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1.
BMJ Case Rep ; 16(11)2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37967927

RESUMO

Hypercalcaemia is recognised as the most common oncological metabolic emergency, with several proposed underlying mechanisms. Nevertheless, hypercalcaemia has been rarely reported as a complication in patients with gastrointestinal stromal tumours (GISTs). GISTs are uncommon mesenchymal tumours of the gastrointestinal tract. There are only nine previous cases of hypercalcaemia occurring in patients with GIST reported in the literature. We report a case of a man in his 70s with a background of metastatic GIST on fourth-line treatment. The patient presented with new hypercalcaemia and acute kidney injury. Despite medical management, his calcium remained elevated and he deteriorated secondary to significant disease progression.


Assuntos
Tumores do Estroma Gastrointestinal , Hipercalcemia , Masculino , Humanos , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/patologia , Hipercalcemia/complicações , Progressão da Doença
2.
J Med Case Rep ; 17(1): 419, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37798760

RESUMO

BACKGROUND: This case reports the synchronous diagnosis of two rare unrelated diseases; leiomyosarcoma and tenosynovial giant cell tumor of the knee. It focuses on the challenges of diagnosing tenosynovial giant cell tumor, including cognitive biases in clinical medicine that delay diagnosis. It also demonstrates the pathogenic etiology of tenosynovial giant cell tumor, evidenced by the transient deterioration of the patients' knee symptoms following the administration of prophylactic granulocyte colony-stimulating factor given as part of the chemotherapeutic regime for leiomyosarcoma. CASE PRESENTATION: A 37-year-old Caucasian man presented with a left groin lump and left knee pain with swelling and locking. Investigations including positron emission tomography-computed tomography and biopsy revealed leiomyosarcoma in a lymph node likely related to the spermatic cord, with high-grade uptake in the left knee that was presumed to be the primary site. His knee symptoms temporarily worsened each time granulocyte colony-stimulating factor was administered with each cycle of chemotherapy for leiomyosarcoma to help combat myelosuppressive toxicity. Subsequent magnetic resonance imaging and biopsy of the knee confirmed a tenosynovial giant cell tumor. His knee symptoms relating to the tenosynovial giant cell tumor improved following the completion of his leiomyosarcoma treatment. CONCLUSIONS: Tenosynovial giant cell tumor remains a diagnostic challenge. We discuss the key clinical features and investigations that aid prompt diagnosis. The National Comprehensive Cancer Network clinical practice guidelines for soft tissue sarcoma have recently been updated to include the pharmacological management of tenosynovial giant cell tumor. Our case discussion provides an up-to-date review of the evidence for optimal management of patients with tenosynovial giant cell tumor, with a particular focus on novel pharmacological options that exploit underlying pathogenesis.


Assuntos
Tumor de Células Gigantes de Bainha Tendinosa , Leiomiossarcoma , Masculino , Humanos , Adulto , Leiomiossarcoma/patologia , Tumor de Células Gigantes de Bainha Tendinosa/diagnóstico por imagem , Tumor de Células Gigantes de Bainha Tendinosa/patologia , Articulação do Joelho/patologia , Joelho/patologia , Fator Estimulador de Colônias de Granulócitos
3.
Proc Biol Sci ; 290(2007): 20231466, 2023 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-37752838

RESUMO

Diving animals must sustain high activity with limited O2 stores to successfully capture prey. Studies suggest that increasing body O2 stores supports breath-hold diving, but less is known about metabolic specializations that underlie underwater locomotion. We measured maximal activities of 10 key enzymes in locomotory muscles (gastrocnemius and pectoralis) to identify biochemical changes associated with diving in pathways of oxidative and substrate-level phosphorylation and compared them across three groups of ducks-the longest diving sea ducks (eight spp.), the mid-tier diving pochards (three spp.) and the non-diving dabblers (five spp.). Relative to dabblers, both diving groups had increased activities of succinate dehydrogenase and cytochrome c oxidase, and sea ducks further showed increases in citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase (HOAD). Both diving groups had relative decreases in capacity for anaerobic metabolism (lower ratio of lactate dehydrogenase to CS), with sea ducks also showing a greater capacity for oxidative phosphorylation and lipid oxidation (lower ratio of pyruvate kinase to CS, higher ratio of HOAD to hexokinase). These data suggest that the locomotory muscles of diving ducks are specialized for sustaining high rates of aerobic metabolism, emphasizing the importance of body O2 stores for dive performance in these species.


