Intraoperative radiotherapy for brain metastases: first-stage results of a single-arm, open-label, phase 2 trial.

OBJECTIVE: Focal stereotactic radiosurgery to the surgical cavity lowers local recurrence after resection of brain metastases (BM). To evaluate local control (LC) and brain disease control (BDC) after intraoperative radiotherapy (IORT) for resected BM. METHODS: Adult patients with completely resected single supratentorial BM were recruited and underwent IORT to the cavity with a prescribed dose of 18 Gy to 1 mm-depth. Primary endpoints were actuarial LC and BDC. Local failure (LF) and distant brain failure (DBF), with death as a competing risk, were estimated. Secondary endpoints were overall survival (OS) and incidence of radiation necrosis (RN). Simon's two-stage design was used and estimated an accrual of 10 patients for the first-stage analysis and a LC higher than 63% to proceed to second stage. We report the final analysis of the first stage. RESULTS: Between June 2019 to November 2020, 10 patients were accrued. Median clinical and imaging FU was 11.2 and 9.7 months, respectively. Median LC was not reached and median BDC was 5 months. The 6-month and 12-month LC was 87.5%. The 6-month and 12-month BDC was 39% and 13%, respectively. Incidence of LF at 6 and 12 months was 10% and of DBF at 6 and 12 months was 50% and 70%, respectively. Median OS was not reached. The 6-month and 12-month OS was 80%. One patient had asymptomatic RN. CONCLUSION: IORT for completely resected BM is associated with a potential high local control and low risk of RN, reaching the pre-specified criteria to proceed to second stage and warranting further studies.

Intraoperative breast radiotherapy: survival, local control and risk factors for recurrence.

BACKGROUND: Whole breast irradiation reduces loco-regional recurrence and risk of death in patients submitted to breast-conserving treatment. Data show that radiation to the index quadrant alone may be enough in selected patients. AIM: To report the experience with intra-operative radiotherapy (IORT) with Electron-beam Cone in Linear Accelerator (ELIOT) and the results in overall survival, local control and late toxicity of patients submitted to this treatment. MATERIALS AND METHODS: 147 patients treated with a median follow up of 6.9 years (0.1â¿¿11.5 years). The actuarial local control and overall survival probabilities were estimated using the Kaplan Meier method. All tests were two-sided and p â¿¤ 0.05 was considered statistically significant. RESULTS: Overall survival of the cohort in 5 years, in the median follow up and in 10 years was of 98.3%, 95.1% and 95.1%, respectively, whereas local control in 5 years, in the median follow up and in 10 years was of 96%, 94.9% and 89.5%, respectively. Two risk groups were identified for local recurrence depending on the estrogen or progesterone receptors, axillary or margin status and lymphovascular invasion (LVI) (p = 0.016). CONCLUSIONS: IORT is a safe and effective treatment. Rigorous selection is important to achieve excellent local control results.

Heterogeneity of HER2 Expression in Circulating Tumor Cells of Patients with Breast Cancer Brain Metastases and Impact on Brain Disease Control.

HER2 expression switching in circulating tumor cells (CTC) in breast cancer is dynamic and may have prognostic and predictive clinical implications. In this study, we evaluated the association between the expression of HER2 in the CTC of patients with breast cancer brain metastases (BCBM) and brain disease control. An exploratory analysis of a prospective assessment of CTC before (CTC1) and after (CTC2) stereotactic radiotherapy/radiosurgery (SRT) for BCBM in 39 women was performed. Distant brain failure-free survival (DBFFS), the primary endpoint, and overall survival (OS) were estimated. After a median follow-up of 16.6 months, there were 15 patients with distant brain failure and 16 deaths. The median DBFFS and OS were 15.3 and 19.5 months, respectively. The median DBFFS was 10 months in patients without HER2 expressed in CTC and was not reached in patients with HER2 in CTC (p = 0.012). The median OS was 17 months in patients without HER2 in CTC and was not reached in patients with HER2 in CTC (p = 0.104). On the multivariate analysis, DBFFS was superior in patients who were primary immunophenotype (PIP) HER2-positive (HR 0.128, 95% CI 0.025-0.534; p = 0.013). The expression of HER2 in CTC was associated with a longer DBFFS, and the switching of HER2 expression between the PIP and CTC may have an impact on prognosis and treatment selection for BCBM.

