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Purpose: Over 87,000 adolescents and young adults (AYAs) are diagnosed with cancer in the United States each year. Improvement in outcomes in the AYA population has lagged that of both younger and older patients. This decrement may be attributable to several factors, including insufficient supportive care services. Our team modified the Needs Assessment & Service Bridge (NA-SB) tool, utilizing an iterative approach with patient and clinician stakeholders to meet the needs of the AYA population at a large Midwestern Cancer Center. Methods: We recruited a 10-member AYA Advisory Board (AB) from our Cancer Center patients, and met five times over 9 months to discuss supportive care and the NA-SB. We recruited a multidisciplinary group of oncology clinicians to assess content validity and conducted interviews with nine clinician stakeholders to discuss implementation. Results: The AB generated a 59-item-modified NA-SB, retaining most of the original NA-SB items and adding several more. Five items with concerns for relevance and/or clarity were revised to create the final 58-item-modified NA-SB. Priorities for implementation were identified by AB and clinician stakeholders. Conclusions: The modified NA-SB thoroughly reflects supportive care needs of our Midwestern AYA cancer survivors. When implemented, the tool may facilitate patient-care team communication and provide data to prioritize development of new supportive care resources. AYA cancer survivors have unique supportive care needs that are insufficiently addressed by current care models; using the modified NA-SB may help address those needs, leading to improved AYA outcomes.
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Supervivientes de Cáncer , Neoplasias , Humanos , Adolescente , Adulto Joven , Evaluación de Necesidades , Encuestas y Cuestionarios , Neoplasias/epidemiología , Oncología MédicaRESUMEN
BACKGROUND: CD40, a TNF receptor family member, is expressed by a variety of immune cells and is involved in the activation of both adaptive and innate immune responses. Here, we used quantitative immunofluorescence (QIF) to evaluate CD40 expression on the tumor epithelium of solid tumors in large patient cohorts of lung, ovarian, and pancreatic cancers. METHODS: Tissue samples from nine different solid tumors (bladder, breast, colon, gastric, head and neck, non-small cell lung cancer (NSCLC), ovarian, pancreatic and renal cell carcinoma), constructed in tissue microarray format, were initially assessed for CD40 expression by QIF. CD40 expression was then evaluated on the large available patient cohorts for three of the tumor types demonstrating high CD40 positivity rate; NSCLC, ovarian and pancreatic cancer. The prognostic impact of CD40 expression on tumor cells was also investigated. RESULTS: CD40 expression on tumor cells was found to be common, with 80% of the NSCLC population, 40% of the ovarian cancer population, and 68% of the pancreatic adenocarcinoma population displaying some degree of CD40 expression on cancer cells. All of three of these cancer types displayed considerable intra-tumoral heterogeneity of CD40 expression, as well as partial correlation between expression of CD40 on tumor cells and on surrounding stromal cells. CD40 was not found to be prognostic for overall survival in NSCLC, ovarian cancer, or pancreatic adenocarcinoma. CONCLUSIONS: The high percentage of tumor cells expressing CD40 in each of these solid tumors should be considered in the development of therapeutic agents designed to target CD40.
