156(9): 1004-1011, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32725204

RESUMO

Importance: Use of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care. Objective: To develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies. Evidence Review: The MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed. Findings: The MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility. Conclusions and Relevance: More evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.


Assuntos
Tomada de Decisão Clínica/métodos , Perfilação da Expressão Gênica/normas , Melanoma/diagnóstico , Guias de Prática Clínica como Assunto , Neoplasias Cutâneas/diagnóstico , Consenso , Conferências de Consenso como Assunto , Humanos , Melanoma/genética , Melanoma/patologia , Melanoma/terapia , Estadiamento de Neoplasias , Prognóstico , Biópsia de Linfonodo Sentinela/normas , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia
7.
Am J Gastroenterol ; 104(9): 2222-32, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19491824

RESUMO

OBJECTIVES: Colorectal cancer (CRC) is a feared complication of chronic ulcerative colitis (UC). Annual endoscopic surveillance is recommended for the detection of early neoplasia. 5-Aminosalicylates (5-ASAs) may prevent some UC-associated CRC. Therefore, in patients prescribed 5-ASAs for maintenance of remission, annual surveillance might be overly burdensome and inefficient. We aimed to determine the ideal frequency of surveillance in patients with UC maintained on 5-ASAs. METHODS: We performed systematic reviews of the literature, and created a Markov computer model simulating a cohort of 35-year-old men with chronic UC, followed until the age of 90 years. Twenty-two strategies were modeled: natural history (no 5-ASA or surveillance), surveillance without 5-ASA at intervals of 1-10 years, 5-ASA plus surveillance every 1-10 years, and 5-ASA alone. The primary outcome was the ideal interval of surveillance in the setting of 5-ASA maintenance, assuming a third-party payer was willing to pay $100,000 for each quality-adjusted life-year (QALY) gained. RESULTS: In the natural history strategy, the CRC incidence was 30%. Without 5-ASA, annual surveillance was the ideal strategy, preventing 89% of CRC and costing $69,100 per QALY gained compared with surveillance every 2 years. 5-ASA alone prevented 49% of CRC. In the setting of 5-ASA, surveillance every 3 years was ideal, preventing 87% of CRC. 5-ASA with surveillance every 2 years cost an additional $147,500 per QALY gained, and 5-ASA with annual surveillance cost nearly $1 million additional per QALY gained compared with every 2 years. In Monte Carlo simulations, surveillance every 2 years or less often was ideal in 95% of simulations. CONCLUSIONS: If 5-ASA is efficacious chemoprevention for UC-associated CRC, endoscopic surveillance might be safely performed every 2 years or less often. Such practice could decrease burdens to patients and on endoscopic resources with a minimal decrease in quality-adjusted length of life, because 5-ASA with annual surveillance may cost nearly $1 million per additional QALY gained.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colonoscopia/economia , Neoplasias Colorretais/diagnóstico , Mesalamina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Colite Ulcerativa/complicações , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Simulação por Computador , Análise Custo-Benefício , Humanos , Masculino , Cadeias de Markov , Programas de Rastreamento/economia , Pessoa de Meia-Idade
9.
J Adv Pract Oncol ; 10(5): 428-439, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33457057

RESUMO

The association of BRCA mutation status with hypersensitivity reactions (HSRs) to carboplatin has gained interest in recent years, particularly in patients with ovarian, fallopian tube, and primary peritoneal cancer. The primary objective of this study is to determine whether the presence of BRCA mutations increased the likelihood of HSRs to carboplatin. The incidence of HSRs to paclitaxel and symptom grade based on the Common Terminology Criteria for Adverse Events, version 4.0, were explored as secondary endpoints. A retrospective chart review of patients with ovarian, fallopian tube, or primary peritoneal cancer at the University of Arizona Cancer Center who underwent treatment with carboplatin-containing regimens and received genetic testing was performed. Institutional review board approval was obtained for this study. Fisher's exact test was used to analyze the primary outcome. Out of 167 initial patients, 62 with germline test results constituted the evaluable sample. 15 of 62 (24.2%) BRCA-tested patients were treated with carboplatin monotherapy, while 44 of 62 (71.0%) patients were treated with paclitaxel-containing regimens. Hypersensitivity reactions occurred in 4 of 13 (30.8%) BRCA-mutated patients and 22 of 49 (44.9%) BRCA wild-type patients (p = .5291). Hypersensitivity reactions to paclitaxel occurred in 1 of 13 (7.7%) BRCA-mutated patients and 26 of 49 (53.1%) BRCA wild-type patients (p = .0039). Overall, there were 11 grade 1 reactions, 14 grade 2 reactions, and 16 grade 3 reactions to carboplatin. All reactions to carboplatin in BRCA-mutated patients were grade 1. All paclitaxel reactions manifested as grade 2. The sample size was the main study limitation. The presence of BRCA mutations was not statistically significantly associated with a higher incidence of HSRs to carboplatin, but was statistically significant with regards to paclitaxel.

