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1.  A review of the epidemiology and treatment of Merkel cell carcinoma 
Clinics  2011;66(10):1817-1823.
Merkel cell carcinoma is a very rare and aggressive neoplasm. Due to its rarity, therapeutic guidelines are not well established, especially for regionally advanced disease. Articles in English, French, Italian, Portuguese, and Spanish from the last 20 years were identified in MEDLINE and reviewed. The key word “Merkel” was used for the search, relevant articles were selected, and their references were examined. The most important articles related to epidemiology, genesis and treatment were reviewed. The incidence of Merkel cell carcinoma is increasing due to the advancing age of the population, higher rates of sun exposure and an increasing number of immunocompromised individuals. With regard to etiology, the recently described Merkel Cell polyomavirus is thought to play a role. Either local or regional surgical intervention remains the standard of care, but adjuvant radiotherapy or radiotherapy as a primary treatment have been discussed as reasonable therapeutic options. An update on this rare neoplasia is essential because of its increasing incidence and changing treatment options.
PMCID: PMC3180159  PMID: 22012057
Carcinoma, Merkel CELL; Literature review; Radiotherapy; Polyomavirus
2.  Neoadjuvant Chemoradiation Herapy for Soft Tissue Sarcomas of the Extremities 
Clinics (Sao Paulo, Brazil)  2009;64(11):1059-1064.
Neoadjuvant and adjuvant therapies for soft tissue sarcomas of the extremities are still controversial. The aim of this study was to analyze the results of a protocol of neoadjuvant chemoradiation therapy for extremity sarcomas.
A retrospective analysis was carried out in a consecutive series of 49 adult patients with advanced extremity soft tissue sarcomas that could not be resected with adequate margins during the primary resection. All patients were treated with a protocol of preoperative radiation therapy at a total dose of 30 Gy, concomitant with doxorubicin (60 mg/m2) chemotherapy. The main endpoints assessed were local recurrence-free survival, metastasis-free survival and overall survival. The median follow-up time was 32.1 months.
The five-year local recurrence-free survival, metastasis-free survival and overall survival rates were 81.5%, 46.7% and 58.3%, respectively. For high-grade tumors, the five-year metastasis-free and overall survival rates were only 36.3% and 41.2%, respectively. Severe wound complications were observed in 41.8% of the patients who underwent surgery. These complications precluded adjuvant chemotherapy in 73.7% (14/19) of the patients eligible to receive it.
In this study, neoadjuvant chemoradiation therapy was associated with a good local control rate, but the distant relapse-free rate and overall survival rate were still poor. The high rate of wound complications modified the planning of adjuvant treatment in most patients.
PMCID: PMC2780522  PMID: 19936179
Connective tissue neoplasms; Radiotherapy; Chemotherapy; Adjuvant treatment; Survival
3.  High-dose-rate brachytherapy for soft tissue sarcoma in children: a single institution experience 
To report our experience treating soft tissue sarcoma (STS) with high dose rate brachytherapy alone (HBRT) or in combination with external beam radiotherapy (EBRT) in pediatric patients.
Methods and materials
Eighteen patients, median age 11 years (range 2 – 16 years) with grade 2–3 STS were treated with HBRT using Ir-192 in a interstitial (n = 14) or intracavitary implant (n = 4). Eight patients were treated with HBRT alone; the remaining 10 were treated with a combination of HBRT and EBRT.
After a median follow-up of 79.5 months (range 12 – 159), 14 patients were alive and without evidence of disease (5-year overall survival rate 84.5%). There were no local or regional failures in the group treated with HBRT alone. One patient developed distant metastases at 14 months and expired after 17 months. In the combined HBRT and EBRT group, there was 1 local failure (22 months), and 3 patients developed pulmonary metastatic disease 18, 38 and 48 months after diagnosis and no these patients were alive at the time of this report. The overall local control to HBRT alone and HBRT plus EBRT were 100 and 90%, respectively. The acute affects most common were local erythema and wound dehiscence in 6 (33%) and 4 (22%) patients.
Late effects were observed in 3 patients (16.5%).
Excellent local control with tolerable side effects have been observed in a small group of paediatric patients with STS treated by HBRT alone or in combination with EBRT.