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Adenocarcinoma , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias Ováricas , Neoplasias Pancreáticas , Femenino , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Neoplasias Pancreáticas/genética , Antígenos CD40 , Neoplasias PancreáticasRESUMEN
Purpose: There are limited data to identify the best care model to support the vulnerable adolescent and young adult (AYA) oncology population. We sought to compare the impact of AYA physician visits versus interdisciplinary team (IDT) care on AYA-specific resource identification and utilization, as well as to provide a model of AYA oncology care implementation. Methods: We identified AYA-aged patients 15-39 years with a current or prior history of cancer seen by the University of Wisconsin Carbone Cancer Center (UWCCC) AYA Oncology Program between January 21, 2021 and May 27, 2021. Patients in this program have a one-on-one clinic visit with an AYA oncologist followed 4 days later by presentation at an AYA IDT meeting. We conducted retrospective chart review to quantify AYA-specific resource utilization before the AYA program visit, as well as novel resources identified by the AYA physician visit and the IDT meeting, and conducted a descriptive statistical analysis of the data. Results: We identified 35 patients seen by the UWCCC AYA Oncology Program. Before their AYA clinic visit, patients used an average of 2.51 AYA-specific services. An average of 4.45 novel resources was identified by the AYA Oncology Program per patient. This included an average of 2.54 and 1.91 additional resources identified per patient through the AYA physician visit and IDT meeting, respectively. The most common resource needs identified overall fell into the "other" category, consisting of a wide variety of resource domains (26/35) and peer support (27/35). Conclusions: Our data support increased resource identification through an AYA-specific care model. These objective data support the critical importance of AYA interdisciplinary care, as well as the use of an AYA IDT meeting model as a method to include interdisciplinary care in AYA programs despite possible resource constraints.
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While scholarly activity is recognized as critical in cancer education, there is an outstanding need for methods to define research learning competencies and tools for formal research productivity and competency assessment. We piloted and studied a novel educational initiative within the University of Wisconsin Hematology/Oncology fellowship program, establishing a professional learning community (PLC) of research mentors and developing a formative evaluation tool, a research portfolio. We developed a PLC engaged in reflective conversations about intended learning outcomes and effective instructional strategies. Subsequently, a research portfolio was piloted with four first-year Hematology/Oncology fellows at the start of the 2020 academic year in which trainees document, critically evaluate, and reflect upon the knowledge, skills, confidence, and productivity acquired during research training. We employed surveys to evaluate the initiative. Seven Hematology/Oncology fellows (7/12, 58%) completed pre-intervention and six-month interim evaluation surveys, with 43% (3/7) identifying an increased confidence in quality of research training strategies following the pilot initiation. All four first-year fellows that piloted the research portfolio (4/4, 100%) completed interim evaluation surveys that demonstrated benefits of the research portfolio including self-reflection and goal setting. Research portfolio scoring correlated with other markers of academic success, suggesting its potential to predict research success. Our data suggest that bringing together a community of research mentors to generate shared learning goals and develop the framework for a formative evaluation portfolio may meet critical needs research training needs in cancer education. Given promising results, we aim to create a new educational tool for research training.
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Hematología , Neoplasias , Humanos , Becas , Oncología Médica/educación , Curriculum , Hematología/educaciónRESUMEN
BACKGROUND: Perivascular epithelioid cell neoplasms (PEComas) are a diverse family of mesenchymal tumors with myomelanocytic differentiation that disproportionately affect women and can be associated with tuberous sclerosis (TS). Although mTOR inhibition is widely used as first-line treatment, it is unclear what genomic alterations exist in these tumors and how they influence the response to therapy. METHODS: This was a multicenter study conducted at five sites within the US. The data were collected from 1 January 2004 to 31 January 2021. We conducted a retrospective analysis to identify PEComa patients with next-generation sequencing (NGS) data and compared outcomes based on mutations. RESULTS: No significant differences in survival were identified between TSC-1 and TSC-2 mutated PEComa or TSC-1/-2 versus other mutations. No significant difference was seen in progression-free survival (PFS) after first-line therapy between mTOR inhibition versus other systemic therapies. CONCLUSIONS: We were unable to detect differences in survival based on genomic alterations or PFS between mTOR inhibition versus other systemic therapies. Future studies should seek to identify other drivers of TSC-1/-2 silencing that could predict response to mTOR inhibition.
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Neoplasias de Células Epitelioides Perivasculares , Femenino , Humanos , Mutación , Neoplasias de Células Epitelioides Perivasculares/genética , Neoplasias de Células Epitelioides Perivasculares/patología , Estudios Retrospectivos , Serina-Treonina Quinasas TOR/genéticaRESUMEN
Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised systemic therapy options for unresectable, progressive, or metastatic GIST based on mutational status, and updated recommendations for the management of GIST that develop resistance to specific tyrosine kinase inhibitors.