10.
Clin Genitourin Cancer ; 15(1): 31-41.e4, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27916626

RESUMO

BACKGROUND: This analysis describes the outcome for patients who received targeted therapy (TT) prior to or following high-dose interleukin-2 (HD IL-2). PATIENTS AND METHODS: Patients with renal cell carcinoma (n = 352) receiving HD IL-2 were enrolled in ProleukinR Observational Study to Evaluate the Treatment Patterns and Clinical Response in Malignancy (PROCLAIMSM) beginning in 2011. Statistical analyses were performed using datasets as of September 24, 2015. RESULTS: Overall, there were 4% complete response (CR), 13% partial response (PR), 39% stable disease (SD), and 43% progressive disease (PD) with HD IL-2. The median overall survival (mOS) was not reached in patients with CR, PR, or SD, and was 15.5 months in patients with PD (median follow-up, 21 months). Sixty-one patients had prior TT before HD IL-2 with an overall response rate (ORR) to HD IL-2 of 19% (1 CR, 9 PR) and an mOS of 22.1 months. One hundred forty-nine patients received TT only after HD IL-2 with an mOS of 35.5 months. One hundred forty-two patients had no TT before or after HD IL-2, and mOS was not reached. The mOS was 8.5 months in PD patients who received HD IL-2 without follow-on TT and 29.7 months in PD patients who received follow-on TT after HD IL-2. CONCLUSIONS: HD IL-2 as sole front-line therapy, in the absence of added TT, shows extended clinical benefit (CR, PR, and SD). Patients with PD after HD IL-2 appear to benefit from follow-on TT. Patients who progressed on TT and received follow-on HD IL-2 experienced major clinical benefit. HD IL-2 therapy should be considered in eligible patients.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Interleucina-2/análogos & derivados , Neoplasias Renais/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/imunologia , Intervalo Livre de Doença , Feminino , Humanos , Imunoterapia , Interleucina-2/administração & dosagem , Interleucina-2/uso terapêutico , Neoplasias Renais/imunologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento
11.
Melanoma Manag ; 4(1): 13-37, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28758010

RESUMO

Melanoma is usually apparent on the skin and readily detected by trained medical providers using a routine total body skin examination, yet this malignancy is responsible for the majority of skin cancer-related deaths. Currently, there is no national consensus on skin cancer screening in the USA, but dermatologists and primary care providers are routinely confronted with making the decision about when to recommend total body skin examinations and at what interval. The objectives of this paper are: to propose rational, risk-based, data-driven guidelines commensurate with the US Preventive Services Task Force screening guidelines for other disorders; to compare our proposed guidelines to recommendations made by other national and international organizations; and to review the US Preventive Services Task Force's 2016 Draft Recommendation Statement on skin cancer screening.

12.
Oncology (Williston Park) ; 20(3): 269-76; discussion 285-6, 288-9, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16629258

RESUMO

Approximately 6% of colorectal cancers can be attributed to recognizable heritable germline mutations. Familial adenomatous polyposis is an autosomal dominant syndrome classically presenting with hundreds to thousands of adenomatous colorectal polyps that are caused by mutations in the APC gene. Adenomas typically develop in the midteens in these patients, and colorectal cancer is a virtual certainty if this condition is untreated. A low-penetrance susceptibility allele that is common in Jews from Eastern Europe, APC 11307K, confers a two-fold increased risk of colorectal cancer without the full expression of familial adenomatous polyposis. Biallelic mutations in the MYH gene are associated with an attenuated familial adenomatous polyposis phenotype. Lynch syndrome (hereditary nonpolyposis colorectal cancer) is an autosomal dominant disorder characterized by early onset of colorectal cancer with microsatellite instability. Mutations in mismatch repair genes lead to a lifetime colon cancer risk of 85% in these patients; carcinomas of the endometrium, ovary, and other organs also occur with increased frequency. Although adenomas are not characteristic of the hamartomatous polyp syndromes such as juvenile polyposis and Peutz-Jeghers syndrome, individuals with these diseases have a markedly increased risk of colorectal cancer relative to the general population. In this review, we will describe the phenotypes, genotypes, diagnosis, and management of hereditary colon cancer syndromes.


