Prevalence of Cardiovascular Disease and Osteoporosis During Androgen Deprivation Therapy Prescription Discordant to EAU Guidelines: Results From a Multicenter, Cross-sectional Analysis From the CHOsIng Treatment for Prostate canCEr (CHOICE) Study.

OBJECTIVE: To analyze the prevalence of cardiovascular disease (CVD) and osteoporosis in patients treated with androgen deprivation therapy (ADT) for prostate cancer (PCa) but not adherent to European Association of Urology (EAU) guidelines. MATERIALS AND METHODS: The CHOosIng Treatment for Prostate CanCEr (CHOICE) study was an Italian multicenter, cross-sectional study conducted from December 2010 to January 2012. A total of 1386 patients treated with ADT for PCa (first prescription or renewal of ADT) were selected. According to EAU guidelines, the cohort was categorized in discordant ADT (Group A) and concordant ADT (Group B). The prevalence of CVD and osteoporosis after ADT was recorded. RESULTS: The final cohort included 1075 patients. According to EAU guidelines adherence, 285 (26.51%) and 790 (73.49%) were considered discordant and concordant, respectively. The proportion of men with Charlson Comorbidity Index > 2 at baseline was statistically similar in Group A (81.8%) compared to Group B (80.8%) (P = .96). The number of complications reported at enrollment was as follows: cardiovascular in 351 (32.7%), endocrine in 166 (15.4%), sexual in 498 (46.3%), osteoporosis in 181 (16.8%), and gynecomastia in 274 (25.5%) subjects. At the multivariate logistic regression analysis adjusted for confounding factors, discordant ADT was associated with greater risk of cardiovascular complications (odds ratio: 2.07; P < .01) and osteoporosis (odds ratio: 1.75; P = .04). CONCLUSION: About one-third of patients with PCa received inappropriate ADT and showed a greater risk of CVD and osteoporosis. These results could be useful for setting better policy strategies to limit the inappropriateness of ADT prescription.

Patterns of prescription and adherence to European Association of Urology guidelines on androgen deprivation therapy in prostate cancer: an Italian multicentre cross-sectional analysis from the Choosing Treatment for Prostate Cancer (CHOICE) study.

OBJECTIVE: To evaluate both the patterns of prescription of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) and the adherence to European Association of Urology (EAU) guidelines for ADT prescription. METHODS: The Choosing Treatment for Prostate Cancer (CHOICE) study was an Italian multicentre cross-sectional study conducted between December 2010 and January 2012. A total of 1 386 patients, treated with ADT for PCa (first prescription or renewal of ADT), were selected. With regard to the EAU guidelines on ADT, the cohort was categorized into discordant ADT (Group A) and concordant ADT (Group B). RESULTS: The final cohort included 1 075 patients with a geographical distribution including North Italy (n = 627, 58.3%), Central Italy (n = 233, 21.7%) and South Italy (n = 215, 20.0%). In the category of patients treated with primary ADT, a total of 125 patients (56.3%) were classified as low risk according to D'Amico classification. With regard to the EAU guidelines, 285 (26.51%) and 790 patients (73.49%) were classified as discordant (Group A) and concordant (Group B), respectively. In Group A, patients were more likely to receive primary ADT (57.5%, 164/285 patients) than radical prostatectomy (RP; 30.9%, 88/285 patients), radiation therapy (RT; 6.7%, 19/285 patients) or RP + RT (17.7%, 14/285 patients; P < 0.01). Multivariate logistic regression analysis, adjusted for clinical and pathological variables, showed that patients from Central Italy (odds ratio [OR] 2.86; P < 0.05) and South Italy (OR 2.65; P < 0.05) were more likely to receive discordant ADT. CONCLUSION: EAU guideline adherence for ADT was low in Italy and was influenced by geographic area. Healthcare providers and urologists should consider these results in order to quantify the inadequate use of ADT and to set policy strategies to overcome this risk.

Treatment of irradiated expanders: protective lipofilling allows immediate prosthetic breast reconstruction in the setting of postoperative radiotherapy.