Postmastectomy Radiation Therapy Bolus Associated Complications in Patients Who Underwent 2-stage Breast Reconstruction.

Purpose: This study aimed to evaluate the association of bolus and 2-stage breast reconstruction complications, and whether the dosimetric advantage translates into improvements in local control. Methods and Materials: We retrospectively analyzed data from 2008 to 2019 of women who underwent a mastectomy and a planned 2-stage breast reconstruction, followed by adjuvant radiation therapy. We reviewed all data from medical records and radiation plans regarding patient characteristics, diagnoses, surgeries, complications, pathology, staging, systemic therapy, radiation therapy, and outcomes, and compared complication rates according to bolus usage. Results: A total of 288 women, age 25 to 71 years, were included in the study. Of these women, 6 were treated with daily bolus and 19 with alternate days bolus, totaling 25 of 288 patients (8.7%) in the bolus group. A total of 226 patients (78.5%) had the second stage performed. The median follow-up time was 61 months. The rates for 5-year overall survival and locoregional control were both 97%, and the metastasis-free rate was 83%. In the first stage, 6.25% of patients in the entire cohort had an infection and 4.2% had implant loss. Daily bolus significantly increased the risk of expander infection (hazard ratio [HR]: 10.3; 95% confidence interval [CI], 1.7-61.8) and loss (HR: 13.89; 95% CI, 2.24-85.98), but alternate-day bolus showed a nonsignificant increase for expander infection (HR: 1.14; 95% CI, 0.14-9.295) and loss (HR: 1.5; 95% CI, 0.19-12.87). Bolus was not associated with second-stage complications or local-regional failure. Local infection and implant loss were more frequent in the second than in the first stage (5.2% vs 10.2% and 4.2% vs 12.8%, respectively). Conclusions: Skin bolus significantly increased first-stage breast reconstruction complications (infection and reconstruction failure). Despite the small sample size and the need for future studies, these findings need to be taken into consideration when planning treatment and reconstruction, and recommendations should be individualized.

Radiation therapy with elective lymph node irradiation for breast cancer: dosimetric study and impact on cardiovascular risk and second neoplasms.

OBJECTIVE: The aim of this study was to perform dosimetric analysis of radiotherapy (RT) plans with or without elective nodal irradiation (ENI) and estimate whether the increase in mean doses (MDs) in the heart and lungs with ENI may lead to late side effects that may surpass the benefits of treatment. METHODS: The dosimetric analysis of 30 treatment plans was done with or without ENI. The planning and dose-volume histograms were analyzed, and the impact on the mortality of cardiovascular and lung cancer was estimated based on the correlation of the dosimetric data with data from population studies. RESULTS: RT with ENI increased the doses in the lungs and heterogeneity in the plans compared to breast-exclusive RT. When the increase in MDs is correlated with the increase of late side-effect risks, the most important effect of ENI is the increased risk of lung cancer, especially in patients who smoke (average increase in absolute risk=1.38%). The increase in the absolute risk of cardiovascular diseases was below 0.1% in the all the situations analyzed. CONCLUSIONS: ENI increases the heterogeneity and the doses at the lungs. When recommending ENI, the risks and benefits must be taken into account, considering the oncology factors and the plan of each patient. Special attention must be given to patients who smoke as ENI may lead to a significant increase in MD in the lung and the increased risk of radiation-induced lung cancer may surpass the benefits from this treatment.

Prospective Assessment of the Association Between Circulating Tumor Cells and Control of Brain Disease After Focal Radiation Therapy of Breast Cancer Brain Metastases.