Assuntos
Neoplasias Colorretais/genética , Testes Genéticos , Alelos , Neoplasias Colorretais/diagnóstico , Suscetibilidade a Doenças , Humanos , Mutação , Medição de Risco , Fatores de Risco
14.
J Clin Oncol ; 34(2): 186-93, 2016 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-26527778

RESUMO

PURPOSE: To assist in determining barriers to an oncology career incorporating cancer prevention, the American Society of Clinical Oncology (ASCO) Cancer Prevention Workforce Pipeline Work Group sponsored surveys of training program directors and oncology fellows. METHODS: Separate surveys with parallel questions were administered to training program directors at their fall 2013 retreat and to oncology fellows as part of their February 2014 in-training examination survey. Forty-seven (67%) of 70 training directors and 1,306 (80%) of 1,634 oncology fellows taking the in-training examination survey answered questions. RESULTS: Training directors estimated that ≤ 10% of fellows starting an academic career or entering private practice would have a career focus in cancer prevention. Only 15% of fellows indicated they would likely be interested in cancer prevention as a career focus, although only 12% thought prevention was unimportant relative to treatment. Top fellow-listed barriers to an academic career were difficulty in obtaining funding and lower compensation. Additional barriers to an academic career with a prevention focus included unclear career model, lack of clinical mentors, lack of clinical training opportunities, and concerns about reimbursement. CONCLUSION: Reluctance to incorporate cancer prevention into an oncology career seems to stem from lack of mentors and exposure during training, unclear career path, and uncertainty regarding reimbursement. Suggested approaches to begin to remedy this problem include: 1) more ASCO-led and other prevention educational resources for fellows, training directors, and practicing oncologists; 2) an increase in funded training and clinical research opportunities, including reintroduction of the R25T award; 3) an increase in the prevention content of accrediting examinations for clinical oncologists; and 4) interaction with policymakers to broaden the scope and depth of reimbursement for prevention counseling and intervention services.


Assuntos
Escolha da Profissão , Bolsas de Estudo , Oncologia/educação , Neoplasias/prevenção & controle , Humanos , Sociedades Médicas , Inquéritos e Questionários , Estados Unidos
15.
Cancer Prev Res (Phila) ; 9(2): 128-34, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26712942

RESUMO

Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventive efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin. Individuals with visible cutaneous sun damage were eligible. Subjects were randomized to one of the three groups: topical DFMO applied twice daily, topical diclofenac applied daily, or DFMO plus diclofenac. The treatment was limited to an area on the left forearm, and the duration of use was 90 days. We hypothesized that combination therapy would have increased efficacy compared with single-agent therapy. The primary outcome was change in karyometric average nuclear abnormality (ANA) in the treated skin. Individuals assessing the biomarkers were blinded regarding the treatment for each subject. A total of 156 subjects were randomized; 144 had baseline and end-of-study biopsies, and 136 subjects completed the study. The ANA unexpectedly increased for all groups, with higher values correlating with clinical cutaneous inflammation. Nearly all of the adverse events were local cutaneous effects. One subject had cutaneous toxicity that required treatment discontinuation. Significantly more adverse events were seen in the groups taking diclofenac. Overall, the study indicated that the addition of topical DFMO to topical diclofenac did not enhance its activity. Both agents caused inflammation on a cellular and clinical level, which may have confounded the measurement of chemopreventive effects. More significant effects may be observed in subjects with greater baseline cutaneous damage.


Assuntos
Diclofenaco/administração & dosagem , Eflornitina/administração & dosagem , Antebraço/patologia , Ceratose Actínica/prevenção & controle , Neoplasias Cutâneas/prevenção & controle , Pele/efeitos dos fármacos , Administração Tópica , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Anticarcinógenos/administração & dosagem , Feminino , Seguimentos , Antebraço/efeitos da radiação , Humanos , Ceratose Actínica/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Pele/metabolismo , Pele/patologia , Neoplasias Cutâneas/metabolismo , Luz Solar/efeitos adversos
16.
Cancer Prev Res (Phila) ; 8(5): 342-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25586903

RESUMO

Bilateral salpingo-oophorectomy (BSO) has become the standard-of-care for risk reduction in women at hereditary risk of ovarian cancer. Although this procedure significantly decreases both the incidence of and mortality from ovarian cancer, it affects quality of life, and the premature cessation of ovarian function may have long-term health hazards. Recent advances in our understanding of the molecular pathways of ovarian cancer point to the fallopian tube epithelium as the origin of most high-grade serous cancers (HGSC). This evolving appreciation of the role of the fallopian tube in HGSC has led to the consideration of salpingectomy alone as an option for risk management, especially in premenopausal women. In addition, it is postulated that bilateral salpingectomy with ovarian retention (BSOR), may have a public health benefit for women undergoing benign gynecologic surgery. In this review, we provide the rationale for salpingectomy as an ovarian cancer risk reduction strategy.