Assuntos
Patos , Locomoção , Animais , Metabolismo dos Lipídeos , Anaerobiose , Músculos Peitorais
4.
Eur J Cancer ; 178: 216-226, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36470093

RESUMO

BACKGROUND: Adolescent and young adult (AYA) patients with cancer are poorly recruited to molecularly targeted trials and have not witnessed the advances in cancer treatment and survival seen in other age groups. We report here a pan-European proof-of-concept study to identify actionable alterations in some of the worst prognosis AYA cancers: bone and soft tissue sarcomas. DESIGN: Patients aged 12-29 years with newly diagnosed or recurrent, intermediate or high-grade bone and soft tissue sarcomas were recruited from six European countries. Pathological diagnoses were centrally reviewed. Formalin-fixed tissues were analysed by whole exome sequencing, methylation profiling and RNA sequencing and were discussed in a multidisciplinary, international molecular tumour board. RESULTS: Of 71 patients recruited, 48 (median 20 years, range 12-28) met eligibility criteria. Central pathological review confirmed, modified and re-classified the diagnosis in 41, 3, and 4 cases, respectively. Median turnaround time to discussion at molecular tumour board was 8.4 weeks. whole exome sequencing (n = 48), methylation profiling (n = 44, 85%) and RNA sequencing (n = 24, 50%) led to therapeutic recommendations for 81% patients, including 4 with germ line alterations. The most common were for agents targeted towards tyrosine kinases (n = 20 recommendations), DNA repair (n = 18) and the PI3K/mTOR/AKT pathway (n = 15). Recommendations were generally based on weak evidence such as activity in a different tumour type (n = 68, 61%), reflecting the dearth of relevant molecular clinical trial data in the same tumour type. CONCLUSIONS: We demonstrate here that comprehensive molecular profiling of AYA patients' samples is feasible and deliverable in a European programme.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Adolescente , Humanos , Adulto Jovem , Europa (Continente) , Sequenciamento do Exoma , Prognóstico , Sarcoma/genética , Sarcoma/terapia , Estudo de Prova de Conceito
5.
J R Coll Physicians Edinb ; 52(2): 138-141, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-36146991

RESUMO

Hypercalcaemia is common in patients with malignancy, but is rare in seminoma with only eight cases reported in the literature. We present an unusual case of a 36-year-old man who presented with hypercalcaemia and stage 3 acute kidney injury. He presented initially with headache and malaise, and was found to have markedly deranged blood tests. He underwent a renal biopsy before imaging confirmed an unexpected large abdominal mass, which was confirmed histologically to be a seminoma. He was referred to a tertiary oncology centre, and underwent emergency chemotherapy and radical resection with no evidence of recurrence to this date and with return to normocalcaemia.


Assuntos
Injúria Renal Aguda , Hipercalcemia , Seminoma , Neoplasias Testiculares , Injúria Renal Aguda/etiologia , Adulto , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Masculino , Seminoma/complicações , Seminoma/diagnóstico , Seminoma/patologia , Neoplasias Testiculares/complicações , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patologia
6.
Glob Pediatr Health ; 9: 2333794X221105261, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35747898