PURPOSE: Predicting the risk of early distant brain failure (DBF) is in demand for management decisions in patients who are candidates for local treatment of brain metastases. This study aimed to analyze the association between circulating tumor cells (CTCs) and brain disease control after stereotactic radiation therapy/radiosurgery (SRT) for breast cancer brain metastasis (BCBM). METHODS AND MATERIALS: We prospectively assessed CTCs before (CTC1) and 4 to 5 weeks after (CTC2) SRT and their relationship with the number of new lesions (NL) suggestive of BCBM before SRT. CTC were quantified and analyzed by immunocytochemistry to evaluate the expression of the proteins COX2, EGFR, ST6GALNAC5, NOTCH1, and HER2. Distant brain failure-free survival (DBFFS), the primary endpoint, diffuse DBFFS (D-DBFFS), and overall survival were estimated. Analysis for DBF within 6 months, with death as competing risk, was performed. RESULTS: Patients were included between 2016 and 2018. CTCs were detected in all 39 patients before and in 34 of 35 patients after SRT. After median follow-up of 16.6 months, median DBFFS, D-DBFFS, and overall survival were 15.3, 14.1, and 19.5 months, respectively. DBF at 6 months was 40% with CTC1 ≤0.5 and 8.82% with CTC1 >0.5 CTC/mL (P = .007), and D-DBF at 6 months was 40% with CTC1 ≤0.5 and 0 with CTC1 >0.5 CTC/mL (P = .005) and 25% with NL/CTC1 >6.8 and 2.65% with NL/CTC1 ≤6.8 (P = .063). On multivariate analysis, DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 8.27; 95% confidence interval, 2.12-32.3; P = .002), and D-DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 10.22; 95% confidence interval, 1.99-52.41; P = .005). Protein expression was not associated with outcomes. CONCLUSIONS: These data suggest that CTC1 and NL/CTC1 may have a role as a biomarker of early diffuse DBF and as a subsequent guide between focal or whole-brain radiation therapy in patients with BCBM.

Intraoperative radiation therapy for the treatment of recurrent retroperitoneal and pelvic tumors: a single-institution analysis.

BACKGROUND: Patients with recurrent retroperitoneal and pelvic region tumors often require multimodal therapies. Intraoperative radiation therapy (IORT) can deliver high-dose radiation to tumor beds, even if first-line external beam radiation therapy (EBRT) was administered. We evaluated local control (LC) and survival in patients receiving IORT for recurrent tumors. METHODS: We retrospectively analyzed 41 patients with isolated pelvic or retroperitoneal recurrences of colorectal, gynecological, or retroperitoneal primary tumors. Following salvage surgery, all patients underwent tumor bed IORT via electron beam or high dose rate brachytherapy. Isolated IORT (median dose: 15 Gy) was administered to patients who had received first-line EBRT; other patients received IORT (median dose 12 Gy) plus EBRT. Local (LF), regional (RF), and distant failures (DF) were evaluated, and the Kaplan-Meier method and log-rank test were used to evaluate and compare overall survival (OS) from the date of IORT. RESULTS: Forty-one patients underwent 44 treatments, including 27 (61.3%) isolated IORT and 17 (38.7%) IORT and EBRT combination regimens. The median follow-up was 8.1 years (range: 4.4-11.7 years), and the 2, 5, and 8 year overall LC rates were 87.9, 64.0, and 49.8%, respectively. Regarding resection status, the respective 2, 5, and 8 year LC rates were 90, 76, and 76% for R0 resection and 75, 25, and 0% for R1 resection (p < 0.001). The 2, 5, and 8 year OS rates were 68, 43, and 26%, respectively. OS was better among patients with LC (p < 0.001). Twenty-four patients (58.5%) experienced a DF, and the 5 year OS rates for the patients with and without DF were 36 and 52%, respectively (p = 0.04). In a multivariate analysis, LF (p = 0,012) and recurrent retroperitoneal sarcoma (p = 0,014) were identified as significant predictors of worse OS. Thirteen patients (31%) developed clinically treatable complications related to IORT. CONCLUSIONS: Many patients achieve long-term OS and LC without significant morbidity after salvage surgery and IORT, especially in case of clear margins.

