Radiotherapy for prevention or management of gynecomastia recurrence: Future role for general gynecomastia patients in plastic surgery given current role in management of high-risk prostate cancer patients on anti-androgenic therapy.

PURPOSE: Several technologies and innovative approaches continue to emerge for the optimal management of gynecomastia by plastic surgeons; the present study investigates the role of radiation therapy in this context. METHODS: A systematic review was performed to evaluate the utility of radiotherapy for the prevention and treatment of gynecomastia incidence or recurrence by plastic surgeons. RESULTS: Fifteen articles met the inclusion criteria for review. The mean incidence of gynecomastia was 70% in the high-risk population examined representing prostate cancer patients on estrogen or anti-androgen therapy. Radiotherapy was shown to significantly reduce the incidence to a median of 23%, with all six randomized control studies assessed demonstrating a statistically significant decrease in incidence following radiotherapy prophylaxis. Doses examined ranged from 8 to 16 Gy, delivered between 1 and 11 fractions. Complications following radiotherapy were minor and self-limiting in all cases, restricted to minor skin reactions, and associated with larger radiotherapy doses delivered in fewer fractions. The median complication rate was 12.4% with no major complications, such as neoplastic, pulmonary, or adverse cardiac outcomes. While the efficacy of radiation therapy as a treatment modality for gynecomastia was also established, it was shown to be less effective than other available options. CONCLUSIONS: Low-dose radiotherapy to the male breast might be a safe and effective strategy to prevent gynecomastia incidence or recurrence in high-risk patients; further studies are indicated within the common gynecomastia population managed by plastic surgeons to assess the clinical and economical utility of this intervention before a recommendation for its ubiquitous adoption in plastic surgery can be made to continue improving outcomes for high-risk gynecomastia patients.

Treatment strategies to prevent and reduce gynecomastia and/or breast pain caused by antiandrogen therapy for prostate cancer : Statement from the DEGRO working group prostate cancer.

AIM: To provide an overview on the available treatments to prevent and reduce gynecomastia and/or breast pain caused by antiandrogen therapy for prostate cancer. METHODS: The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published and assessed the validity of the information on efficacy and treatment-related toxicity. RESULTS: Eight randomized controlled trials and one meta-analysis were identified. Two randomized trials demonstrated that prophylactic radiation therapy (RT) using 1â€¯× 10 Gy or 2â€¯× 6 Gy significantly reduced the rate of gynecomastia but not breast pain, as compared to observation. A randomized dose-finding trial identified the daily dose of 20 mg tamoxifen (TMX) as the most effective prophylactic dose and another randomized trial described that daily TMX use was superior to weekly use. Another randomized trial showed that prophylactic daily TMX is more effective than TMX given at the onset of gynecomastia. Two other randomized trials described that TMX was clearly superior to anastrozole in reducing the risk for gynecomastia and/or breast pain. One comparative randomized trial between prophylactic RT using 1â€¯× 12 Gy and TMX concluded that prophylactic TMX is more effective compared to prophylactic RT and furthermore that TMX appears to be more effective to treat gynecomastia and/or breast pain when symptoms are already present. A meta-analysis confirmed that both prophylactic RT and TMX can reduce the risk of gynecomastia and/or breast pain with TMX being more effective; however, the rate of side effects after TMX including dizziness and hot flushes might be higher than after RT and must be taken into account. Less is known regarding the comparative effectiveness of different radiation fractionation schedules and more modern RT techniques. CONCLUSIONS: Prophylactic RT as well as daily TMX can significantly reduce the incidence of gynecomastia and/or breast pain. TMX appears to be an effective alternative to RT also as a therapeutic treatment in the presence of gynecomastia but its side effects and off-label use must be considered.

[A survey of Belgian practice for non-malignant diseases]. / Une enquête de l'utilisation en Belgique de la radiothérapie pour des affections bénignes, non-tumorales.