RESUMO

Disposable baby wipes manufactured by Procter & Gamble, soft sheets bearing lotion that is balanced to maintain natural skin pH, are convenient for cleaning the diaper area and a quick cleanup on baby's face and hands. Objective: Develop a rigorous safety assessment process to ensure that baby wipes are safe and gentle to skin. This process is built-in from the start of product research and development. Methods: A systematic, iterative approach that includes (1) exposure-based safety assessment of all raw materials for systemic and local effects, which are consistent with established risk assessment paradigms; (2) when needed, testing of finished wipes in in vitro and/or clinical studies for skin and eye irritation, contact sensitization, or mechanical effects on skin in comparison to benchmark products that have a long history of wipe safety in marketplace; (3) prospective and randomized in-use studies in babies; and (4) in-market monitoring that is an integral part of the on-going product safety assessment. Results: Individual approaches and/or their combination show mildness of the test wipes. Further, in-market monitoring is testimony to baby skin compatibility of baby wipes. Conclusion: The approaches that have been developed demonstrate the skin compatibility and/or benefits of baby wipes relative to other modes of cleaning if needed. This article describes our safety assurance program, exposure-based safety assessment, and the range of robust testing strategies and approaches that can be employed to assure the safety of baby wipes.

7.
Int J Radiat Oncol Biol Phys ; 113(4): 825-832, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35461737

RESUMO

PURPOSE: Radiation therapy is a possible treatment strategy for patients with testicular seminoma after orchiectomy in clinical stage I or II disease. Little is known about the outcome of patients who experience a relapse after radiation therapy. METHODS AND MATERIALS: Data from 61 patients who relapsed after adjuvant or curative radiation therapy from 17 centers in 11 countries were collected and retrospectively analyzed. Primary outcomes were disease-free and overall survival. Secondary outcomes were time to relapse, stage at relapse, treatment for relapse, and rate of febrile neutropenia during chemotherapy for relapse. RESULTS: With a median follow-up of 9.9 years (95% confidence interval [CI], 7.5-10.9), we found a 5-year disease-free survival of 90% (95% CI, 79-95) and a 5-year overall survival of 98% (95% CI, 89-100). Sixty-six percent of patients had stage III disease at time of relapse and 93% of patients fell into the good prognosis group per the International Germ Cell Cancer Collaborative Group classification. The median time to relapse after radiation therapy was 15.6 months (95% CI, 12-23). Twenty-two (36%) patients relapsed more than 2 years after radiation therapy and 7 (11.5%) patients relapsed more than 5 years after radiation therapy. One-third of relapses was detected owing to patients' symptoms, whereas two-thirds of relapses were detected during routine follow-up. The majority (93%) of cases were treated with cisplatin-based chemotherapy. The rate of febrile neutropenia during chemotherapy was 35%. Five patients experienced a second relapse. At last follow-up, 55 patients (90%) were alive without disease. Only 1 patient died owing to disease progression. CONCLUSIONS: Cisplatin-based chemotherapy for patients with seminoma who have relapsed after treatment with radiation therapy alone leads to excellent outcomes. Patients and physicians should be aware of possible late relapses after radiation therapy.


Assuntos
Neutropenia Febril , Seminoma , Neoplasias Testiculares , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Progressão da Doença , Neutropenia Febril/tratamento farmacológico , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia/radioterapia , Estadiamento de Neoplasias , Orquiectomia , Estudos Retrospectivos , Seminoma/tratamento farmacológico , Seminoma/radioterapia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/radioterapia
8.
J Clin Oncol ; 40(22): 2468-2478, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35298280