Radiation therapy with elective lymph node irradiation for breast cancer: dosimetric study and impact on cardiovascular risk and second neoplasms

SUMMARY OBJECTIVE: The aim of this study was to perform dosimetric analysis of radiotherapy (RT) plans with or without elective nodal irradiation (ENI) and estimate whether the increase in mean doses (MDs) in the heart and lungs with ENI may lead to late side effects that may surpass the benefits of treatment. METHODS: The dosimetric analysis of 30 treatment plans was done with or without ENI. The planning and dose-volume histograms were analyzed, and the impact on the mortality of cardiovascular and lung cancer was estimated based on the correlation of the dosimetric data with data from population studies. RESULTS: RT with ENI increased the doses in the lungs and heterogeneity in the plans compared to breast-exclusive RT. When the increase in MDs is correlated with the increase of late side-effect risks, the most important effect of ENI is the increased risk of lung cancer, especially in patients who smoke (average increase in absolute risk=1.38%). The increase in the absolute risk of cardiovascular diseases was below 0.1% in the all the situations analyzed. CONCLUSIONS: ENI increases the heterogeneity and the doses at the lungs. When recommending ENI, the risks and benefits must be taken into account, considering the oncology factors and the plan of each patient. Special attention must be given to patients who smoke as ENI may lead to a significant increase in MD in the lung and the increased risk of radiation-induced lung cancer may surpass the benefits from this treatment.

Local control after radiosurgery for brain metastases: predictive factors and implications for clinical decision.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Results of high dose rate afterloading brachytherapy boost to conventional external beam radiation therapy for initial and locally advanced prostate cancer.

PURPOSE: To evaluate the impact on biochemical control (bNED), acute and late gastro-intestinal (GI) and urological (GU) morbidity of initial and locally advanced prostate cancer treated with fractionated transrectal ultrasound-guided (TRUS) high dose rate after loading brachytherapy (HDR-B) as a boost to conventional external beam radiation therapy (EBRT). PATIENTS AND METHODS: From March 1997 to February 2000 a total of 119 patients with any of the following characteristics were eligible for study entry: biopsy proven adenocarcinoma Gleason scored (GS), initial prostatic specific antigen (PSA) level dosage 1992 AJCC clinical stage T3a or less, and prostatic volume <60 cc. All patients had prior to HDR-B a course of EBRT 6 MV photons to a median dose of 45 Gy, in 1.8 Gy fractions, to the prostate and seminal vesicles only. HDR-B treatment planning and dosimetric calculations were generated with the Nucletron Planning System. Patients were grouped into two groups, according to their risk for biochemical failure: low-risk group without (LR) or with neoadjuvant total androgen deprivation (AD) prior to EBRT (LR+AD) and high-risk group without (HR) or with neoadjuvant AD (HR+AD), for bNED and dose-escalation protocol. LR encompassed patients who presented GS<6, T1 or T2a and or initial PSA<10 ng/ml, who were treated with 16 Gy (4 Gy fractions, b.i.d.) HDR-B. The remaining patients were grouped into HR or HR+AD and received 20 Gy (5 Gy fractions, b.i.d.) HDR-B. The planning was optimized using the standard geometric optimization. Biological effective doses (BED) for tumor control and late responding tissue were calculated using a alpha/beta ratio of 1.5 and 3 Gy, respectively. They were matched with bNED, acute and late gastrointestinal (GI) and urological (GU) morbidity, according to the RTOG/EORTC scoring criteria. RESULTS: Median age of patients was 68 years (range 47-83), with a median follow-up of 41 months (range 18-48). The crude and actuarial biochemical controls (bNED) in 48 months for all patients were 69.5 and 75.3%, respectively. When grouped into LR, LR+AD, HR and HR+AD the actuarial bNED were 78.2, 76, 76 and 72.3% (P=0.89), respectively. Acute GU and GI morbidity G1-2 were seen in 18.5% (20/108) and 10.2% (11/108) of patients with spontaneous regression. Late GI and GU morbidity G1-2 were seen in 12% (13/108) and 4.6 (5/108) of patients, with no need of intervention. No acute or late G3-4 GU or GI morbidity was seen. CONCLUSIONS: There are many advantages in HDR-B, but the most important ones are the capability of on-line dosimetry, quality control and the procedure being very conformal. There is a low incidence of GU and GI acute and late morbidity with acceptable bNED when treating initial and locally advanced prostate cancer with HDR-B as a boost to EBRT, but we still need to wait for results of phase III open trials that analyze HDR-B and conformal therapy.