Two prior surveys were carried out in 1995 and 1999 to evaluate the use of radiotherapy in the treatment of non-malignant disease. In 2016, the same questionnaire was used and sent to the 24 centers of the country: 22 responded. A major decrease was observed in the number of patients treated: 360 in 2016 in contrast to 954 in 1999 and 1113 in 1995. The most frequent indications remain the prevention of heterotopic bone formation, keloids or gynecomastia. A new indication was observed: trigeminal nevralgia treated with radiosurgery. Two frequent indications in the past disappeared: the prevention of coronary restenosis and the macular degeneration. A great agreement was observed regarding the possible indications for radiotherapy but also to avoid it for inflammatory pathologies.

Radiation Therapy for Benign Disease: Arteriovenous Malformations, Desmoid Tumor, Dupuytren Contracture, Graves Ophthalmopathy, Gynecomastia, Heterotopic Ossification, Histiocytosis.

Although the use of ionizing radiation in malignant conditions has been well established, its application in benign conditions has not been fully accepted and has been inadequately recognized by health care providers outside of radiation therapy. Most frequently, radiation therapy in these benign conditions is used along with other treatment modalities, such as surgery, in instances where the condition causes significant disability or could even lead to death. Radiation therapy can be helpful for inflammatory/proliferative disorders. This article discusses the current use of radiation therapy in some of the more common benign conditions.

Radiotherapy for prevention and therapy of gynecomastia due to antiandrogen treatment in prostate cancer patients: a patterns-of-care study.

BACKGROUND: Gynecomastia is a frequent side effect of antiandrogen therapy for prostate cancer and may compromise quality of life. Although it has been successfully treated with radiotherapy (RT) for decades, the priority of RT as a preferred treatment option has recently been disputed as tamoxifen was also demonstrated to be effective. The aim of the present paper is to provide an overview of indications, frequency, and technique of RT in daily practice in Germany, Switzerland, and Austria. PATIENTS AND METHODS: On behalf of the DEGRO-AG GCG-BD (German Cooperative Group on Radiotherapy of Benign Diseases) a standardized questionnaire was sent to 294 RT institutions. The questionnaires inquired about patient numbers, indications, RT technique, dose, and - if available - treatment results. Moreover, the participants were asked whether they were interested in participating in a prospective study. RESULTS: From a total of 294 institutions, 146 replies were received, of which 141 offered RT for gynecomastia. Seven of those reported prophylactic RT only, whereas 129 perform both preventive and symptomatic RT. In 110 of 137 departments, a maximum of 20 patients were treated per year. Electron beams (76%) were used most often, while 24% of patients received photon beams or orthovolt x-rays. Total doses were up to 20 Gy for prophylactic and up to 40 Gy for therapeutic RT. Results were reported by 19 departments: prevention of gynecomastia was observed in 60-100% of patients. Only 13 institutions observed side effects. CONCLUSION: Prophylactic and symptomatic RT is widely used in the German-speaking countries, but patient numbers are small. The clinical results indicate that RT is a highly effective and well-tolerated treatment.

Treatment of benign diseases with megavoltage X-ray beams: is there a risk for gonadal damage?

AIMS: To measure the testicular and ovarian doses and to assess the risk for gonadal damage to patients treated with megavoltage X-ray beams for benign diseases. MATERIALS AND METHODS: Radiation therapy of benign diseases was simulated on an anthropomorphic phantom with a 6MV photon beam. The gonadal dose was calculated during the irradiation of heterotopic ossification, liver and vertebra haemangiomas, bone cysts, Graves' ophthalmopathy and gynaecomastia. Dose measurements were carried out using thermoluminescent dosimeters. For the radiotherapy of heterotopic ossification, the effect of using lead blocks to spare lymphatic drainage on the gonadal dose was determined. RESULTS: The ovarian and testicular total doses were found to be 2.00-680 and 2.0-39.0 mGy, respectively, depending on the gonadal location in respect to the treatment volume. The introduction of blocks into the primary beam resulted in an increase in gonadal dose up to a factor of 1.7. The radiation-induced risk of hereditary disorders in future generations was (1.0-40.8) x 10(-4) and (1.0-23.4) x 10(-4) for women and men, respectively. CONCLUSIONS: Radiation therapy of benign diseases always resulted in gonadal doses below 1 Gy and therefore there was no risk for permanent gonadal failure. The excess risk of radiation-induced hereditary disorders in offspring was low in comparison with the natural frequency of these effects. However, there was a considerable excess in risk after irradiation in the hip bone.