RESUMO

PURPOSE: Survival in stage I seminoma is almost 100%. Computed tomography (CT) surveillance is an international standard of care, avoiding adjuvant therapy. In this young population, minimizing irradiation is vital. The Trial of Imaging and Surveillance in Seminoma Testis (TRISST) assessed whether magnetic resonance images (MRIs) or a reduced scan schedule could be used without an unacceptable increase in advanced relapses. METHODS: A phase III, noninferiority, factorial trial. Eligible participants had undergone orchiectomy for stage I seminoma with no adjuvant therapy planned. Random assignment was to seven CTs (6, 12, 18, 24, 36, 48, and 60 months); seven MRIs (same schedule); three CTs (6, 18, and 36 months); or three MRIs. The primary outcome was 6-year incidence of Royal Marsden Hospital stage ≥ IIC relapse (> 5 cm), aiming to exclude increases ≥ 5.7% (from 5.7% to 11.4%) with MRI (v CT) or three scans (v 7); target N = 660, all contributing to both comparisons. Secondary outcomes include relapse ≥ 3 cm, disease-free survival, and overall survival. Intention-to-treat and per-protocol analyses were performed. RESULTS: Six hundred sixty-nine patients enrolled (35 UK centers, 2008-2014); mean tumor size was 2.9 cm, and 358 (54%) were low risk (< 4 cm, no rete testis invasion). With a median follow-up of 72 months, 82 (12%) relapsed. Stage ≥ IIC relapse was rare (10 events). Although statistically noninferior, more events occurred with three scans (nine, 2.8%) versus seven scans (one, 0.3%): 2.5% absolute increase, 90% CI (1.0 to 4.1). Only 4/9 could have potentially been detected earlier with seven scans. Noninferiority of MRI versus CT was also shown; fewer events occurred with MRI (two [0.6%] v eight [2.6%]), 1.9% decrease (-3.5 to -0.3). Per-protocol analyses confirmed noninferiority. Five-year survival was 99%, with no tumor-related deaths. CONCLUSION: Surveillance is a safe management approach-advanced relapse is rare, salvage treatment successful, and outcomes excellent, regardless of imaging frequency or modality. MRI can be recommended to reduce irradiation; and no adverse impact on long-term outcomes was seen with a reduced schedule.


Assuntos
Seminoma , Neoplasias Testiculares , Quimioterapia Adjuvante , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Estadiamento de Neoplasias , Orquiectomia , Seminoma/tratamento farmacológico , Seminoma/terapia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/cirurgia
10.
JCO Glob Oncol ; 7: 1067-1073, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34191537

RESUMO

PURPOSE: In Scotland, approximately 350 sarcoma cases are diagnosed per year and treated in one of the five specialist centers. Many patients are required to travel long distances to access specialist care. The COVID-19 pandemic brought a number of rapid changes into the care for patients with cancer, with increasing utilization of telemedicine. We aimed to evaluate how the utilization of telemedicine affects professionals and patients across Scotland and care delivery, at the Beatson West of Scotland Cancer Centre Sarcoma Unit. METHODS: Between June 8 and August 25, 2020, we invited patients and professional sarcoma multidisciplinary team members to participate in separate online anonymous survey questionnaires, to assess their attitudes toward telemedicine. Data were extracted, and descriptive statistics were performed. RESULTS: Patient satisfaction (n = 64) with telemedicine was high (mean = 9.4/10) and comparable with traditional face-to-face appointments (mean = 9.5/10). Patients were receptive to the use of telemedicine in certain situations, with patients strongly opposed to being told bad news via telemedicine (88%). Providers recommended the use of telemedicine in certain patient populations and reported largely equivalent workloads when compared with traditional consultations. Providers reported that telemedicine should be integrated into regular practice (66%), with patients echoing this indicating a preference for a majority of telemedicine appointments (57%). CONCLUSION: Telemedicine in sarcoma care is favorable from both clinician and patient perspectives. Utilization of telemedicine for patients with rare cancers such as sarcomas is an innovative approach to the delivery of care, especially considering the time and financial pressures on patients who often live a distance away from specialist centers. Patients and providers are keen to move toward a more flexible, mixed system of care.


Assuntos
COVID-19 , Sarcoma , Telemedicina , Humanos , Pandemias , Satisfação do Paciente , SARS-CoV-2 , Sarcoma/epidemiologia , Sarcoma/terapia , Escócia/epidemiologia
11.
J R Coll Physicians Edinb ; 51(1): 53-57, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33877136

RESUMO

Testicular cancer is the most common malignancy in young men. We discuss four cases of germ cell tumours (GCTs) presenting to general practitioners and physicians where there were notable preventable delays in the diagnosis and management. This diagnostic delay is associated with a more advanced stage of disease, and subsequent increased treatment-related morbidity and decreased survival. Our series highlights the variety of ways in which GCTs may present and we discuss the importance of prompt diagnosis through a thorough history and examination, early measurement of serum tumour markers and appropriate multidisciplinary team discussion. GCTs are highly curable cancers in the majority of patients and delays in management can, therefore, have devastating consequences.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Biomarcadores Tumorais , Diagnóstico Tardio , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia
12.
J Plast Reconstr Aesthet Surg ; 74(6): 1180-1192, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33308991