Tumor control, eye preservation, and visual outcomes of ruthenium plaque brachytherapy for choroidal melanoma.

PURPOSE: To evaluate outcomes in patients with posterior choroidal melanoma treated with ruthenium ((106)Ru) brachytherapy. METHODS AND MATERIALS: A retrospective single institutional analysis of 83 of 94 consecutive patients who underwent (106)Ru brachytherapy was performed. Disease was mainly staged as small- and medium-sized nonmetastatic melanoma. The main parameters evaluated were tumor control (local control [LC] and progression-free survival [PFS]) and ocular preservation (enucleation-free survival [EFS]). Besides, functional evaluation was performed and complications were described. RESULTS: The median follow-up was 39 (6-83) months. The median values of height and maximal basal diameter were 4.3 and 9.3mm, respectively. Median apical and basal doses were 100 and 307Gy, respectively. The actuarial 2-year LC, PFS, and EFS were 96.2%, 96.2%, and 95.5%, respectively. Actuarial 5-year LC, PFS, and EFS were 93.6%, 93.6%, and 84.1%, respectively. Preinsertion visual acuity (VA) maintenance was 34% (equal or better than before treatment). Approximately 56% of patients stayed with a minimum functional VA of 0.1 or more, from whom more than half stayed with 0.5 or more. Cataract was seen in 16% of treated eyes, and glaucoma was the rarest complication, with an incidence of 3%. CONCLUSIONS: Small- and medium-sized choroidal melanomas can be adequately treated with (106)Ru brachytherapy, with high rates of tumor control and ocular preservation. Moreover, acceptable incidence of complications such as glaucoma and cataract are seen, and a reasonable part of patients stay with a minimum functional VA.

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.

UNLABELLED: 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.

Radiotherapy and collagenosis: is it safe? A case report of reirradiation in a patient with scleroderma

Historically, scleroderma and other collagenous diseases have been considered a relative contraindication to radiation. The literature has few studies describing poor outcomes and cosmesis in this situation and there are almost no data concerning about reirradiation and colagenosis. The authors describe a case of a patient with a soft tissue sarcoma in the arm submitted to conservative surgery. They describe the outcome, cosmesis and function of this rare twice-irradiated scleroderma patient.

High-dose-rate brachytherapy as part of a multidisciplinary treatment of nasopharyngeal lymphoepithelioma in childhood.

BACKGROUND: Nasopharyngeal carcinoma in childhood is rare. Radiochemotherapy is considered the standard treatment and yields increased survival and local control rates. In this article, the authors report on the results from the multidisciplinary treatment of pediatric patients who had nasopharyngeal lymphoepithelioma with radiochemotherapy, including high-dose-rate brachytherapy of the primary tumor site. METHODS: Between May 1992 and May 2000, 16 children with nasopharyngeal lymphoepithelioma received neoadjuvant chemotherapy, conventional external beam radiotherapy, high-dose-rate brachytherapy, and adjuvant chemotherapy. Patients ranged in age from 7 years to 18 years, and 9 patients were male. Patient distribution according to clinical disease stage was as follows: Stage III, 1 patient; Stage IVA, 5 patients; Stage IVB, 9 patients; and Stage IVC, 1 patient. Three cycles of neoadjuvant and adjuvant chemotherapy in 3-week intervals were administered with cyclophosphamide, vincristine, doxorubicin, and cisplatin. The median doses of external beam radiotherapy to the primary tumor, positive lymph nodes, and subclinical areas of disease were 55 grays (Gy), 55 Gy, and 45 Gy, respectively. Children received 2 insertions of high-dose-rate brachytherapy at 5 Gy per insertion: These were performed with metallic applicators inserted through the transnasal access under local anesthesia. RESULTS: The median of follow-up was 54 months. At the time of last follow-up, 13 patients were alive without disease, 2 patients had died of disease, and 1 patient had died of treatment-related cardiac failure. Local control was achieved in 15 of 16 patients. Chemotherapy-related and radiotherapy-related acute toxicity was relevant but tolerable. CONCLUSIONS: In the current study, it was shown that the treatment was effective in the control of both local and distant disease, although there was relevant acute and late toxicity. High-dose-rate brachytherapy was deliverable on an outpatient basis with local anesthesia. Close follow-up of these patients was necessary to evaluate the significance of treatment-related late effects and their impact on quality of life.

