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1.  Local control after radiosurgery for brain metastases: predictive factors and implications for clinical decision 
To evaluate the local control of brain metastases (BM) in patients treated with stereotactic radiosurgery (SRS), correlate the outcome with treatment parameters and lesion characteristics, and define its implications for clinical decisions.
Between 2007 and 2012, 305 BM in 141 consecutive patients were treated with SRS. After exclusions, 216 BM in 100 patients were analyzed. Doses were grouped as follows: ≤15 Gy, 16–20 Gy, and ≥21 Gy. Sizes were classified as ≤10 mm and >10 mm. Local control (LC) and overall survival (OS) were estimated using the Kaplan-Meier method. Log-rank statistics were used to identify the prognostic factors affecting LC and OS. For multivariate analyses, a Cox proportional model was applied including all potentially significant variables reached on univariate analyses.
Median age was 54 years (18–80). Median radiological follow-up of the lesions was 7 months (1–66). Median LC and the LC at 1 year were 22.3 months and 69.7%, respectively. On univariate analysis, tumor size, SRS dose, and previous whole brain irradiation (WBRT) were significant factors for LC. Patients with lesions >10 and ≤10 mm had an LC at 1 year of 58.6% and 79.1%, respectively (p = 0.008). In lesions receiving ≤15 Gy, 16–20 Gy, and ≥21 Gy, the 1-year LC rates were 39.6%, 71.7%, and 92.3%, respectively (p < 0.001). When WBRT was done previously, LC at 1 year was 57.9% compared with 78.4% for those who did not undergo WBRT (p = 0.004). On multivariate analysis, dose remained the single most powerful prognostic factor for LC. Median OS for all patients was 17 months, with no difference among the groups.
Dose is the most important predictive factor for LC of BM. Doses below 16 Gy correlated with poor LC. The SRS dose as salvage treatment after previous WBRT should not be reduced unless there is a pressing reason to do so.
PMCID: PMC4353457  PMID: 25884621
Radiosurgery; Brain Metastases; Whole-Brain Radiotherapy
2.  Adjuvant chemoradiotherapy after d2-lymphadenectomy for gastric cancer: the role of n-ratio in patient selection. results of a single cancer center 
Adjuvant chemoradiotherapy is part of a multimodality treatment approach in order to improve survival outcomes after surgery for gastric cancer. The aims of this study are to describe the results of gastrectomy and adjuvant chemoradiotherapy in patients treated in a single institution, and to identify prognostic factors that could determine which individuals would benefit from this treatment.
This retrospective study included patients with pathologically confirmed gastric adenocarcinoma who underwent surgical treatment with curative intent in a single cancer center in Brazil, between 1998 and 2008. Among 327 patients treated in this period, 142 were selected. Exclusion criteria were distant metastatic disease (M1), T1N0 tumors, different multimodality treatments and tumors of the gastric stump. Another 10 individuals were lost to follow-up and there were 3 postoperative deaths. The role of several clinical and pathological variables as prognostic factors was determined.
D2-lymphadenectomy was performed in 90.8% of the patients, who had 5-year overall and disease-free survival of 58.9% and 55.7%. The interaction of N-category and N-ratio, extended resection and perineural invasion were independent prognostic factors for overall and disease-free survival. Adjuvant chemoradiotherapy was not associated with a significant improvement in survival. Patients with node-positive disease had improved survival with adjuvant chemoradiotherapy, especially when we grouped patients with N1 and N2 tumors and a higher N-ratio. These individuals had worse disease-free (30.3% vs. 48.9%) and overall survival (30.9% vs. 71.4%).
N-category and N-ratio interaction, perineural invasion and extended resections were prognostic factors for survival in gastric cancer patients treated with D2-lymphadenectomy, but adjuvant chemoradiotherapy was not. There may be some benefit with this treatment in patients with node-positive disease and higher N-ratio.