RESUMO

Currently, there are no comprehensive breast sarcoma guidelines in the UK. There is therefore a need for guidelines to clarify surgical management, which we have based on data from our regional audit, current evidence, and consensus between West of Scotland Breast Cancer and Scottish Sarcoma Managed Clinical Networks. Methods and results: From 2007 to 2019, 46 patients were treated with breast sarcoma in the West of Scotland. Sarcoma Centre versus Peripheral Hospitals: Incomplete excision rate was 0% at sarcoma centre and 50% at peripheral hospitals (p = 0.0002, Odds Ratio 43). For angiosarcoma, 0% positive margin at the sarcoma centre versus 62.5% at the peripheral unit (p = 0.0036, odds ratio 39.3). Tumours treated at the sarcoma centre were larger than those treated at peripheral hospitals (92.5 versus 39.7 mm, p = 0.0009). WLE (wide local excision) versus mastectomy: Out of eight WLE patients, seven (87.5%) had positive margins, with 6 of these patients proceeding to mastectomy (i.e. 75% WLE patients ultimately had a mastectomy). The positive margin rate was significantly higher in WLE (87.5%) than in mastectomy (10.3%) (p = 0.0001, odds ratio 60.7). Survival: No difference was noted between the sarcoma centre and peripheral hospitals for overall survival (p = 0.43), stratified for tumours <5 cm (p = 0.16), and disease-free survival (p = 0.45). Conclusions: Our data strongly suggest that specific guidelines are needed for breast sarcoma, and that managing these patients according to breast carcinoma protocols in peripheral hospitals is sub-optimal. We recommend centralisation of breast sarcoma patient care to a specialist sarcoma centre, with WLE not recommended as a firstline surgical option given both the high rates of incomplete excision and subsequent need for completion mastectomy.


Assuntos
Neoplasias da Mama , Protocolos Clínicos/normas , Mastectomia , Guias de Prática Clínica como Assunto , Sarcoma , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Necessidades e Demandas de Serviços de Saúde , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Humanos , Masculino , Margens de Excisão , Mastectomia/efeitos adversos , Mastectomia/métodos , Mastectomia/estatística & dados numéricos , Sistema de Registros , Sarcoma/patologia , Sarcoma/cirurgia , Escócia/epidemiologia
13.
JACC CardioOncol ; 2(3): 443-455, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33043304

RESUMO

BACKGROUND: Cisplatin-based chemotherapy increases the risk of cardiovascular and renal disease. OBJECTIVES: We aimed to define the time course, pathophysiology, and approaches to prevent cardiovascular disease associated with cisplatin-based chemotherapy. METHODS: Two cohorts of patients with a history of testicular cancer (n = 53) were recruited. Cohort 1 consisted of 27 men undergoing treatment with: 1) surveillance; 2) 1 to 2 cycles of bleomycin, etoposide, and cisplatin (BEP) chemotherapy (low-intensity cisplatin); or 3) 3 to 4 cycles of BEP (high-intensity cisplatin). Endothelial function (percentage flow-mediated dilatation) and cardiovascular biomarkers were assessed at 6 visits over 9 months. Cohort 2 consisted of 26 men previously treated 1 to 7 years ago with surveillance or 3 to 4 cycles BEP. Vasomotor and fibrinolytic responses to bradykinin, acetylcholine, and sodium nitroprusside were evaluated using forearm venous occlusion plethysmography. RESULTS: In cohort 1, the percentage flow-mediated dilatation decreased 24 h after the first cisplatin dose in patients managed with 3 to 4 cycles BEP (10.9 ± 0.9 vs. 16.7 ± 1.6; p < 0.01) but was unchanged from baseline thereafter. Six weeks after starting 3 to 4 cycles BEP, there were increased serum cholesterol levels (7.2 ± 0.5 mmol/l vs. 5.5 ± 0.2 mmol/l; p = 0.01), hemoglobin A1c (41.8 ± 2.0 mmol/l vs. 35.5 ± 1.2 mmol/l; p < 0.001), von Willebrand factor antigen (62.4 ± 5.4 mmol/l vs. 45.2 ± 2.8 mmol/l; p = 0.048) and cystatin C (0.91 ± 0.07 mmol/l vs. 0.65 ± 0.09 mmol/l; p < 0.01). In cohort 2, intra-arterial bradykinin, acetylcholine, and sodium nitroprusside caused dose-dependent vasodilation (p < 0.0001). Vasomotor responses, endogenous fibrinolytic factor release, and cardiovascular biomarkers were not different in patients managed with 3 to 4 cycles of BEP versus surveillance. CONCLUSIONS: Cisplatin-based chemotherapy induces acute and transient endothelial dysfunction, dyslipidemia, hyperglycemia, and nephrotoxicity in the early phases of treatment. Cardiovascular and renal protective strategies should target the early perichemotherapy period. (Clinical Characterisation of the Vascular Effects of Cis-platinum Based Chemotherapy in Patients With Testicular Cancer [VECTOR], NCT03557177; Intermediate and Long Term Vascular Effects of Cisplatin in Patients With Testicular Cancer [INTELLECT], NCT03557164).