PMCID: PMC2359754  PMID: 18423047
4.  The relationship between the biochemical control outcomes and the quality of planning of high-dose rate brachytherapy as a boost to external beam radiotherapy for locally and locally advanced prostate cancer using the RTOG-ASTRO Phoenix definition 
Purpose: To evaluated prognostic factors and impact of the quality of planning of high dose rate brachytherapy (HDR-BT) for patients with local or locally advanced prostate cancer treated with external beam radiotherapy (EBRT) and HDR-BT.
Methods and Materials: Between 1997 and 2005, 209 patients with biopsy proven prostate adenocarcinoma were treated with localized EBRT and HDR-BT at the Department of Radiation-Oncology, Hospital A. C. Camargo, Sao Paulo, Brazil. Patient's age, Gleason score (GS), clinical stage (CS), initial PSA (iPSA), risk group for biochemical failure (GR), doses of EBRT and HDR-BT, use of three-dimensional planning for HDR-BT (3DHDR) and the Biological Effective Dose (BED) were evaluated as prognostic factors for biochemical control (bC).
Results: Median age and median follow-up time were 68 and 5.3 years, respectively. Median EBRT and HDR-BT doses were 45 Gy and 20 Gy. The crude bC at 3.3 year was 94.2%. For the Low, intermediate and high risk patients the bC rates at 3.3 years were 91.5%, 90.2% and 88.5%, respectively. Overall survival (OS) and disease specific survival rates at 3.3 years were 97.8% and 98.4%, respectively. On univariate analysis the prognostic factors related bC were GR (p= 0.040), GS ≤ 6 (p= 0.002), total dose of HDR-BT ≥ 20 Gy (p< 0.001), 3DHDR (p< 0.001), BED-HDR ≥ 99 Gy1.5 (p<0.001) and BED-TT ≥ 185 (p<0.001). On multivariate analysis the statistical significant predictive factors related to bC were RG (p< 0.001), HDR-BT ≥ 20 Gy (p=0.008) and 3DHDR (p<0.001).
Conclusions: we observed that the bC rates correlates with the generally accepted risk factors described in the literature. Dose escalation, evaluated through the BED, and the quality of planning of HDR-BT are also important predictive factors when treating prostate cancer.
PMCID: PMC2424177  PMID: 18566673
high-dose rate brachytherapy; external beam radiotherapy; prostate cancer; RTOG-ASTRO Phoenix; biochemical failure; biochemical control
5.  Whole brain radiotherapy for brain metastases from breast cancer: estimation of survival using two stratification systems 
BMC Cancer  2007;7:53.
Brain metastases (BM) are the most common form of intracranial cancer. The incidence of BM seems to have increased over the past decade. Recursive partitioning analysis (RPA) of data from three Radiation Therapy Oncology Group (RTOG) trials (1200 patients) has allowed three prognostic groups to be identified. More recently a simplified stratification system that uses the evaluation of three main prognostics factors for radiosurgery in BM was developed.
To analyze the overall survival rate (OS), prognostic factors affecting outcomes and to estimate the potential improvement in OS for patients with BM from breast cancer, stratified by RPA class and brain metastases score (BS-BM). From January 1996 to December 2004, 174 medical records of patients with diagnosis of BM from breast cancer, who received WBRT were analyzed. The surgery followed by WBRT was used in 15.5% of patients and 84.5% of others patients were submitted at WBRT alone; 108 patients (62.1%) received the fractionation schedule of 30 Gy in 10 fractions. Solitary BM was present in 37.9 % of patients. The prognostic factors evaluated for OS were: age, Karnofsky Performance Status (KPS), number of lesions, localization of lesions, neurosurgery, chemotherapy, absence extracranial disease, RPA class, BS-BM and radiation doses and fractionation.
The OS in 1, 2 and 3 years was 33.4 %, 16.7%, and 8.8 %, respectively. The RPA class analysis showed strong relation with OS (p < 0.0001). The median survival time by RPA class in months was: class I 11.7, class II 6.2 and class III 3.0. The significant prognostic factors associated with better OS were: higher KPS (p < 0.0001), neurosurgery (P < 0.0001), single metastases (p = 0.003), BS-BM (p < 0.0001), control primary tumor (p = 0.002) and absence of extracranial metastases (p = 0.001). In multivariate analysis, the factors associated positively with OS were: neurosurgery (p < 0.0001), absence of extracranial metastases (p <0.0001) and RPA class I (p < 0.0001).
Our data suggests that patients with BM from breast cancer classified as RPA class I may be effectively treated with local resection followed by WBRT, mainly in those patients with single BM, higher KPS and cranial extra disease controlled. RPA class was shown to be the most reliable indicators of survival.