Assuntos
Neoplasias Epiteliais e Glandulares/prevenção & controle , Neoplasias Ovarianas/prevenção & controle , Procedimentos Cirúrgicos Profiláticos , Salpingectomia/estatística & dados numéricos , Carcinoma Epitelial do Ovário , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Feminino , Humanos , Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Ovarianas/epidemiologia , Procedimentos Cirúrgicos Profiláticos/estatística & dados numéricos , Fatores de Risco , Comportamento de Redução do Risco
17.
Clin Pharmacol ; 5(Suppl 1): 21-7, 2013 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-24113540

RESUMO

Ipilimumab is a monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 that has been approved by the US Food and Drug Administration for the treatment of metastatic melanoma. Phase III trials have demonstrated an overall survival benefit with its use when compared with standard treatments and other investigational therapies. However, the drug poses a notable challenge, given its propensity for toxicity, and requires close surveillance when administered in clinical practice. This review discusses the mechanism of action for ipilimumab, its preclinical data, and the clinical trials that led to its approval by the Food and Drug Administration in 2011.

18.
Fam Cancer ; 12(1): 83-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23179792

RESUMO

The Database of Individuals at High Risk for Breast, Ovarian, or Other Hereditary Cancers at the Arizona Cancer Center in Tucson, Arizona assesses cancer risk factors and outcomes in patients with a family history of cancer or a known genetic mutation. We analyzed the subset of clinic probands who carry deleterious BRCA gene mutations to identify factors that could explain why mutations in BRCA2 outnumber those in BRCA1. Medical, family, social, ethnic and genetic mutation histories were collected from consenting patients' electronic medical records. Differences between BRCA1 and BRCA2 probands from this database were analyzed for statistical significance and compared to published analyses. A significantly higher proportion of our clinic probands carry mutations in BRCA2 than BRCA1, compared with previous reports of mutation prevalence. This also holds true for the Hispanic sub-group. Probands with BRCA2 mutations were significantly more likely than their BRCA1 counterparts to present to the high risk clinic without a diagnosis of cancer. Other differences between the groups were not significant. Six previously unreported BRCA2 mutations appear in our clinic population. The increased proportion of probands carrying deleterious BRCA2 mutations is likely multifactorial, but may reflect aspects of Southern Arizona's unique ethnic heritage.


Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Adulto , Arizona/epidemiologia , Feminino , Testes Genéticos , Humanos , Pessoa de Meia-Idade , Mutação , Prevalência , Fatores de Risco
19.
Cancer Prev Res (Phila) ; 5(12): 1341-4, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23221207

RESUMO

In this issue (beginning on page 1368), Kreul and colleagues report a retrospective review of long-term efficacy and toxicity for subjects participating in a phase III study of difluoromethylornithine (DFMO) for prevention of nonmelanoma skin cancer (NMSC). They conclude that those treated with DFMO had a nonsignificant, persistent decrease in NMSC after completion of treatment and that treatment with DFMO did not result in late toxicity after the discontinuation of treatment. We review the data on DFMO as a chemopreventive agent for skin and other cancers, discuss the necessary qualities of a cancer chemopreventive agent, and reflect on the requirements for a well-conducted cancer chemoprevention study, including the rationale for long-term follow-up in cancer prevention studies.


Assuntos
Eflornitina/farmacologia , Neoplasias Cutâneas/prevenção & controle , Feminino , Humanos , Masculino
20.
Clin Med Insights Oncol ; 6: 275-86, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22904648

RESUMO

Immune augmentation with ipilimumab, an anti-CTLA-4 monoclonal antibody, has joined the ranks of approved immunologic agents for the treatment of metastatic melanoma. Phase III studies of ipilimumab in metastatic melanoma have demonstrated an overall survival advantage as compared to other approved and investigational therapies. However, the adverse effects associated with this medication are unique and often require management with steroids or other immunosuppressants. In addition, the time to response differs with ipilimumab as compared to traditional chemotherapy, and alternative means of assessment of response have been proposed. In this review, we will summarize the basic science of this treatment, its preclinical evaluation, and the clinical trials leading to its approval. We will also discuss the details regarding its use, assessment of response to this drug and other immune-related therapies, and further directions for investigation.

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