BACKGROUND: Immediate two-stage prosthetic breast reconstruction in the setting of postmastectomy radiotherapy (PMRT) currently is hardly achieved with the fast-track expander exchange proposed by Cordeiro and colleagues or the delayed-immediate breast reconstruction proposed by Kronowitz and Robb. Each of these techniques has important drawbacks and complications. To overcome these problems, the authors in 2011 described lipofilling on irradiated expanders in patients undergoing unplanned PMRT (Cagliari University Hospital [CUH] protocol) for early breast cancers with specific risk factors. The authors report their experience after expanding the use of such a protocol for any immediate expander/implant reconstruction in a patient undergoing PMRT. METHODS: The timing for advanced breast cancer involves immediate reconstruction with a tissue expander, complete tissue expansion, radiotherapy (RT) after neoadjuvant chemotherapy starting 2-3 months after mastectomy, one or two fresh fat-grafting sessions at least 6 weeks after RT, and an expander-implant exchange with anterior capsulectomy at least 3 months after the completion of fat grafting. The timing for early breast cancers with specific risk factors involves immediate reconstruction with a tissue expander, complete tissue expansion during postoperative chemotherapy, RT 6 months after mastectomy, one or two fat-grafting sessions 6 weeks after RT, and an expander-implant exchange with anterior capsulectomy at least 3 months after the completion of fat grafting. From 2008 to 2012, 16 patients undergoing total mastectomy and immediate expander-implant breast reconstruction with subsequent PMRT were treated according to the CUH protocol. RESULTS: The results have been extremely encouraging, with rates of ulceration and implant exposure in the radiotreated area dropping to 0 %. These results were retrospectively compared with those for a control group of 16 patients who underwent immediate implantation of an expander. In this latter group, the extrusion rate of the implant in the end was 31.25 %, and this was statistically significant (p < 0.03). The shape and symmetry also were significantly better in the lipofilled patients. CONCLUSION: Protective lipofilling on irradiated expanders appears to be a valid technique for avoiding ulceration and implant exposure after PMRT while allowing a complete expansion. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Planning hybrid intensity modulated radiation therapy for whole-breast irradiation.

PURPOSE: To test tangential and not-tangential hybrid intensity modulated radiation therapy (IMRT) for whole-breast irradiation. METHODS AND MATERIALS: Seventy-eight (36 right-, 42 left-) breast patients were randomly selected. Hybrid IMRT was performed by direct aperture optimization. A semiautomated method for planning hybrid IMRT was implemented using Pinnacle scripts. A plan optimization volume (POV), defined as the portion of the planning target volume covered by the open beams, was used as the target objective during inverse planning. Treatment goals were to prescribe a minimum dose of 47.5 Gy to greater than 90% of the POV and to minimize the POV and/or normal tissue receiving a dose greater than 107%. When treatment goals were not achieved by using a 4-field technique (2 conventional open plus 2 IMRT tangents), a 6-field technique was applied, adding 2 non tangential (anterior-oblique) IMRT beams. RESULTS: Using scripts, manual procedures were minimized (choice of optimal beam angle, setting monitor units for open tangentials, and POV definition). Treatment goals were achieved by using the 4-field technique in 61 of 78 (78%) patients. The 6-field technique was applied in the remaining 17 of 78 (22%) patients, allowing for significantly better achievement of goals, at the expense of an increase of low-dose (∼5 Gy) distribution in the contralateral tissue, heart, and lungs but with no significant increase of higher doses (∼20 Gy) in heart and lungs. The mean monitor unit contribution to IMRT beams was significantly greater (18.7% vs 9.9%) in the group of patients who required 6-field procedure. CONCLUSIONS: Because hybrid IMRT can be performed semiautomatically, it can be planned for a large number of patients with little impact on human or departmental resources, promoting it as the standard practice for whole-breast irradiation.

Prostate image-guided radiotherapy by megavolt cone-beam CT.

PURPOSE: To test megavolt cone-beam CT (MV-CBCT) in order to evaluate setup errors in prostate radiotherapy. PATIENTS AND METHODS: The setup of 9 patients was verified weekly by electronic portal imaging (EPI) and MV-CBCT, both per-formed in the same treatment session. EPI were compared with digitally reconstructed radiographies (DRRs). MV-CBCTs were matched to simulation CTs by manual registration based on bone markers (BMR), by manual registration based on soft tissues (STR) - rectum, bladder, and seminal vesicles - and by automatic registration (AR) performed by a mutual information algorithm. Shifts were evaluated along the three main axes: anteroposterior (AP), craniocaudal (CC), and laterolateral (LL). Finally, in 4 additional patients showing intraprostatic calcifications, the calcification mismatch error was used to evaluate the three MV-CBCT matching methods. RESULTS: A total of 50 pairs of orthogonal EPIs and 50 MV-CBCTs were analyzed. Assuming an overall tolerance of 2 mm, no significant differences were observed comparing EPI vs BMR in any axis. A significant difference (p < 0.001) was observed along the AP axis comparing EPI vs AR and EPI vs STR. On the calcification data set (22 measures), the calcification mismatch along the AP direction was significantly lower (p < 0.05) after STR than after BMR or AR. CONCLUSION: Bone markers were not an effective surrogate of the target position and significant differences were observed comparing EPI or BMR vs STR, supporting the assessment of soft tissue position by MVCBs to verify and correct patient setup in prostate radiotherapy.

