Metformin and statins: a possible role in high-risk prostate cancer.

AIM AND BACKGROUND: There is increasing evidence that statins and oral anti-diabetic drugs, such as metformin, can have a favorable role in advanced prostate cancer treatment.Metformin has been shown to inhibit proliferation of tumor cells in vitro and statins inhibit carcinogenesis by suppressing angiogenesis/invasion mechanisms. However, clinical evidence on the protective effect of these drugs is still weak.The purpose of this study is to analyze if these drugs have an impact on Biochemical-Failure-Free-Survival (BFFS) and on Distant-Failure-Free-Survival (DFFS) in localized high-risk prostate cancer. MATERIAL AND METHODS: From 2002-2016, 447 patients with histologically confirmed high-risk prostate cancer were retrospectively evaluated. All patients received radiotherapy and androgen deprivation therapy. Biochemical recurrence was determined by the Phoenix criteria and metastatic patients were defined by the presence of radiological metastasis. Survival analysis was performed using the Kaplan-Meier method. RESULTS: 175 patients were treated with statins (65.3 % with a dose ≤ 20 mg/day) and 70 with metformin (75.7 % with a dose ≤ 1700 mg/day). Median follow-up was 88 months (1-194) with no differences in BFFS and DFFS between metformin and non-metformin patients (77.4 % versus 80 %, p = 0.91 and 89.4 % versus 88.7 %, p = 0.56, respectively). We did not find a statistical difference in BFFS and DFFS in patients taking higher doses of those drugs. CONCLUSION: Metformin and statins were not associated with BFFS or DFFS improvement in our analysis. However, the small number of patients treated with these drugs limits the reliability of the results and prospective studies are needed.

Multidisciplinary approach in stage III non-small-cell lung cancer: standard of care and open questions.

Lung cancer is the most frequent cause of cancer death worldwide and its global incidence has been steadily increasing during recent decades. A third of patients with newly diagnosed non-small-cell lung cancer (NSCLC) present with locally advanced disease. There is not a single widely accepted standard of care for these patients because of the wide spectrum of presentation of the disease. Although feasible and safe in experienced hands, evidence that surgical resection after induction treatment improves overall survival (OS) is lacking. For resectable or potentially resectable stage III, the findings of two phase III trials suggest that surgical resection should not be considered a standard of care but rather reserved for selected patients after critical multidisciplinary assessment, in whom surgery improves survival after downstaging if pneumonectomy can be avoided or in some T4N0-1 resectable tumours. For unresectable stage III NSCLC the standard of care is a combination of chemotherapy and radiotherapy. In those patients with good performance status and minimal weight loss, the concurrent approach has resulted in a statistically significant improvement in OS rates compared with a sequential approach in randomised clinical trials, although several questions remain unresolved.

Superoxidase dismutase (SOD) topical use in oncologic patients: treatment of acute cutaneous toxicity secondary to radiotherapy.

OBJECTIVE: The objective of this study is to evaluate the efficiency of SOD applied topically in oncologic patients affected by acute radiodermatitis. MATERIALS AND METHOD: This study includes 57 patients who showed a dermatitis grade 2 or superior; they were administered SOD ointment b.i.d. (40 mg, weekly) and follow-up continued for 12 weeks. RESULTS: At the end of radiotherapy, 77.1% of the patients ameliorated completely or partially, and at the end of the 12-week period 100% of patients were free of toxicity. No acute toxicity relapses were reported. Response time reduced during radiotherapy, as well as the treatment time at the end of it. CONCLUSIONS: The employment of SOD topically is efficient in the treatment of radiodermatitis, which is an acute side effect of radiotherapy.

[The role of transrectal ultrasound on prostatic cryotherapy and brachytherapy]. / Papel de la ecografía transrectal en crioterapia y braquiterapia prostáticas.

OBJECTIVES: Transrectal ultrasound is the method that gives a direct image of the prostate, its limits, structural and morphologic anomalies, and anatomical relations. Therefore, prostate volume is easily determined, being the first step for the application of certain therapeutic procedures. Prostatic cryotherapy and brachytherapy have been developed over the last years as minimally invasive options for the treatment of prostate cancer. Transrectal ultrasound of the prostate has allowed the application of these technologies in the daily practice, guaranteeing high efficacy and safety indexes. Cryosurgery is the controlled freezing of tissues. Prostatic transrectal ultrasound is the only method able to show the real-time evolution of prostatic cryoablation, allowing the urologist to control the evolution of the ice ball and to reach the targeted anatomical structures guaranteeing the oncological objectives, and diminishing complications and sequels. Brachytherapy, as a local intraprostatic radiotherapy, needs exact volume and dose calculations before the implant of the radioactive source within the gland. With transrectal ultrasound of the prostate, ultrasound-tomographic cuts are made for prostatic volume calculation and planimetry Once dosimetry is completed, real-time transrectal ultrasound control is necessary to perform the implant of the needles loaded with the seeds. Today, prostate cryotherapy and brachytherapy would be inconceivable without transrectal ultrasound.