PMCID: PMC3542168  PMID: 23068190
3.  High-dose-rate brachytherapy combined with hypofractionated external beam radiotherapy for men with intermediate or high risk prostate cancer: analysis of short- and medium-term urinary toxicity and biochemical control 
The best management of localized and locally advanced prostate cancer remains controversial, but there are clinical evidences that for patients considered of unfavorable outcome that dose escalation radiotherapy has a significantly better outcome. Methods: Between 2005-2009 a total of 39 unfavorable patients were treated in a phase I-II trial for dose escalation with high-dose rate (HDR)- 30 Gy given by 4 fractions BID, in two separated implants and hypofractionated conformal/tri-dimensional radiotherapy (hEBRT) - 45 Gy (3 Gy per fraction in 3 weeks), at Hospital AC Camargo, Sao Paulo, Brazil. Results: Median age of patients was 69 (range, 58-80) years old. With a median follow up of 42.5 months the highest RTOG acute severe genitourinary toxicity (GU-TX) was grade 3 in two (5.1%) patients. Late severe GU-TX was observed in one (2.6%) patient. On univariate analysis the prostate volume > 45cc (p=0.024), <11 needles per implant (p=0.038) and urethral dose >130% of prescribed dose (p<0,001) were statistical significant predictive factors. Multivariate analysis showed urethral dose >130% as the only predictive factor for late severe GU-TX, p=0.017 (95%CI-1.39-29.49), HR-6.4. The actuarial overall survival, biochemical control and disease specific survival rates for the entire group at 3.5-years were 92.0%, 87.6% and 96.9%, respectively. Conclusion: HDR combined to hEBRT is well tolerated in the short and medium term. Acute toxicity was minimal and improved outcomes in terms of reduced late toxicity can be achieved using at least 11 needles and prostate with no more than 45cc to be implanted. The maximum urethral dose should be kept bellow 130% of prescribed dose.
PMCID: PMC3048983  PMID: 21394285
Prostate cancer; radiotherapy; brachytherapy; toxicity; biochemical control
4.  Conformal radiotherapy for lung cancer: interobservers' variability in the definition of gross tumor volume between radiologists and radiotherapists 
Conformal external radiotherapy aims to improve tumor control by boosting tumor dose, reducing morbidity and sparing healthy tissues. To meet this objective careful visualization of the tumor and adjacent areas is required. However, one of the major issues to be solved in this context is the volumetric definition of the targets. This study proposes to compare the gross volume of lung tumors as delineated by specialized radiologists and radiotherapists of a cancer center.
Chest CT scans of a total of 23 patients all with non-small cell lung cancer, not submitted to surgery, eligible and referred to conformal radiotherapy on the Hospital A. C. Camargo (São Paulo, Brazil), during the year 2004 were analyzed. All cases were delineated by 2 radiologists and 2 radiotherapists. Only the gross tumor volume and the enlarged lymph nodes were delineated. As such, four gross tumor volumes were achieved for each one of the 23 patients.
There was a significant positive correlation between the 2 measurements (among the radiotherapists, radiologists and intra-class) and there was randomness in the distribution of data within the constructed confidence interval.
There were no significant differences in the definition of gross tumor volume between radiologists and radiotherapists.
PMCID: PMC2732918  PMID: 19653915
5.  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
6.  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
7.  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
8.  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
9.  Intensity Modulated Radiotherapy (IMRT) in the postoperative treatment of an adenocarcinoma of the endometrium complicated by a pelvic kidney 
Pelvic Radiotherapy (RT) as a postoperative treatment for endometrial cancer improves local regional control. Brachytherapy also improves vaginal control. Both treatments imply significant side effects that a fine RT technique can help avoiding. Intensity Modulated RT (IMRT) enables the treatment of the target volume while protecting normal tissue. It therefore reduces the incidence and severity of side effects.
We report on a 50 year-old patient with a serous-papiliferous adenocarcinoma of the uterus who was submitted to surgical treatment without lymph node sampling followed by Brachytherapy, and Chemotherapy. The patient had a pelvic kidney, and was therefore treated with IMRT.
So far, the patient has been free from relapse and with normal kidney function.
IMRT is a valid technique to prevent the kidney from radiation damage.
PMCID: PMC1660561  PMID: 17116263
10.  Chemotherapy followed by low dose radiotherapy in childhood Hodgkin's disease: retrospective analysis of results and prognostic factors 
To report the treatment results and prognostic factors of childhood patients with Hodgkin's disease treated with chemotherapy (CT) followed by low dose radiotherapy (RT).
Patients and methods
This retrospective series analyzed 166 patients under 18 years old, treated from January 1985 to December 2003. Median age was 10 years (range 2–18). The male to female ratio was 2,3 : 1. Lymphonode enlargement was the most frequent clinical manifestation (68%), and the time of symptom duration was less than 6 months in 55% of the patients. In histological analysis Nodular Sclerosis was the most prevalent type (48%) followed by Mixed Celularity (34.6%). The staging group according Ann Arbor classification was: I (11.7%), II (36.4%), III (32.1%) and IV (19.8%). The standard treatment consisted of chemotherapy multiple drug combination according the period of treatment protocols vigent: ABVD in 39% (n-65) of the cases, by VEEP in 13 %(n-22), MOPP in 13 %(n-22), OPPA-13 %(n-22) and ABVD/OPPA in 22 %(n-33). Radiotherapy was device to all areas of initial presentation of disease. Dose less or equal than 21 Gy was used in 90.2% of patients with most part of them (90%) by involved field (IFRT) or mantle field.