15.
BMJ Open Qual ; 9(1)2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32213550

RESUMO

Testicular cancer is the most common malignancy in young adult men. The prognosis is excellent in limited disease and cure is possible even in advanced disease. Quality performance indicators (QPI) are used in many developed countries as a measure of healthcare performance. We report and discuss the development of a national set of QPIs in Scotland for testicular cancer as a method of gathering demographic data and driving improvement in nationwide testicular cancer outcomes.


Assuntos
Melhoria de Qualidade , Indicadores de Qualidade em Assistência à Saúde/tendências , Neoplasias Testiculares/diagnóstico , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde/normas , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Escócia , Medicina Estatal/normas , Medicina Estatal/tendências , Neoplasias Testiculares/terapia
16.
BMJ Case Rep ; 13(2)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32060110

RESUMO

Sinonasal malignancies are a very rare diagnosis. We present a unique case of a 32-year-old man who presented with symptoms of worsening sinusitis and periorbital cellulitis. Investigation found a sinonasal malignancy and pathology confirmed this to be a primary germ cell tumour. The patient was managed with chemotherapy, surgery and consolidation radiotherapy and has remained well to date. This case report outlines an unusual presentation and diagnostic challenge for the primary care physician, ear, nose and throat surgeon, pathologist and oncologist with review of the surrounding literature.


Assuntos
Neoplasias Embrionárias de Células Germinativas/complicações , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Nasais/complicações , Neoplasias Nasais/terapia , Celulite Orbitária/etiologia , Sinusite/etiologia , Adulto , Terapia Combinada , Diagnóstico Diferencial , Humanos , Masculino , Doenças Raras
17.
Eur J Cancer ; 127: 139-149, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32007714

RESUMO

BACKGROUND: Up to 50% of men with poor prognosis, non-seminoma germ cell tumours (GCTs) die with standard BEP (bleomycin, etoposide and cisplatin) chemotherapy. An intensive regimen, CBOP/BEP (carboplatin, bleomycin, vincristine and cisplatin/BEP), met response targets in a randomised, phase II trial (74% complete response or partial response marker negative, 90% confidence interval (CI) 61%-85%). AIM: To assess long-term outcomes and late toxicity associated with CBOP/BEP. METHODS: Patients with poor prognosis extracranial GCT were randomised to 4xBEP or CBOP/BEP (2xCBOP, 2xBO, 3xBEP with 15,000iu of bleomycin). Low-dose, stabilising chemotherapy before entry was permitted. Response rates (primary outcome) were reported previously. Here, we report secondary outcomes: progression-free survival (PFS), overall survival (OS) and late toxicity. Prognostic factors and the impact of marker decline are assessed in exploratory analysis. RESULTS: Eighty-nine patients (43 CBOP/BEP) were randomised. After median 63 months follow-up, 3-year PFS is 55.7% (95% CI: 39.7%, 69.0%) for CBOP/BEP and 38.7% (95% CI: 24.7%, 52.4%) for BEP (hazard ratio [HR]: 0.59 (0.33, 1.06), p = 0.079). Three-year OS is 65.0% (48.8%, 77.2%) and 58.5% (43.0%, 71.2%), respectively (HR: 0.79 (0.41, 1.52), p = 0.49). Twelve-month toxicity was affected by subsequent treatments, with no clear differences between arms. Stabilising chemotherapy was associated with poorer PFS (HR: 2.09 (1.14, 3.81), p = 0.017), whereas unfavourable marker decline, in 60 (70%) patients, was not. CONCLUSION: Although not powered for PFS, results for CBOP/BEP are promising. Impact on OS was less clear (and will be affected by subsequent therapy). Further study in an international phase III trial is warranted. TRIAL REGISTRATION: ISRCTN 53643604.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Adolescente , Adulto , Bleomicina/administração & dosagem , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Prognóstico , Taxa de Sobrevida , Vincristina/administração & dosagem , Adulto Jovem
18.
Eur Urol ; 77(3): 344-351, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31901440