Papel de la ecografía transrectal en crioterapia y braquiterapia prostáticas / The role of transrectal ultrasound on prostatic cryotherapy and brachytherapy

OBJETIVO La ecografía transrectal es el método que proporciona una imagen directa de la próstata, sus límites, alteraciones estructurales y morfológicas y relaciones anatómicas. El volumen prostático es, en consecuencia, fácil de determinar, siendo el primer paso necesario para la aplicación de determinados procedimientos terapéuticos. La crioterapia y la braquiterapia prostáticas se han desarrollado en los últimos años como opciones mínimamente invasivas para el tratamiento del cáncer de próstata. La ecografía transrectal de próstata ha permitido la aplicación de estas tecnologías en la práctica diaria garantizando altos índices de eficacia y seguridad. La criocirugía es la congelación controlada de los tejidos. La ecografía transrectal de próstata es el único método capaz de reflejar en tiempo real la evolución de la crioablación prostática, permitiendo al urólogo controlar la evolución de la bola de hielo y alcanzar las estructuras anatómicas deseadas garantizando los objetivos oncológicos y disminuyendo la aparición de complicaciones y secuelas. La braquiterapia como forma de radioterapia local intraprostática necesita de cálculos volumétricos y dosimétricos exactos previos a la implantación de la fuente radioactiva en el interior de la glándula. Con ecografía transrectal de próstata se realizan cortes ecotomográficos para el cálculo del volumen y planimetría prostáticos. Una vez realizada la dosimetría y para realizar el implante de las agujas cargadas con las semillas en su lugar exacto es necesario el control con ecografía transrectal en tiempo real. Hoy en día la crioterapia y braquiterapia prostáticas serían inconcebibles sin la ecografía transrectal

OBJECTIVES: Transrectal ultrasound is the method that gives a direct image of the prostate, its limits, structural and morphologic anomalies, and anatomical relations. Therefore, prostate volume is easily determined, being the first step for the application of certain therapeutic procedures. Prostatic cryotherapy and brachytherapy have been developed over the last years as minimally invasive options for the treatment of prostate cancer. Transrectal ultrasound of the prostate has allowed the application of these technologies in the daily practice, guaranteeing high efficacy and safety indexes. Cryosurgery is the controlled freezing of tissues. Prostatic transrectal ultrasound is the only method able to show the real-time evolution of prostatic cryoablation, allowing the urologist to control the evolution of the ice ball and to reach the targeted anatomical structures guaranteeing the oncological objectives, and diminishing complications and sequels. Brachytherapy, as a local intraprostatic radiotherapy, needs exact volume and dose calculations before the implant of the radioactive source within the gland. With transrectal ultrasound of the prostate, ultrasound-tomographic cuts are made for prostatic volume calculation and planimetry. Once dosimetry is completed, real-time transrectal ultrasound control is necessary to perform the implant of the needles loaded with the seeds. Today, prostate cryotherapy and brachytherapy would be inconceivable without transrectal ultrasound

Once-weekly dose of epoetinum alfa in cancer patients with anemia receiving radiotherapy