The role of radiation therapy in benign diseases.

Although adequate prospective data are lacking, radiation therapy seems to be effective for many benign diseases and remains one of the treatment modalities in the armamentarium of medical professionals. Just as medication has potential adverse effects, and surgery has attendant morbidity, irradiation sometimes can be associated with acute and chronic sequelae. In selecting the mode of treatment, most radiation oncologists consider the particular problem to be addressed and the goal of therapy in the individual patient. It is the careful and judicial use of any therapy that identifies the professional. With an understanding of the current clinical data, treatment techniques, cost, and potential detriment, the goal is to provide long-term control of the disease while minimizing unnecessary treatment and potential risks of side effects. The art lies in balancing benefits against risks.

The current management of gynecomastia: an update.

Gynecomastia is a common condition characterized by a benign proliferation of the glandular component of the male breast. It is thought to be due to an increase in the ratio of estrogen to androgen activity. The present article reviews the pathogenesis, clinical features, and contemporary treatment of gynecomastia.

Management of gynaecomastia in patients with prostate cancer: a systematic review.

Patients with prostate cancer are increasingly being offered treatment with non-steroidal antiandrogen monotherapy, which offers potential quality-of-life benefits compared with other treatment. Non-steroidal antiandrogens directly antagonise androgen action in breast tissue, and indirectly increase the oestrogen concentration. Thus, the most troublesome side-effects of monotherapy with these drugs are gynaecomastia and breast pain. Patients younger than 60 years of age, who might not have symptoms of prostate cancer, are probably more concerned about their body image and the development of enlarged breasts than are those older than 60 years. Clinicians who seek a treatment for prostate cancer need information on simple and well-tolerated options for the management of gynaecomastia and breast pain. In this review, management options for gynaecomastia caused by hormonal manipulation in patients with prostate cancer are discussed.

Efficacy of tamoxifen and radiotherapy for prevention and treatment of gynaecomastia and breast pain caused by bicalutamide in prostate cancer: a randomised controlled trial.

BACKGROUND: Gynaecomastia and breast pain are frequent adverse events with bicalutamide monotherapy, and might cause some patients to withdraw from treatment. We aimed to compare tamoxifen with radiotherapy for prevention and treatment of gynaecomastia, breast pain, or both during bicalutamide monotherapy for prostate cancer. METHODS: 51 patients were randomly assigned to 150 mg bicalutamide per day, 50 patients to 150 mg bicalutamide per day and to 10 mg tamoxifen per day for 24 weeks, and 50 patients to 150 mg bicalutamide per day and radiotherapy (one 12-Gy fraction on the day of starting bicalutamide). 35 of the 51 patients allocated bicalutamide alone developed gynaecomastia or breast pain and were subsequently randomly allocated to tamoxifen (n=17) or radiotherapy (n=18) soon after symptoms started (median 180 days, range 160-195). Gynaecomastia and breast pain were assessed once a month. Severity of gynaecomastia was scored on the basis of the largest diameter. Breast pain was scored as none, mild, moderate, or severe. The primary outcome was frequency of gynaecomastia or breast pain; secondary outcomes were safety and tolerability, relapse-free survival, as assessed by concentration of prostate specific antigen, and quality of life. Analyses were by intention to treat. RESULTS: 35 of 51 patients assigned bicalutamide alone developed gynaecomastia, compared with four of 50 assigned bicalutamide and tamoxifen (odds ratio [OR] 0.1 [95% CI 0.08-0.12], p=0.0009), and with 17 of 50 assigned bicalutamide and radiotherapy (0.51 [0.47-0.54], p=0.008). Breast pain was seen in 29 of 51 patients allocated bicalutamide alone, compared with three allocated bicalutamide and tamoxifen (0.1 [0.07-0.11], p=0.009), and with 15 allocated bicalutamide and radiotherapy (0.43 [0.40-0.45], p=0.02) In 35 patients assigned bicalutamide alone who subsequently developed gynaecomastia, breast pain, or both, tamoxifen significantly reduced the frequency of gynaecomastia (0.2 [0.18-0.22], p=0.02). INTERPRETATION: Antioestrogen treatment with tamoxifen could help patients with prostate cancer to tolerate the hypergonadotropic effects of bicalutamide monotherapy.