Tratamento conservador do câncer de mama T2 (≥ 4 cm) e T3 por quimioterapia neoadjuvante, quadrantectomia, braquiterapia com alta taxa de dose como reforço de dose, teleterapia complementar e quimioterapia adjuvante: análise de controle local e sobrevida global / Breast conserving treatment of breast carcinoma T2 (≥ 4 cm) and T3 by neoadjuvant chemotherapy, quadrantectomy, high dose rate brachytherapy as a boost, external beam radiotherapy and adjuvant chemotherapy: local control and overall survival analysis

OBJETIVO: Avaliar o tratamento de carcinomas de mama T2 (≥ 4 cm) e T3, por quimioterapia neoadjuvante, quadrantectomia e braquiterapia com alta taxa de dose como reforço de dose (boost), radioterapia complementar e quimioterapia adjuvante, quanto ao controle local e sobrevida global.MATERIAL E MÉTODO: Trata-se de estudo clínico prospectivo descritivo que avaliou 88 pacientes com idade entre 30 e 70 anos, portadoras de carcinoma ductal infiltrante, nos estádio clínico IIb e IIIa, responsivas à quimioterapia neoadjuvante, tratadas entre junho de 1995 e dezembro de 2006. A resposta do tumor foi avaliada por método clínico antes e após três ou quatro ciclos de quimioterapia contendo antracíclicos. O seguimento mediano foi de 58 meses. Sobrevida global e controle local foram analisados segundo o método de Kaplan-Meier. RESULTADOS: O controle local e a sobrevida global em cinco anos foram de 90% e 73,5%, respectivamente. CONCLUSÃO: O controle local e a sobrevida global são comparáveis aos observados em outras formas terapêuticas.

OBJECTIVE: To assess the treatment of breast cancer T2 (≥ 4 cm) and T3 through neoadjuvant chemotherapy, quadrantectomy and high dose rate brachyterapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering local control and overall survival. MATERIAL AND METHOD: This clinical prospectivedescriptive study was based on the evaluation of 88 patients rangingfrom 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIb and IIIa, responsive to the neoadjuvant chemotherapy, treated from June/1995 to December/2006. Median follow-up was 58 months. Using clinical methods the tumor was evaluated before and after three or four cycles of chemotherapy based on antraciclins. Overall survival and local control were assessed according to Kaplan-Meier methodology. RESULTS: Local control and overall survival in five years were 90% and 73.5%, respectively. CONCLUSION: Local control and overall survival were comparable to other forms of treatment.

Impacto da adição da temozolamida à radioterapia no tratamento de crianças portadoras de tumor de tronco cerebral / Impact of the addition of temozolomide to radiotherapy in the treatment of children with brain stem tumors