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Tumores del Estroma Gastrointestinal , Humanos , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/terapia , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Proteínas Proto-Oncogénicas c-kit/genética , MutaciónRESUMEN
Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as retroperitoneal/intra-abdominal STS, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis and treatment of retroperitoneal/intra-abdominal STS, outlines treatment recommendations, and reviews the evidence to support the guidelines recommendations.
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Sarcoma , Neoplasias de los Tejidos Blandos , Extremidades/patología , Humanos , Oncología Médica , Sarcoma/tratamiento farmacológico , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/terapiaRESUMEN
PURPOSE: Adolescent and young adult oncology programs are critical but exist primarily in academic centers, prompting potential disparities in care on the basis of patient residence. We studied the impact of residential location on supportive care receipt and treatment satisfaction in young adults (YAs) with cancer age 19-39 years treated at the University of Wisconsin Carbone Cancer Center (UWCCC). METHODS: YA patients with cancer age 19-39 years seen at UWCCC from March 30, 2019, to March 29, 2020, were sent a survey assessing supportive care receipt and satisfaction. Survey results were compared with retrospective chart review of YAs seen at UWCCC between April 1, 2011, and April 1, 2021. Data were categorized on the basis of residential location using distance from UWCCC and 2013 Rural-Urban Continuum Code (RUCC). RESULTS: Survey results were obtained for 145 YAs, including 29 from nonmetro RUCC (20.0%) and 81 living > 20 miles from UWCCC (55.9%). YAs from nonmetro locations had lower satisfaction with available treatments (79.3% v 91.4%, P = .005), and distant YAs living > 20 miles from UWCCC more frequently identified location as a barrier to supportive care receipt (35.6% v 15.8%, P = .02). Metro YAs more frequently listed fertility consultations as unavailable (38.0% v 16.0%, P = .04) in the survey despite chart review data showing higher rates of sexual health assessments (48.2% v 20.4%, P = .002) and fertility visits (29.6% v 18.5%, P = .18). CONCLUSION: We identified differences in both supportive care receipt and treatment satisfaction on the basis of residential location. These findings support the need for measures to successfully meet treatment and supportive care needs regardless of residential location.
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Neoplasias , Satisfacción Personal , Adolescente , Adulto , Humanos , Neoplasias/epidemiología , Neoplasias/terapia , Satisfacción del Paciente , Estudios Retrospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Expert knowledge is often shared among multidisciplinary academic teams at tumor boards (TBs) across the country, but these conversations exist in silos and do not reach the wider oncology community. OBJECTIVE: Using an oncologist-only question and answer (Q&A) website, we sought to document expert insights from TBs at National Cancer Institute-designated Comprehensive Cancer Centers (NCI-CCCs) to provide educational benefits to the oncology community. METHODS: We designed a process with the NCI-CCCs to document and share discussions from the TBs focused on areas of practice variation on theMednet, an interactive Q&A website of over 13,000 US oncologists. The faculty translated the TB discussions into concise, non-case-based Q&As on theMednet. Answers were peer reviewed and disseminated in email newsletters to registered oncologists. Reach and engagement were measured. Following each Q&A, a survey question asked how the TB Q&As impacted the readers' practice. RESULTS: A total of 23 breast, thoracic, gastrointestinal, and genitourinary programs from 16 NCI-CCC sites participated. Between December 2016 and July 2021, the faculty highlighted 368 questions from their TBs. Q&As were viewed 147,661 times by 7381 oncologists at 3515 institutions from all 50 states. A total of 277 (75%) Q&As were viewed every month. Of the 1063 responses to a survey question on how the Q&A affected clinicians' practices, 646 (61%) reported that it confirmed their current practice, 163 (20%) indicated that a Q&A would change their future practice, and 214 (15%) reported learning something new. CONCLUSIONS: Through an online Q&A platform, academics at the NCI-CCCs share knowledge outside the walls of academia with oncologists across the United States. Access to up-to-date expert knowledge can reassure clinicians' practices, significantly impact patient care in community practices, and be a source of new knowledge and education.