RESUMO

BACKGROUND: Standard management in the UK for high-risk stage 1 nonseminoma germ cell tumours of the testis (NSGCTT) is two cycles of adjuvant bleomycin, etoposide (360 mg/m2), and cisplatin (BE360P) chemotherapy, or surveillance. OBJECTIVE: To test whether one cycle of BE500P achieves similar recurrence rates to two cycles of BE360P. DESIGN, SETTING, AND PARTICIPANTS: A total of 246 patients with vascular invasion-positive stage 1 NSGCTT or combined seminoma + NSGCTT were centrally registered in a single-arm prospective study. INTERVENTION: One cycle comprising bleomycin 30000 IU on days 1, 8, and 15, etoposide 165 mg/m2 on days 1-3, and cisplatin 50 mg/m2 on days 1-2, plus antibacterial and granulocyte colony stimulating factor prophylaxis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was 2-yr malignant recurrence (MR); the aim was to exclude a rate of ≥5%. Participants had regular imaging and tumour marker (TM) assessment for 5 yr. RESULTS AND LIMITATIONS: The median follow-up was 49 mo (interquartile range 37-60). Ten patients with rising TMs at baseline were excluded. Four patients had MR at 6, 7, 13, and 27 mo; all received second-line chemotherapy and surgery and three remained recurrence-free at 5 yr. The 2-yr MR rate was 1.3% (95% confidence interval 0.3-3.7%). Three patients developed nonmalignant recurrences with localised teratoma differentiated, rendered disease-free after surgery. Grade 3-4 febrile neutropenia occurred in 6.8% of participants. CONCLUSIONS: BE500P is safe and the 2-yr MR rate is consistent with that seen following two BE360P cycles. The 111 study is the largest prospective trial investigating one cycle of adjuvant BE500P in high-risk stage 1 NSGCTT. Adoption of one cycle of BE500P as standard would reduce overall exposure to chemotherapy in this young population. PATIENT SUMMARY: Removing the testicle fails to cure many patients with high-risk primary testicular cancer since undetectable cancers are often present elsewhere. A standard additional treatment in Europe is two cycles of chemotherapy to eradicate these. This trial shows one cycle has few adverse effects and comparable outcomes to those seen with two cycles.


Assuntos
Antineoplásicos/administração & dosagem , Bleomicina/administração & dosagem , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Primárias Múltiplas/tratamento farmacológico , Seminoma/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adulto , Quimioterapia Adjuvante , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Primárias Múltiplas/patologia , Estudos Prospectivos , Medição de Risco , Seminoma/epidemiologia , Seminoma/patologia , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/patologia , Adulto Jovem
20.
J Clin Oncol ; 38(12): 1322-1331, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-31877087

RESUMO

PURPOSE: Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment. PATIENTS AND METHODS: Data from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses. RESULTS: Median time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year; P = .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last follow-up, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes. CONCLUSION: Outcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (< 2 years), and late viable NS relapse (> 2 years).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/cirurgia , Orquiectomia , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Resultado do Tratamento
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