Outcomes of Proton Therapy for Patients With Functional Pituitary Adenomas

Wattson, Daniel A.; Tanguturi, Shyam; Spiegel, Daphna Y.; Niemierko, Andrzej; Biller, Beverly M. K.; Nachtigall, Lisa B.; Bussière, Marc R.; Swearingen, Brooke; Chapman, Paul H.; Loeffler, Jay S.; Shih, Helen A.

doi:10.1016/j.ijrobp.2014.06.068

Cited by 100 publications

(55 citation statements)

References 31 publications

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“…The optimal dose is 20-25 Gy for SRS and 45-50.4 Gy given over 5 weeks for radiation therapy. 85,98 Generally, the incidence of remission in CD seems to be similar between the various forms of radiosurgery (43%-58%) and fractionated therapies (46%-84%; Table 3), 13,30,85,94,98,108,109 but the pace of the therapeutic response may be faster with SRS. The major risk of SRS or fractionated irradiation therapy is loss of pituitary function, which is presumably the net effect of surgery and radiation.…”

Section: Radiation Therapymentioning

confidence: 97%

Cushing's disease: pathobiology, diagnosis, and management

Lonser

Nieman

Oldfield

2017

JNS

151

114

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Cushing's syndrome (CS) is caused by prolonged supraphysiological levels of circulating cortisol. Cushing's disease (CD) is the most common etiology (70%-80% of CS cases) of endogenous CS. It is caused by a pituitary adenoma that secretes adrenocorticotropic hormone (ACTH), which stimulates secretion of cortisol by the adrenal glands. If not effectively treated, CD is associated with hypertension, diabetes, obesity, osteoporosis, vascular disease, and shortened life span. Successful resection of a CD-associated ACTH-secreting pituitary adenoma results in immediate biochemical remission and preservation of pituitary function. Early identification of CD by clinical findings, endocrinological evaluation, and imaging studies is critical for diagnosis and effective surgical management. endocrinological and Clinical Features endocrinological Features Normal PhysiologyInsight into the normal and pathophysiological mechanisms of control of the hypothalamic-anterior pituitaryadrenal axis is critical to understanding the pathologic, diagnostic, and therapeutic features of CD (Fig. 1). 52 Under normal physiological conditions (circadian rhythm, where cortisol levels peak in early morning and nadir late at night), systemic inflammation (cytokine), or stress (physiological or psychological), corticotropin-releasing hormone (CRH; a 41-amino acid peptide) is released from the paraventricular hypothalamic nucleus via the median eminence. From the median eminence, CRH is transported in the hypophyseal portal venous system to the pituitary gland, where it binds to the CRH receptor-1 (CRH-R1) on pituitary corticotroph cells. CRH binding to CRH-R1 receptors activates adenylate cyclase and stimulates proopiomelanocortin (POMC) gene expression in the corticotroph cells.17,66 Proopiomelanocortin preprohormone is processed into ACTH (a 39-amino acid peptide) and b-lipotropin (a 93-amino acid peptide). Products of b-lipotropin include b-endorphin and a-lipotropin. ACTH is secreted into the systemic circulation and binds to receptors in the adrenal cortex, where it stimulates production and secretion of glucocorticoids, including cortisol. 83 Under normal conditions, circulating cortisol provides physiological control of this endocrine axis by its negative feedback inhibition on hypothalamic CRH and pituitary ACTH secretion. Cushing's disease (CD) is the result of excess secretion of adrenocorticotropic hormone (ACTH) by a benign monoclonal pituitary adenoma. The excessive secretion of ACTH stimulates secretion of cortisol by the adrenal glands, resulting in supraphysiological levels of circulating cortisol. The pathophysiological levels of cortisol are associated with hypertension, diabetes, obesity, and early death. Successful resection of the CD-associated ACTH-secreting pituitary adenoma is the treatment of choice and results in immediate biochemical remission with preservation of pituitary function. Accurate and early identification of CD is critical for effective surgical management and optimal prognosis. The authors review the cu...

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Section: Radiation Therapymentioning

confidence: 97%

Cushing's disease: pathobiology, diagnosis, and management

Lonser

Nieman

Oldfield

2017

JNS

151

114

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“…Several series have suggested that proton beam may be a step forward in this regard [72][73][74][75] . Other benign tumors of the skull base have been treated successfully with protons such as acoustic neuroma or pituitary adenoma [76][77][78] .…”

Section: Brain Tumorsmentioning

confidence: 99%

The actual Interest in Radiotherapy for the Utilization of Proton Beam, Highlighting Physics Basis, Technology and Common Clinical Indications

