Review of current best practice and priorities for research in radiation oncology for elderly patients with cancer: the International Society of Geriatric Oncology (SIOG) task force.

Radiotherapy (RT) is a key component of the management of older cancer patients. Level I evidence in older patients is limited. The International Society of Geriatric Oncology (SIOG) established a task force to make recommendations for curative RT in older patients and to identify future research priorities. Evidence-based guidelines are provided for breast, lung, endometrial, prostate, rectal, pancreatic, oesophageal, head and neck, central nervous system malignancies and lymphomas. Patient selection should include comorbidity and geriatric evaluation. Advances in radiation planning and delivery improve target coverage, reduce toxicity and widen eligibility for treatment. Shorter courses of hypofractionated whole breast RT are safe and effective. Conformal RT and involved-field techniques without elective nodal irradiation have improved outcomes in non-small-cell lung cancer (NSCLC) without increasing toxicity. Where comorbidities preclude surgery, stereotactic body radiotherapy (SBRT) is an option for early-stage NSCLC and pancreatic cancer. Modern involved-field RT for lymphoma based on pre-treatment positron emission tomography data has reduced toxicity. Significant comorbidity is a relative contraindication to aggressive treatment in low-risk prostate cancer (PC). For intermediate-risk disease, 4-6 months of hormones are combined with external beam radiotherapy (EBRT). For high-risk PC, combined modality therapy (CMT) is advised. For high-intermediate risk, endometrial cancer vaginal brachytherapy is recommended. Short-course EBRT is an alternative to CMT in older patients with rectal cancer without significant comorbidities. Endorectal RT may be an option for early disease. For primary brain tumours, shorter courses of postoperative RT following maximal debulking provide equivalent survival to longer schedules. MGMT methylation status may help select older patients for temozolomide alone. Stereotactic RT provides an alternative to whole-brain RT in patients with limited brain metastases. Intensity-modulated radiation therapy provides an excellent technique to reduce dose to the carotids in head and neck cancer and improves locoregional control in oesophageal cancer. Best practice and research priorities are summarised.

Radiation dermatitis: implicated factors, clinical aspects, possible prevention, and medical care.

The increasing incidence of cancer is due to many factors. Among them quite significant is considered the rising proportion of older people in the population and the modern methods of early diagnosis. Radiotherapy (RT), along with surgery and chemotherapy, is a major therapeutic modality in the management of cancer. In the context of current treatment methods and practice, approximately half of the patients with cancer will receive RT at some stage of their illness. RT can lead to cure some kinds of cancer but it can also be delivered for palliation. Unfortunately, skin damage is a complication affecting by and large all patients receiving external beam RT. In order to minimize the risk of this damage it would be helpful to know the complex underlying molecular mechanisms and evaluate the related clinical symptoms, not only for medical but also for psychological reasons related to the patient. The purpose of this article was to review the current approaches to this particular clinical condition, in order to realize an effective patient-oriented clinical practice and keep this radiation-induced complication as low as possible.

Pegulated liposomal doxorubicin and cisplatin given concurrently with conventional radiotherapy: a phase I dose-escalation trial for patients with squamous cell carcinoma of head and neck and lung.

This is a phase I study of concurrent chemoradiation with pegulated liposomal doxorubicin (PLDH) and cisplatin for patients with squamous non-small cell lung cancer (NSCLC) and head and neck carcinoma (SCCHN). Nine patients with NSCLC and 9 with SCCHN were recruited in two phase I dose-escalation trials. The starting dose of PLDH was 7 mg/m2 once a week and was increased by 5 mg/m2 dose increments for every 3 patients. The standard dose of cisplatin was 20 mg/m2 once a week for 6.5-7 weeks of conventional external irradiation. The total tumor dose was 64 and 70 Gy for NSCLC and SCCHN patients respectively. The maximum tolerated dose of PLDH was 12 mg/m2 for the two cohorts of patients. Grade 3 mucositis was the dose limiting toxicity for NSCLC and SCCHN patients, at the 17 mg/m2 dose level. Three chemoradiation delays of 7 days were confirmed. The median time of follow-up was 17.9 months (range 3-36 months). Four patients died due to local-regional failure combined with distant metastases (3 patients) and pericardial effusion (1 patient). In total, there were 6/18 (33%) CRs (95% confidence interval, 11-55%), and 10/18 (55%), PRs (95% confidence interval, 32-78%). The recommended phase II PLDH dose combined to cisplatin and external irradiation is 12 mg/m2/week. The incorporation of PLDH in concomitant chemoradiation regimens for future treatment of squamous cell carcinoma of the lung and head and neck is warranted.

Adrenomedullin inhibits the contraction of cultured rat testicular peritubular myoid cells induced by endothelin-1.

The present study documents that adrenomedullin (AM), a vasoactive peptide originally identified in pheochromocytoma tissue and present in the testis, in vitro affects the function of testicular peritubular myoid cells (TPMC), a contractile cell type located in the seminiferous tubule wall. AM stimulated cAMP production by cultured TPMC taken from 16-day-old rats, and this effect was completely inhibited by the AM antagonist AM-(22-52) and partially by the CGRP (calcitonin gene-related peptide) antagonist CGRP-(8-37). Studies on TPMC contractile activity documented that AM inhibits TPMC contraction induced by endothelin-1 (ET-1) and that its effect is antagonized by AM-(22-52). Neutralizing AM produced by TPMC with the addition of anti-AM antibody induced a significant increase of ET-1-induced contraction. When exposed to the protein kinase A inhibitor H-89, AM inhibitory activity on ET-1-induced TPMC contraction was suppressed, whereas the nitric oxide synthase inhibitor N:(G)-nitro-L-arginine methyl esther did not modify AM activity. In conclusion, our study indicates that AM stimulates cAMP production and inhibits the contraction induced by ET-1 in TPMC in vitro, and that AM produced by TPMC has an autocrine effect. We propose that AM may have a role in the control of seminiferous tubule contraction.

Testicular peritubular myoid cells are a target for adrenomedullin.

Adrenomedullin (AM) is a recently cloned vasorelaxing peptide that belongs to the calcitonin gene-related peptide family. AM inhibits the contraction of several types of smooth muscle cells and is present in the testis as well as in many other organs. The authors investigated whether testicular peritubular myoid cells (PMC) possess specific receptors for AM. Binding of AM to PMC was saturable in a time-dependent manner and 125I-AM binding was effectively displaced by cold AM. The study documents that testicular peritubular myoid cells are a target for adrenomedullin and suggests a role for this peptide in the paracrine regulation of the testis.

[Adrenal adenoma and myelolipoma in an elderly patient with Conn's syndrome]. / Adenoma surrenalico e mielolipoma in paziente anziano con sindrome di Conn.

Adrenal myelolipoma is an uncommon benign tumor usually discovered by chance in patients with hypertension, obesity, atherosclerosis, cancer or endocrine disorders. The association with adrenal endocrine dysfunctions appears to be the most frequent. Myelolipoma has been found in patients affected by Cushing's syndrome, hyperaldosteronism, Addison's disease, virilization. We report herein a case of association, based on clinical and radiological signs, between myelolipoma and adrenal adenoma in a patient with Conn's disease. The myelolipoma was localized in the opposite adrenal gland to that of adenoma, at difference with the other cases described.