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BACKGROUND: Sarcomas are rare diagnoses but are seen with relative frequency in adolescents and young adults and thus can present in pregnancy. We sought to study the administration of anthracyclines and/or ifosfamide in pregnancy-associated sarcomas. PATIENTS AND METHODS: We conducted a multi-institutional retrospective study, identifying sarcoma patients who received anthracyclines and/or ifosfamide during pregnancy. Chart review identified variables related to demographics, cancer diagnosis, therapies, and outcome of the patient and fetus. Wilcoxon rank-sum test compared two independent samples. RESULTS: We identified 13 patients at seven institutions with sarcoma who received anthracyclines and/or ifosfamide during pregnancy, including four bone sarcomas and nine soft tissue sarcomas diagnosed at a mean gestational age of 16.7 ± 5.9 weeks. Only nine patients had live births (9/13, 69.2%), with mean gestational age of 30.8 ± 3.8 weeks at delivery. The four patients with pregnancy loss all received both doxorubicin and ifosfamide, with chemotherapy initiated at 15.5 weeks as compared with 21.3 weeks for those patients with live births (p = 0.016). CONCLUSION: In this multi-institutional study of sarcoma chemotherapy regimens administered during pregnancy, we found a high rate of fetal demise that was seen only in patients receiving both doxorubicin and ifosfamide and statistically more likely with chemotherapy initiation earlier in the second trimester. While limited by a small sample size, our study represents the largest study of sarcoma patients that received anthracyclines and/or ifosfamide in pregnancy thus far reported and supports development of an international registry to study concerns raised by our study.
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Sarcoma , Neoplasias de los Tejidos Blandos , Adolescente , Antraciclinas/efectos adversos , Antibióticos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Doxorrubicina/uso terapéutico , Femenino , Humanos , Ifosfamida/efectos adversos , Lactante , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Resultado del Tratamiento , Adulto JovenRESUMEN
Tissue-agnostic drug development is a major step forward in offering treatment options for rare tumors. Sarcomas are heterogeneous rare malignancies with more than 100 subtypes. Recent failure of Phase III trials, nonbiomarker-driven clinical trials, and rarity hamper developmental therapeutics in sarcomas. Since a 'one-size-fits-all' approach continues to be the standard of care, tissue-agnostic approvals assume significance in sarcomas. In this review, we focus on the clinical evidence of recent drug approvals for neurotrophic tyrosine receptor kinase (NTRK) fusion, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) phenotype, and tumor mutation burden-high (TMB-H) status in the context of sarcomas, and the future landscape of tissue-agnostic targets, such as rearranged during transfection (RET), fibroblast growth factor receptor (FGFR), and neuregulin-1 (NRG1).
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Sarcoma , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Fusión Génica , Humanos , Inestabilidad de Microsatélites , Proteínas Tirosina Quinasas Receptoras/genética , Sarcoma/diagnóstico , Sarcoma/tratamiento farmacológico , Sarcoma/genéticaRESUMEN
BACKGROUND: Given a link between sarcomas and hereditary cancer predisposition syndromes, including Li-Fraumeni syndrome, the consideration for genetic counseling is recommended for all adolescent and young adult (AYA) patients diagnosed with sarcoma. The aim of this study was to evaluate factors influencing genetic consultations in AYA patients with sarcoma at the University of Wisconsin (UW). METHODS: A retrospective chart review was performed on AYA patients diagnosed with sarcoma between the ages of 15 and 39 years who were seen at least once between 2015 to 2019 at UW. Our chart review identified discussions regarding genetics, referrals to genetics, genetic consultations, and results of genetic testing. Variables hypothesized to affect patient referrals for genetic consultation were identified a priori. Descriptive statistical methods and a univariate analysis were used to identify patient characteristics associated with genetic counseling referral. RESULTS: We identified 87 AYA patients with sarcoma. Only 19 (22%) of these patients had documentation of a discussion about genetics, 15 (17%) of whom were subsequently referred for genetic consultation. Of these 15 patients, 9 (60%) were seen in consultation. All 9 patients seen by genetics underwent genetic testing, with 4 (44%) of these patients having identified heritable cancer predisposition syndromes. Likelihood for genetics referral was linked most strongly to documented genetics discussion with an oncology provider (P<.001). CONCLUSIONS: Despite the recommendation for consideration for genetic counseling in AYA patients with sarcoma, <25% of such patients in our study had a documented discussion about genetics. Supporting this need, all referred patients met criteria for genetic testing, and 44% of tested patients were found to have a heritable cancer predisposition syndrome. These data support the initial conversation by a provider as critical to genetic referral and suggest the need for more specific national recommendations for the genetic evaluation of all AYA patients with sarcoma.