PMCID: PMC1851018  PMID: 17386108
6.  Salvage radiotherapy for biochemical relapse after complete PSA response following radical prostatectomy: outcome and prognostic factors for patients who have never received hormonal therapy 
To evaluate the results of salvage conformal radiation therapy (3DC-EBRT) for patients submitted to radical prostatectomy (RP) who have achieved complete PSA response and who have never been treated with hormonal therapy (HT).
To present the results of biochemical control, a period free from hormonal therapy and factors related to its prognosis.
Materials and methods
from August 2002 to December 2004, 43 prostate cancer patients submitted to RP presented biochemical failure after achieving a PSA < 0.2 ng/ml. They have never received HT and were submitted to salvage 3DC-EBRT. Median age was 62 years, median preoperative PSA was 8.8 ng/ml, median Gleason Score was 7. Any PSA rise above 0.2 was defined as biochemical failure after surgery. Median 3DC-EBRT dose was 70 Gy, biochemical failure after EBRT was defined as 3 consecutive rises in PSA or a single rise enough to trigger HT.
3-year biochemical non-evidence of disease (BNED) was 71%. PSA doubling time lower than 4 months (p = 0.01) and time from recurrence to salvage EBRT (p = 0.04) were associated with worse chance of biochemical control. Biochemical control of 76% was achieved when RT had been introduced with a PSA lower than 1 ng/ml vs. 48% with a PSA higher than 1 (p = 0.19). Late toxicity was acceptable.
70% of biochemical control in 3 years can be achieved with salvage radiotherapy in selected patients. The importance of PSADT was confirmed in this study and radiotherapy should be started as early as possible. Longer follow up is necessary, but it is possible to conclude that a long interval free from hormonal therapy was achieved with low rate of toxicity avoiding or at least delaying several important adverse effects related to hormonal treatment.
PMCID: PMC1820601  PMID: 17316430
7.  Preoperative external beam radiotherapy and reduced dose brachytherapy for carcinoma of the cervix: survival and pathological response 
To evaluate the pathologic response of cervical carcinoma to external beam radiotherapy (EBRT) and high dose rate brachytherapy (HDRB) and outcome.
Materials and methods
Between 1992 and 2001, 67 patients with cervical carcinoma were submitted to preoperative radiotherapy. Sixty-five patients were stage IIb. Preoperative treatment included 45 Gy EBRT and 12 Gy HDRB. Patients were submitted to surgery after a mean time of 82 days. Lymphadenectomy was performed in 81% of patients. Eleven patients with residual cervix residual disease on pathological specimen were submitted to 2 additional insertions of HDRB.
median follow up was 72 months. Five-year cause specific survival was 75%, overall survival 65%, local control 95%. Complete pelvic pathological response was seen in 40%. Surgery performed later than 80 days was associated with pathological response. Pelvic nodal involvement was found in 12%. Complete pelvic pathological response and negative lymphnodes were associated with better outcome (p = .03 and p = .005). Late grade 3 and 4 urinary and intestinal adverse effects were seen in 12 and 2% of patients.
Time allowed between RT and surgery correlated with pathological response. Pelvic pathological response was associated with improved outcome. Postoperative additional HDRB did not improve therapeutic results. Treatment was well tolerated.
PMCID: PMC1817645  PMID: 17316435
8.  Salvage for cervical recurrences of head and neck cancer with dissection and interstitial high dose rate brachytherapy 
Salvage therapy in head and neck cancer (HNC) is a controversy issue and the literature is scarce regarding the use of interstitial high-dose rate brachytherapy (I-HDR) in HNC. We evaluated the long-term results of a treatment policy combining salvage surgery and I-HDR for cervical recurrences of HNC. Charts of 21 patients treated from 1994 to 2004 were reviewed. The crude local control rate for all patients was 52.4%. The 5- and 8-years overall (OS) and local relapse-free survival (LRFS) rates were 50%, 42.9%, 42.5% and 28.6%, respectively. The only predictive factor associated to LFRS and OS was negative margin status (p = 0.0007 and p = 0.0002). We conclude that complete surgery is mandatory for long term control and the doses given by brachytherapy are not high enough to compensate for microscopic residual disease after surgery.
PMCID: PMC1559626  PMID: 16895605

Results 1-8 (8)