The OS and EFS in 10 years were 89% and 87%. Survival according to clinical stage as 94.7%, 91.3%, 82.3% and 71% for stages I to IV(p = 0,005). The OS was in 91.3% of patients who received RT and in 72.6% of patients who did not (p = 0,003). Multivariate analysis showed presence of B symptoms, no radiotherapy and advanced clinical stage to be associated with a worse prognosis.
This data demonstrating the importance of RT consolidation with low dose and reduced volume, in all clinical stage of childhood HD, producing satisfactory ten years OS and EFS. As the disease is highly curable, any data of long term follow-up should be presented in order to better direct therapy, and to identify groups of patients who would not benefit from radiation treatment.
PMCID: PMC1592540  PMID: 17014708
11.  High-risk surgical stage 1 endometrial cancer: analysis of treatment outcome 
To report the relapse and survival rates associated to treatment for patients with stage IC, grade 2 or grade 3 and IB grade 3 diseases considered high risk patients group for relapse.
Materials and methods
From January 1993 to December 2003, 106 patients with endometrial cancer stage I were managed surgically in our institution. Based on data from the medical records, 106 patients with epithelial endometrial cancer met the following inclusion criteria: stage IC grade 2 or 3 and IB grade 3 with or without lymphovascular invasion. Staging was defined according to the FIGO surgical staging system. Postoperative adjuvant radiotherapy consisted of external beam pelvic radiation, vaginal brachytherapy alone or both. The median age was 65 years (range, 32–83 years), lymph node dissection was performed in 45 patients (42.5%) and 14 patients (13.2%) received vaginal brachytherapy only, and 92 (86.8%) received combined vaginal brachytherapy and external beam radiotherapy. The median dose of external beam radiotherapy administered to the pelvis was 4500 cGy (range 4000 – 5040). The median dose to vaginal surface was 2400 cGy (range 2000 – 3000). Predominant pathological stage and histological grade were IC (73.6%) and grade 3 (51.9%). The lymphovascular invasion was present in 33 patients (31.1%) and pathological stage IC grade 2 was most common (48. 1%) combination of risk factors in this group.
With a follow up median of 58.3 months (range 12.8 – 154), five year overall survival and event free survival were 78.5% and 72.4%, respectively. Locoregional control in five year was 92.4%. Prognostic factors related with survival in univariate analyses were: lymphadenectomy (p = 0.045), lymphovascular invasion (p = 0.047) and initial failure site (p < 0.0001). In multivariate analyses the initial failure in distant sites (p < 0.0001) was the only factor associated with poor survival. Acute and chronic gastrointestinal and genitourinary toxicity grades 3 were not observed.
In conclusion, our results showed that the stage IC, grade 2, 3 and IB grade 3 endometrial cancer was associated with significantly increased risk of distant relapse and endometrial carcinoma-related death independently of salvage treatment modality.
PMCID: PMC1555589  PMID: 16887018
12.  Whole brain radiation therapy in management of brain metastasis: results and prognostic factors 
To evaluate the prognostic factors associated with overall survival in patients with brain metastasis treated with whole brain radiotherapy (WBRT) and estimate the potential improvement in survival for patients with brain metastases, stratified by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class.
Patients and methods
From January 1996 to December 2000, 270 medical records of patients with diagnosis of brain metastasis, who received WBRT in the Hospital do Cancer Sao Paulo A.C. Camargo in the period, were analyzed. The surgery followed by WBRT was used in 15% of patients and 85 % of others patients were submitted at WBRT alone; in this cohort 134 patients (50%) received the fractionation schedule of 30 Gy in 10 fractions. The most common primary tumor type was breast (33%) followed by lung (29%), and solitary brain metastasis was present in 38.1% of patients. The prognostic factors evaluated for overall survival were: gender, age, Karnofsky Performance Status (KPS), number of lesions, localization of lesions, primary tumor site, surgery, chemotherapy, absence extracranial disease, RPA class and radiation doses and fractionation.
The OS in 1, 2 and 3 years was 25, 1%, 10, 4% e 4, 3% respectively, and the median survival time was 4.6 months. The median survival time in months according to RPA class after WBRT was: 6.2 class I, 4.2 class II and 3.0 class III (p < 0.0001). In univariate analysis, the significant prognostic factors associated with better survival were: KPS higher than 70 (p < 0.0001), neurosurgery (p < 0.0001) and solitary brain metastasis (p = 0.009). In multivariate analysis, KPS higher than 70 (p < 0.001) and neurosurgery (p = 0.001) maintained positively associated with the survival.
In this series, the patients with higher perform status, RPA class I, and treated with surgery followed by whole brain radiotherapy had better survival.
This data suggest that patients with cancer and a single metastasis to the brain may be treated effectively with surgical resection plus radiotherapy. The different radiotherapy doses and fractionation schedules did not altered survival.
PMCID: PMC1526744  PMID: 16808850

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