Efficacy and tolerability of radiotherapy as treatment for bicalutamide-induced gynaecomastia and breast pain in prostate cancer.

OBJECTIVE: To assess the efficacy and tolerability of localised radiotherapy for the treatment of bicalutamide ('Casodex''Casodex' is a trademark of the AstraZeneca group of companies.)-induced gynaecomastia and/or breast pain. METHODS: This open-label, non-comparative, multicentre study included 51 patients receiving bicalutamide 150 mg for the treatment of non-metastatic prostate cancer (T1b-T4, Nx, M0). Patients who developed symptomatic gynaecomastia and/or breast pain received two 6-Gy fractions of external-beam radiation to the breasts and were then assessed at two 3-monthly follow-up visits. RESULTS: 37/51 (72.5%) patients experienced gynaecomastia and 41/51 (80.4%) experienced breast pain, typically within the first 6 months. Twenty seven and 38 patients, respectively, went on to receive breast irradiation. Following radiotherapy, gynaecomastia improved or resolved in 7/27 (25.9%) and 2/27 (7.4%) cases, respectively, and breast pain improved or resolved in 12/38 (31.6%) and 3/38 (7.9%) cases, respectively. No change was observed in 7 patients (25.9%) with gynaecomastia and 12 patients (31.6%) with breast pain, while 9 patients (33.3%) and 8 patients (21.1%), respectively, worsened. Radiotherapy-related adverse events, reported by 18/41 (43.9%) patients, were generally mild and short lived (median duration approximately 5 weeks). CONCLUSIONS: Therapeutic radiotherapy, using two fractions of 6 Gy external-beam radiation to the male breast, improves the intensity of bicalutamide-induced gynaecomastia and/or breast pain in approximately one-third of patients. Adverse events were often mild and short lived.

Unilateral breast enlargement as a presenting feature of small cell carcinoma of the lung.

Breast enlargement associated with carcinoma of the lung is most commonly a paraneoplastic manifestation of non-small cell carcinoma. Hormonally mediated proliferation of the glandular component of the breast leads to unilateral or bilateral enlargement. This report describes a patient with small cell carcinoma of the lung who presented with unilateral breast enlargement related to superior vena cava obstruction.

Prophylactic breast irradiation with a single dose of electron beam radiotherapy (10 Gy) significantly reduces the incidence of bicalutamide-induced gynecomastia.

PURPOSE: To evaluate the efficacy and tolerability of prophylactic breast irradiation in reducing the incidence and severity of bicalutamide-induced gynecomastia and breast pain. METHODS AND MATERIALS: In all, 106 men with prostate cancer (T1b-T4/Nx/M0) and no current gynecomastia/breast pain were enrolled in this randomized, sham-controlled, double-blind, parallel-group multicenter trial. Patients received either a single dose of electron beam radiotherapy (10 Gy) or sham radiotherapy. Bicalutamide (Casodex) 150 mg/day was administered for 12 months from the day of radiotherapy. Every 3 months, patients underwent physical examination and questioning about gynecomastia and breast pain. RESULTS: The incidence of investigator-assessed gynecomastia was significantly lower with radiotherapy vs. sham radiotherapy (52% vs. 85%; odds ratio [OR], 0.13; 95% confidence interval [CI], 0.04, 0.38; p < 0.001); direct questioning showed similar results. Fewer radiotherapy patients had >/=5 cm gynecomastia (measured by calipers; 11.5% vs. 50.0% for sham radiotherapy), and fewer cases were moderate-to-severe in intensity (21% vs. 48%). Similar proportions of radiotherapy and sham radiotherapy patients experienced breast pain (83% vs. 91%; OR, 0.25; 95% CI, 0.05, 1.27; p = 0.221); patients receiving radiotherapy experienced some reduction in its severity (OR, 0.44; 95% CI, 0.20, 0.97; p = 0.0429). CONCLUSIONS: Prophylactic breast irradiation is an effective and well-tolerated strategy for prevention of bicalutamide-induced gynecomastia.