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PURPOSE: Given the occurrence of cancer during a complex developmental time, adolescent and young adult (AYA) patients have unique psychosocial needs that necessitate supportive care, which is optimally provided using National Comprehensive Cancer Network (NCCN) AYA guidelines. We sought to explore compliance with NCCN AYA guidelines and compare with oncology providers' perceptions of AYA care needs. METHODS: Retrospective chart reviews of AYA patients (15-39 years at time of cancer diagnosis) with sarcoma seen at least once in 2019 at the University of Wisconsin identified documentation of discussions deemed critical per NCCN AYA guidelines. As per the ASCO Quality Oncology Practice Initiative certification, we considered a threshold of these factors being discussed 75% of the time or higher to be compliant. Compliance was compared with an electronic survey of University of Wisconsin oncology providers regarding AYA patient needs, with items determined to have adequate resources if noted sufficient by at least 75% of providers. RESULTS: We identified 43 AYA patients with sarcoma. Less than 75% of patients had documentation of discussion of contraception, sexual health, fertility, finances, genetics, social work referral, and clinical trials indicating noncompliance with NCCN guidelines. Surveys, completed by 38 oncology providers, showed significant discordance between providers' perceptions of AYAs' access to resources and providers' documented discussions of supportive care resources. CONCLUSION: Disparities between oncology provider assessment of AYA care needs and documentation of critical components of AYA patient care demonstrate the need for novel tools to evaluate AYA care needs beyond provider assessments.
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Sarcoma , Neoplasias de los Tejidos Blandos , Adolescente , Adulto , Documentación , Humanos , Oncología Médica , Estudios Retrospectivos , Sarcoma/diagnóstico , Sarcoma/terapia , Adulto JovenRESUMEN
PURPOSE: Metastatic phyllodes tumors of the breast (MPT) are rare breast neoplasms, limiting development of standardized treatment approaches. We sought to characterize the largest group of MPT thus far reported, evaluating systemic therapy outcomes. METHODS: Adult patients diagnosed with MPT between 1993 and 2015 and followed at MD Anderson Cancer Center were selected for retrospective chart review. Systemic therapy was sorted into: adriamycin/ifosfamide (AI), other anthracycline regimens, other ifosfamide regimens, gemcitabine-based regimens, and other. Given one patient may have received more than one regimen, we assumed that the effects of each regimen were independent from previous therapy. Median overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Log-rank test was performed to evaluate the difference in OS between patient characteristics groups, and the differences in PFS between the five chemotherapy regimens. RESULTS: We identified 50 MPT patients, with 31 patients receiving 61 systemic regimens. Median OS was 10.7 months (95% CI: 8.67, 16.5). AI had a PFS of 9.10 months (95% CI: 5.03, 14.2), other ifosfamide regimens had a PFS of 5.10 months (95% CI: 0.67, 12.1), other anthracycline regimens had a PFS of 3.65 months (95% CI: 1.17, 7.90), gemcitabine-based regimens had a PFS of 2.80 months (95% CI: 1.83, 4.60), and other regimens had a PFS of 1.67 months (95% CI: 1.13, 7.77). CONCLUSION: MPT patients are a unique population with limited characterization to date. Our study demonstrates activity of multiple sarcoma-directed chemotherapy regimens, with ifosfamide-containing regimens having the longest PFS.