Amichetti

2016

Journal of Tumor

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. Since that years, commercial entities began to build cyclotrons and synchrotrons for clinical purposes. Over the last 10 years, PBT has gathered more interest in the scientific community and more media and patient attention and is now flourishing in the US and abroad. As of December, 2015, 57 proton therapy centers are in operation worldwide, others are under construction and many more in a planning phase [3] . Most patients who have been treated with heavy-particle therapy were treated with protons: PTCOG (Particle Therapy Co-Operative Group) reports that between 1954 and 2014, 137 000 patients globally received part or all of their radiation therapy with particles, and in particular 86% of them with protons [4] . The generation of these particles and the building of dedicated centers, however, requires large investments and operational costs and big infrastructure. Only relatively few studies have demonstrated the effectiveness of proton therapy and the effects are surrounded with uncertainty [5] being the cost-effectiveness still the core of the controversy around the use of PBT. ABSTRACTManaging expensive technology is a debated issue in modern radiation oncology. Proton beam therapy (PBT) represents, considering its cost and its foreseen benefits, a typical case of discussion waiting for more robust results demonstrating the presumable clinical gains against the available radiation therapy (XRT) treatment alternatives based on the use of photons. The treatment with particles utilizes many different beams (neutrons, protons, pions, or helium, neon, argon, and carbon ions) that represent a distinct entity respect conventional XRT which uses photons. PBT is the most common form of heavy-particle radiation therapy used so far; it is not a new invention, being its clinical use proposed in a seminal article by R. Wilson in 1946 [1] and the first patients treated in 1954 at the Lawrence Berkeley National Laboratory in California [2] . Since cyclotron or synchrotron, used to accelerate protons to therapeutic energies, were used primarily for research in particle or nuclear physics, the initial clinical activity in proton therapy was carried out in research facilities and the use of protons in clinical practice has grown slowly for several years in non-clinical setting. More than fifty years later, after a long period of seminal work in a limited number of Institutions, PBT has gained public attention in recent years because of the rapidly increasing number of centers around the world, regardless of their high cost. Hospital-based proton beam facilities have been in operation since 1990 after the opening of the first dedicated clinical center at Loma Linda Medical

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“…As três modalidades principais de radioterapia indicadas para o tratamento da síndrome de Nelson são: radioterapia estereotática fracionada ou radiocirurgiaestereotática com acelerador linear -através Raios X de alta energia obtém o controle da doença em cerca de 60% dos pacientes 25 ; terapia de feixe de prótons -utiliza feixe de partículas, com taxa de controle de 63% 45 e radiocirurgiaGammaKnife com taxas de controle entre 82 e 91% 47 .…”

Section: Radioterapiaunclassified

Revisitando a síndrome de Nelson

Pallone¹,

Schwambach²,

Manosso³

et al. 2016

Rev. Med. UFPR

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RESUMOA síndrome de Nelson é caracterizada pela tríade de hiperpigmentação cutânea, níveis elevados de ACTH e expansão do tumor hipofisário após adrenalectomia bilateral como terapia para Doença de Cushing. Apresenta taxas de incidência que variam de 0 a 47% e tem como principais fatores preditivos para o seu surgimento os níveis de ACTH plasmático no primeiro ano após a adrenalectomia, duração da doença de Cushing até a retirada das adrenais e tratamento prévio com radioterapia para o tratamento da doença de Cushing. Os critérios diagnósticos para essa doença consistem na adrenalectomia bilateral em pacientes com doença de Cushing associada à elevação nos níveis de ACTH (acima de 500 ng/L ou aumento de pelo menos 30% do valor em três amostras consecutivas) e/ou imagem hipofisária com lesão tumoral. O tratamento de primeira linha é a ressecção da lesão através da cirurgia transesfenoidal, porém radioterapia e tratamento farmacológico com cabergolina, pasireotide ou temozolamida podem ser necessários em alguns casos.Descritores: Síndrome de Nelson, doença de cushing, ACTH, adenoma hipofisário, adrenalectomia bilateral. ABSTRACTThe Nelson syndrome is characterized by the triad of cutaneous hyperpigmentation, high levels of ACTH and increase of a pituitary tumor after bilateral adrenalectomy for treatment of Cushing's disease. It presents an incidence rate from 0-47%, and the main predictive factors for its emergence is ACTH plasma levels in the first year after adrenalectomy, duration of Cushing's disease before removal of adrenal glands and previous treatment with radiotherapy. The diagnostic criteria for Nelson syndrome is adrenalectomy in patients with Cushing's disease associated with elevated levels of ACTH (higher than 500 ng/L or an increase of at least 30% in three consecutive samples) and/or pituitary imaging with tumor lesion. Resection of tumor by transsphenoidal surgery is the first-line treatment, but radiotherapy and pharmacological therapy with cabergoline, pasireotide or temozolomide may be used in some cases.

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Outcomes of Proton Therapy for Patients With Functional Pituitary Adenomas

Cited by 100 publications

References 31 publications

Cushing's disease: pathobiology, diagnosis, and management

Cushing's disease: pathobiology, diagnosis, and management

The actual Interest in Radiotherapy for the Utilization of Proton Beam, Highlighting Physics Basis, Technology and Common Clinical Indications

Revisitando a síndrome de Nelson

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