Surgery and radiotherapy in the treatment of malignant parotid tumors: a retrospective multicenter study.

AIMS AND BACKGROUND: Major salivary gland cancers are rare, with many histologic types and subtypes. The low incidence and heterogeneity of primary parotid carcinomas makes their outcome difficult to evaluate. Treatment remains primarily surgical, but optimal therapeutic regimens have yet to be fully realized. The present study reviews the experience of three Italian institutions in the treatment of primary parotid carcinomas in order to describe the clinicopathological presentation and treatment options with emphasis on radiotherapy and to analyze the factors influencing survival. METHODS AND STUDY DESIGN: The records of 110 patients with primary parotid neoplastic lesions treated at three Italian institutions from 1993 to 2004 were retrospectively reviewed. Six patients were excluded from the study: 3 received surgery alone and 3 were not assessable, for a total of 104 assessable patients. Acute and late toxicity of radiotherapy was quantified following the recommendations of the RTOG/EORTC. Survival was analyzed by the actuarial Kaplan-Meier product-limit method. The influence of selected factors on 10-year disease-specific survival was analyzed. RESULTS: The 104 assessable patients were treated as follows: 11 patients received radiotherapy as their only treatment (3 with a palliative purpose) and 93 had postoperative radiotherapy. Thirty-two patients underwent neck dissection: neck lymph node metastases were found in all them. Their mean age was 60 years (range, 14-92). According to the UICC/2002 TNM Classification, 8 patients were stage I, 19 stage II, 34 stage III, 25 stage IVA, 5 stage IVB, 3 recurrent and 10 not assessable (Tx). The most frequent histologies were adenoid cystic carcinoma (n = 16), mucoepidermoid carcinoma (n = 15), and acinic cell carcinoma (n = 15). Twenty-three patients had recurrences: 10 had local recurrences, 3 neck recurrences, 9 distant metastases, and 1 patient had both local recurrence and distant metastases. No factors were observed that would negatively influence the prognosis. Actuarial 10-year disease-specific survival was 71% and actuarial 10-year local control 82%. CONCLUSIONS: The treatment of salivary gland malignancies remains primarily surgical. Our study confirms the results of the literature with surgery and adjunctive radiotherapy in patients with advanced-stage disease. No variables were observed to influence the prognosis.

Long term outcome of localized aggressive non-Hodgkin lymphoma treated with a short weekly chemotherapy regimen (doxorubicin, cyclophosphamide, bleomycin, vincristine, and prednisone) and involved field radiotherapy: result of a Gruppo Italiano Multiregionale per lo Studio dei Linfomi e Leucenie (GIMURELL) study.

Recently, management of limited stage diffuse large cell lymphoma (DLCL) is trending toward a low intensity chemotherapy approach. Since 1993 we have used a brief weekly (6 weeks) chemotherapy scheme (Doxorubicin, Cyclophosphamide, Bleomycin, Vincristine, and Prednisone = ACOP-B) followed by involved field radiotherapy in 207 consecutive patients with well defined localized DLCL without age limit (median 57 years, range 18-85). Treatment was completed as designed in 183 of 207 patients (88%). One hundred and ninety-nine patients (96%) achieved complete remission. At a median follow-up of 66 months 170 patients are alive (82%), 168 of them free of disease. Twenty-nine patients experienced relapse after achieving a complete remission. Kaplan-Meier, risk of relapse was 24% after 13 years. Thirty (14.5%) patients have died, 14 (6.8%) due to lymphoma progression, one due to regimen toxicity and 15 (7.2%) from other causes while remaining in complete remission. The probability of overall survival and event free survival at 13 years was 78% (95% CI 70-87%) and 63% (95% CI 50-75), respectively. Crude rate of secondary malignancy was 5.26 /1000 person-years. The ACOP-B regimen plus involved field radiotherapy is well tolerated both short and long term and is an effective chemotherapy scheme for very well defined limited stage aggressive non-Hodgkin lymphomas in all age categories.

Brain metastases from endometrial carcinoma: report of three cases and review of the literature.