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mama , Neoplasias de la Mama/tratamiento farmacológico , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OPINION STATEMENT: Malignant peripheral nerve sheath tumors (MPNSTs) are rare mesenchymal neoplasms that represent a profound therapeutic challenge due to their high proclivity for recurrence and metastasis and relatively poor response to systemic therapy regimens. While our understanding of the pathophysiology of MPNST is growing, including loss of the tumor suppressor gene neurofibromin and subsequent activation of the Ras pathway, targeted therapy to modify the poor prognosis seen in MPNST patients has thus far been without success. Correspondingly, MPNST patients are treated as per soft tissue sarcoma treatment algorithms with anthracycline-based therapy as the front-line therapy of choice for patients with unresectable, locally advanced, or metastatic MPNST. Beyond first-line anthracycline-based therapy, other standard cytotoxic chemotherapy agents used in advanced MPNST include the alkylating agent ifosfamide and the topoisomerase II inhibitor etoposide. Notably, soft tissue sarcoma regimens are used in MPNST despite distinct systemic therapy sensitivity and prognosis. This is particularly notable for neurofibromatosis type 1 (NF1)-associated MPNST, which is associated with poorer response to systemic therapy and prognosis than sporadic MPNST. As such, NF1-associated MPNST is a particular area in need of novel therapeutic strategies. Given the lack of benefit in the targeting of unique aspects of MPNST disease biology thus far, pre-clinical studies to identify novel rational therapies are critical to inform future clinical trials.
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Neoplasias de la Vaina del Nervio/diagnóstico , Neoplasias de la Vaina del Nervio/terapia , Biomarcadores de Tumor , Toma de Decisiones Clínicas , Terapia Combinada , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Predisposición Genética a la Enfermedad , Humanos , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias de la Vaina del Nervio/etiología , Neoplasias de la Vaina del Nervio/mortalidad , Pronóstico , Resultado del TratamientoRESUMEN
The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for gastrointestinal stromal tumors (GISTs); reconception of the management of desmoid tumors; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of radiation therapy for soft tissue sarcomas.
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Sarcoma , Neoplasias de los Tejidos Blandos , Extremidades , Tumores del Estroma Gastrointestinal , Humanos , Guías de Práctica Clínica como Asunto , Neoplasias Retroperitoneales , Sarcoma/diagnóstico , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/terapiaRESUMEN
BACKGROUND: Cytotoxic chemotherapy remains the standard of care first-line treatment for advanced and metastatic soft-tissue sarcomas (STSs). Certain patients may not be chemotherapy candidates based upon age or co-morbidities, leaving limited treatment options. Pazopanib is a multi-targeted tyrosine kinase inhibitor that is FDA-approved for metastatic STS after the first line. We proposed a phase II study evaluating pazopanib as a first-line agent in patients with advanced disease who are deemed not to be candidates for chemotherapy. METHODS: Eligible patients were at least 18 years old, not candidates for chemotherapyand were treatment naive. Pazopanib was titrated from 200 mg twice daily to a goal of 800 mg daily. The primary end point was the clinical benefit rate (CBR) (CBR = completed response + partial response + stable disease per Response Evaluation Criteria in Solid Tumours [RECIST 1.1]) at 16 weeks. The sample size of 56 evaluable patients was calculated to provide 80% power to test a hypothesised CBR of ≥35% against an unfavourable CBR of ≤20%. If ≥ 17 patients achieved benefit, the null CBR of 20% would be rejected at a nominal 5% alpha level. Secondary end points included progression-free survival (PFS), overall survival (OS), quality of life and serum biomarkers. FINDINGS: Fifty-six patients were enrolled from May 2015 to February 2019 and are included in the intention-to-treat analysis. Median PFS was 3.67 (2.62-7.25) months. Median OS was 14.16 (95% confidence interval [CI]: 8.4-NR) months, CBR = 39.29% (22/56) (CI = 0.265-0.533, p = 0.0007). No new or unexpected adverse events were seen. The most common grade I-II events were diarrhoea, nausea and fatigue. The most common grade III-IV events were hypertension and liver function test abnormalities. INTERPRETATION: These data suggest that there is a benefit to front-line pazopanib in patients with STS who are not candidates for cytotoxic chemotherapy.