Introduction. Anaemia is present in 30%-90% of all patients with cancer, and its origin is multifactorial. Human recombinant erythropoietin has been shown to be useful in treating anemia in patients with cancer. The aim of this study was to evaluate the effectiveness of treatment of anaemia with epoetin alfa (EPO) given as a single weekly dose, and its repercussions on quality of life (QoL). Materials and methods. From January to October 2002, a total of 139 patients referred to our service for radiotherapy (RT) had anemia and received treatment with EPO as a single weekly dose of 40,000 IU subcutaneously, with oral iron supplement. If haemoglobin (Hb) values after 1 month of treatment did not increase by >=1 g/dl, the dose was increased to 60,000 IU/week. Treatment with EPO ended when Hb values reached >=14 g/dl or one month after the end of RT regardless of Hb values. QoL was evaluated with the Functional Assessment of Cancer Therapy-Anaemia subscale (FACT-An) and the Cancer Linear Analogue Scale (CLAS). Results. Mean Hb at the start of treatment with EPO was 11.49 ± 1.08 g/dl, and the mean value at the end of treatment was 14.52 ± 1.41 g/dl (p < 0.001). The mean increase in Hb was 2.97 ± 1.65 g/dl. Mean duration of treatment was 7.13 ± 2.91 weeks. In 11 patients (7.9%) the dose was increased after 4 weeks. In 84 patients (60.4%) EPO treatment was implemented before the commencing of RT. Mean Hb values in this group was 11.34 ± 1.11 g/dl at the start of EPO treatment, 12.69 ± 1.56 g/dl at the start of RT, 13.96 ± 1.54 g/dl at the end of RT and 14.68 ± 1.3 g/dl at the end of EPO treatment (p < 0.001). In 55 patients (39.6%) anaemia developed during RT and, therefore, EPO treatment was implemented after commencing of RT. In this group the mean Hb values were 12.29 ± 1.6 g/dl at the start of RT, 11.72 ± 1.01 g/dl at the start of EPO treatment, 13.97 ± 1.53 g/dl at the end of RT and 14.28 ± 1.54 g/dl at the end of EPO treatment (p < 0.001). Hemoglobin levels at the start of EPO were lower in patients who commenced EPO before RT (p < 0.05). In 60 patients who received combined RT and chemotherapy, mean Hb values were 11.42 ± 1.16 g/dl at the start of EPO and 13.98 ± 1.55 g/dl at the end of EPO (p < 0.005). In 75 patients who had received RT alone, the mean Hb values was 11.53 ± 1.05 g/dl at the start of EPO and 14.98 ± 1.17 g/dl at the end of treatment (p < 0.001). Patients treated with RT alone had higher Hb levels at the end of RT and at the end of EPO treatment than did patients who had received combined treatment (p < 0.005). The duration of EPO treatment was shorter in the group treated with RT alone than in the combined treatment group (6.41 ± 2.99 weeks versus 7.96 ± 2.67 weeks; p < 0.005). No significant differences were observed in FACT-An and CLAS scores at the beginning and the end of the study. Conclusions. Treatment with epoetin alfa as a single weekly dose significantly increased Hb levels in patients with cancer who were undergoing radiotherapy. The response was greater in patients treated with radiotherapy alone than in those receiving combined therapy. The duration of EPO treatment was shorter in the group treated with radiotherapy alone than in the combined treatment group

Early stage breast cancer conserving treatment: high dose rate brachytherapy boost to the tumour bed.

INTRODUCTION: The dose administered to the tumour bed is a risk-factor for local recurrence in localised breast cancer following breast-conserving surgery. MATERIALS AND METHODS: All patients (n=94) received 50 Gy external beam radiotherapy and one application of 700 cGy at 85% isodose with high dose rate brachytherapy. RESULTS: Of the cases, 84% were infiltrating ductal carcinoma; 31.2% were G3; 28% were intraductal component > 25%; 54% had margin < 1 cm or unknown. With a mean follow-up of 65 months (range: 36-107 months), the overall actuarial survival at 5 and 8 years was 93.2% and 84.2%, respectively; disease-free survival was 88.3% and 84.6%, respectively; local control was 92.2% and 88.75%, respectively. Local recurrence rate was 5.3%, and distant dissemination rate was 8.5%. Among the risk-factors analysed, only the presence of 4 or more lymph node involvement implied a higher risk for local recurrence (p =0.0001). For distant dissemination, the risk-factors were: 4 or more lymph nodes involved (p = 0.0001),G3 (p =0.029), tumour >3 cm (p = 0.001), irradiation volume with external beam radiotherapy (p =0.0001), and presence of local recurrence (p = 0.001). CONCLUSION: High dose rate brachytherapy is an effective method for reducing local recurrence, and increasing local control.

Early stage breast cancer conserving treatment: high dose rate brachytherapy boost to the tumour bed

Introduction. The dose administered to the tumour bed is a risk-factor for local recurrence in localised breast cancer following breast-conserving surgery. Materials and Methods. All patients (n=94) received 50 Gy external beam radiotherapy and one application of 700 cGy at 85% isodose with high dose rate brachytherapy. Results. Of the cases, 84% were infiltrating ductal carcinoma; 31.2% were G3; 28% were intraductal component > 25%; 54% had margin 3 cm (p = 0.001), irradiation volume with external beam radiotherapy (p = 0.0001), and presence of local recurrence (p = 0.001). Conclusion. High dose rate brachytherapy is an effective method for reducing local recurrence, and increasing local control

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