AIMS AND BACKGROUND: Endometrial carcinoma is a rare cause of brain metastases, accounting for less than 1% of all metastatic lesions to the brain. This report aims to review our experience in the treatment of patients with brain metastases from endometrial carcinoma in order to establish the characteristics of these patients and evaluate the results and efficacy of whole-brain radiation therapy as a palliative measure. METHODS: Three cases of brain metastases from endometrial carcinoma treated with radiotherapy were identified in the files of the Division of Radiotherapy at the A. Businco Regional Oncological Hospital of Cagliari between 1999 and 2005. RESULTS: All patients had brain metastases as the only sign of systemic disease (a single lesion in 2 patients and 2 lesions in 1 patient). Two patients were classified as RTOG RPA class I and 1 patient as class III. Radiotherapy to the brain was delivered after surgical resection in the first 2 patients and as the only method of palliation in the third patient. The delivered radiation dose was 3000 cGy in 10 fractions over 2 weeks in the postoperative setting and 2000 cGy in 5 fractions over 1 week to the patient treated with irradiation alone. The 2 surgically treated patients are alive and well after 16 and 64 months, respectively. The patient treated with palliative intent died 2 months after irradiation. CONCLUSIONS: The combination of surgery and postoperative whole-brain irradiation in selected patients with solitary brain metastases from endometrial carcinoma is an effective method of palliation.

Results of whole brain radiation therapy in patients with brain metastases from colorectal carcinoma.

AIMS AND BACKGROUND: Carcinoma of the colon-rectum is an infrequent cause of brain metastases, constituting 1.5% of all metastatic lesions to the brain. We reviewed our experience in the treatment of brain metastases from colorectal cancer to define the efficacy of whole brain radiation therapy as a palliative measure in this setting of patients. METHODS: Twenty-three consecutive cases of brain metastasis from colorectal cancer treated between 1999 and 2004 were identified in the files of the Division of Radiotherapy of the A Businco Regional Oncological Hospital, Cagliari. Their records were reviewed for patient and tumor characteristics and categorized according to the RTOG RPA classes. RESULTS: Fifteen patients (65%) had multiple metastases. Twenty-one patients (91%) showed extracranial metastases. Fourteen patients were classified as RTOG RPA class II and 9 class III. The median radiation dose delivered was 2000 cGy in 5 fractions in one week (range, 20-36 Gy). In 14 of 20 assessable patients (70%), symptomatic improvement was observed. The median follow-up and survival time for all the patients, 12 females and 11 males, was 3 months. In 3 patients only the cause of death was the brain metastasis. CONCLUSIONS: Despite the disappointing survival time, external radiation therapy to the whole brain proved to be an efficacious palliative treatment for patients with multiple or inoperable brain metastasis from colorectal cancer.

Comparative evaluation of two hypofractionated radiotherapy regimens for painful bone metastases.

AIMS AND BACKGROUND: In 75% of the patients with bone metastases (BM) pain is the dominant symptom. Radiotherapy (XRT) plays a major role in the palliation of pain in patients with BM. Several schedules of short and long fractionation XRT are used in clinical practice, with hypofractionated treatments being even more attractive for practical reasons. A considerable body of evidence supports the clinical use of short schedules and single-dose XRT. We retrospectively evaluated the efficacy of two short fractionated schedules of 8 Gy as a single dose and 20 Gy in 5 fractions in relieving pain in patients with multiple uncomplicated BM. METHOD: From January to December 2001, 130 patients with 146 painful BM were treated with palliative localized XRT. There were 42 males and 88 females with a median age of 58 years (range 28-84). The commonest sites of treatment were the spine (59.6%) and pelvis (14.4%). The primary endpoint was clinically significant pain relief in the first six months of follow-up evaluated with the IAEA (International Atomic Energy Agency) pain measurement score measuring pain severity and pain frequency. Analgesic use was also recorded before and after treatment as drug frequency and drug severity. Patients with painful BM from any primary tumor site were irradiated. Treatment schedules consisted of a course of XRT with 4 Gy/fraction/day (total dose: 20 Gy/5 fractions) (group A, 59 lesions) or with a single dose of 8 Gy (group B, 87 lesions). RESULTS: There was no significant difference in complete response (CR) rates between treatment schedules: complete pain relief was achieved in 17/59 lesions (29%) in the fractionated group and in 29/87 lesions (33%) in the single-dose group. Also the overall response (complete + partial) was similar: 35/59 lesions (60%) in group A and 60/87 (69%) in group B. The minimum, maximum and median follow-up was 3, 23, and 9 months, respectively, for group A and 3, 20, and 11 months for group B. The actuarial median duration of pain relief was similar: 4.5 months in group A and 4 months in group B. No particular side effects were recorded in either group. CONCLUSIONS: There were no differences between the two fractionation schedules used in our study with regard to pain relief and use of analgesics. Palliation of pain was obtained in approximately two thirds of patients with both schedules, providing further evidence of the similar efficacy between single and multiple fractions. With regard to pain response these data justify a recommendation for the use of a more simple and convenient 8 Gy single fraction for the palliation of uncomplicated BM.