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Pirimidinas/uso terapéutico , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Anciano , Femenino , Humanos , Indazoles , Masculino , Metástasis de la Neoplasia , Supervivencia sin Progresión , Pirimidinas/farmacología , Sarcoma/mortalidad , Sarcoma/patología , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Sulfonamidas/farmacologíaRESUMEN
Distinguishing well-differentiated liposarcoma (WDLPS) from dedifferentiated liposarcoma (DDLPS) is essential given distinct treatment paradigms and chemosensitivity. Percutaneous biopsy has a low sensitivity for detecting DDLPS. We sought to identify the diagnostic utility of positron emission tomography/computed tomography (PET/CT) in identifying WDLPS versus DDLPS. An independent radiologist reviewed PET/CT images to identify target lesions and determine the maximum standardized uptake value (SUVmax). An independent pathologist review confirmed WDLPS or DDLPS histology. A binary cutoff point of SUVmax was identified using a classification and regression trees (CART) algorithm. We identified 20 patients with WDLPS or DDLPS with 26 PET/CTs performed for separate recurrences that were followed by surgical sampling. Of the 26 records, 12 were DDLPS (46%) and 14 were WDLPS (54%). Patients with DDLPS had significantly higher SUVmax than those with WDLPS (p value = 0.0035). A SUVmax of 4 was identified as the cutoff point. Using this cutoff, the sensitivity of SUVmax identifying a case as DDLPS was 83.3% (95% CI: 51.6%, 97.9%) and the specificity was 85.7% (95% CI: 57.2%, 98.2%). PET/CT is a sensitive and specific diagnostic tool to identify the presence of dedifferentiation within the tumor.
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BACKGROUND: Cancer screening is chiefly performed by primary care providers (PCPs) who rely on organizational screening guidelines. These guidelines provide evidence-based recommendations; however, they are often without unanimity leading to divergent screening recommendations. OBJECTIVE: Due to the high incidence of breast cancer, the availability of screening methods, and the presence of multiple incongruent guideline recommendations, we sought to understand breast cancer screening practices in Wisconsin to identify patterns that would allow us to improve evidence-based screening adherence. METHODS: A 46-question survey on breast cancer screening beliefs and practices for average-risk women was sent to healthcare providers in Wisconsin in 2018, who provided cancer screening services to women. Providers included physicians, nurse practitioners (NPs), physician assistants (PAs), and midwives. RESULTS: A total of 295 people responded to the survey, for a response rate of 28.6%. Most respondents were physicians (64.1%), followed by NPs (25.7%), PAs (5.3%), and midwives (1.5%). Of physicians, most practiced family medicine (65.3%), followed by internal medicine (25.3%) and gynecology (9.4%). The United States Preventive Services Task Force (USPSTF) was reported as being "very influential" for 60.5% of providers, followed by the American Cancer Society at 46.8%. For patients 40-49 years old, 75.6% of providers performed clinical breast exams and 58.5% recommended self-breast exams; these numbers increased for women 50+ years old to 78.7% and 61.2%, respectively. Mammography was more likely to be recommended annually for women aged 40-49 rather than biennially by non-physician clinicians compared to physicians (p < .001). CONCLUSIONS: PCPs in Wisconsin continue to overestimate the efficacy of clinical and self-breast exams as well as overuse these in clinical practice. Providers find multiple screening guidelines influential but favor the USPSTF; however, these guidelines are frequently not being followed. Further research needs to be done to investigate the lack of national guideline adherence by providers to improve compliance with evidence-based screening recommendations.