[Antiandrogen gynecomastia: an inescapable harm? Radiotherapy: a simple and efficient solution!]. / La gynécomastie sous anti-androgènes: un mal inéluctable? La radiothérapie: une solution simple et efficace!

Anti-androgen induced gynecomastia, resulting from a treatment induced imbalance between oestrogens and androgens, is a frequently encountered side effect in the hormonal treatment of patients with prostatic cancer. One might expect to face an increase in the overall incidence of this side effect in the next-coming years as randomized trials clearly point to the evidence of the therapeutic benefit of anti-androgenic treatment for this prostatic cancer. Gynecomastia is often accompanied by mastodynia and does hamper quality of life. Surgery should be considered for established irreversible gynecomastia characterized by hyalinization and extensive fibrosis. However, radiotherapy is the treatment of choice for gynecomastia at it's early stage, or could eventually be considered as a prophylactic treatment in high risk patients. It is a safe and extremely well tolerated treatment resulting in a high degree of therapeutic success with a demonstrated effect on quality of life as reported in randomized trials. To date no medical treatment is proven effective nor devoid from deleterious effects and licenced for this indication.

The safety and tolerability of low-dose irradiation for the management of gynaecomastia caused by antiandrogen monotherapy.

Gynaecomastia--a benign and often painful enlargement of the male breast--is a common side-effect of some therapies for prostate cancer, including non-steroidal antiandrogen monotherapy. Although gynaecomastia and breast pain are not harmful to the overall health of the patient, they can be serious enough to influence treatment decisions in the management of prostate cancer. Prophylactic low-dose irradiation can be effective in reducing the incidence and severity of both gynaecomastia and breast pain. In addition, irradiation may be effective in treating breast pain due to the development of gynaecomastia. Low-dose electron irradiation confers advantageous tissue dosing, is well tolerated, and has manageable side-effects, the most common of which is reversible skin erythema. Information on long-term safety after irradiation for gynaecomastia is limited at present, but trials are underway. Irradiation is likely to be an effective management option with an acceptable low risk of long-term complications for gynaecomastia associated with hormone therapy for prostate cancer.

Treatment of gynecomastia.

Gynecomastia is a common problem during puberty as well as later adulthood, and is caused by hormonal imbalance at the breast tissue level. Various medications and medical conditions can cause gynecomastia and when the drug is discontinued or medical condition cured, it will frequently resolve. Medical therapy can be tried for patients with persistent gynecomastia associated-tenderness or social embarrassment prior to contemplating surgical removal of the breast tissue.

[Radiotherapy of non-malignant diseases: principles and recommendations]. / Strahlenbehandlung von nicht-malignen Erkrankungen: Grundsätze und Empfehlungen.

The plenty options and high quality of radiation therapy for non-malignant disorders is not well known outside the field of radiology. It is necessary to transfer this information to cooperating general practitioners, surgeons, orthopedics and other specialists. To warrant quality assurance and quality control and to allow a uniform performance of radiotherapy of non-malignant conditions, general guidelines and recommendations according to the German Working Group of Scientific Medical Societies are useful. This paper summarizes the essential aspects of radiotherapy for non-malignant diseases: indication of, informed consent for, documentation and conduct of radiation therapy for non-malignant diseases using orthovoltage equipment and specific recommendations for follow up examinations. Radiotherapy concepts for non-malignant diseases are summarized.