OBJETIVO: Analisar o impacto da adição da temozolamida à radioterapia em tumores de tronco cerebral em crianças. MATERIAL E MÉTODO: Entre 2000 e 2005 foram analisadas, retrospectivamente, 64 crianças com tumor do tronco cerebral. Dessas crianças, 32 receberam temozolamida(grupo 1) e 32 não a receberam (grupo 2). RESULTADOS: A idade mediana no grupo 1 foi de 8,2 anos e no grupo 2 foi de 7,5 anos. A localização tumoral era predominantemente difusa (53%) emambos os grupos. Todos os pacientes receberam radioterapia com doses superiores a 50 Gy. No grupo1 foram ministrados nove ciclos, em média, de quimioterapia (3û14 ciclos). O tempo de progressão de doença foi de 7,9 meses no grupo 2 versus 13,8 meses no grupo 1. A sobrevida global foi de 8,8 meses (0,3û30,9 meses) no grupo 1 e de 14,6 meses (4,3û33 meses) no grupo 2. CONCLUSÃO: A utilização da temozolamida após a radioterapia proporcionou aumento da sobrevida, deseis meses em média, nos pacientes pediátricos com tumor do tronco cerebral.

OBJECTIVE: To analyze the impact of adding temozolomide to radiotherapyin pediatric brain stem tumors. MATERIAL AND METHOD: Between 2000 and 2005, 64 children with brain stem tumor were analyzed: 32 received temozolomide (group 1) and 32 did not(group 2). RESULTS: The median age of patients in group 1 was 8.2 year-old and in group 2 was 7.5 year-old. The predominant tumoral localization was diffuse (53%) in both groups. All of the patients were submitted to radiotherapy. In group 1, the median number of temozolomide cycles was 9 (3û14 cycles). Time of disease progression was 7.9 months in group 2 versus 13.8 months in group 1. Overall survival was 8.8 months (0.3û30.9 months) in group 1 and 14.6 months (4.3û33 months) in group 2. CONCLUSION: In our institution,adding temozolomide to radiotherapy increased the overall survival in approximately six months in brain stem pediatric tumors.

Biochemical Relapse for Prostate Cancer Following Radical Prostatectomy: Salvage Radiotherapy Without HormonalTherapy

Objectives: This paper aims to study biochemical control, hormonal therapy-free survival, and prognostic factors related tosalvage radiation for prostate cancer patients submitted to radical prostatectomy (RP) without hormonal therapy (HT) before orduring radiation. Materials and Methods: from August 2002 to July 2004, 39 prostate cancer patients submitted to RPpresented biochemical failure after achieving PSA nadir (<0.2ng/ml). All patients were submitted to three-dimensional conformalexternal beam radiation therapy (3DC-EBRT) and no patients had received HT. Median age was 62 years, median preoperativePSA was 9.4ng/ml, median Gleason Score was 7. We defined PSA rise above 0.2 as biochemical failure after surgery. Median3DC-EBRT dose was 70Gy, and biochemical failure after EBRT was defined as three consecutive rises in PSA or a single risesufficient to trigger HT. Results: Biochemical non-evidence of disease (BNED) in 3 years was 72%. PSA doubling time (PSADT)lower than 4 months (p=0.04), and delay to salvage EBRT (p=0.05) were associated to worse chance of successful salvagetherapy. Late morbidity was acceptable. Conclusion: Expressive PSA control (72% BNED / 3years) could be achieved withsalvage radiotherapy in well-selected patients. The importance of PSADT was confirmed, and radiotherapy should be started asearly as possible. Follow-up is somewhat short, but it is possible to conclude that it is possible to achieve a long interval freefrom hormonal therapy with low rate of toxicity, avoiding or at least delaying morbidity related to hormonal treatment.radiotherapy

Conventional External Beam Radiation Therapy and High Dose Rate Afterloading Brachytherapy as a Boost for Patients Olderthan 70 years

The treatment options for patients with non metastatic prostate cancer range from observation, radical prostatectomy, radiationtherapy, hormonal therapy to various combination of some to all of them. Objective: We evaluated the impact on biochemicalcontrol of disease (bNED), acute and late intestinal (GI) and urological (GU) morbidity for a group of patients older than 70years presenting initial or locally advanced prostate cancer treated with fractionated high dose rate brachytherapy (HDRB) asa boost to conventional external beam radiation therapy (RT) at the Department of Radiation Oncology from Hospital do CâncerA. C. Camargo, São Paulo, Brazil. Methods: A total of 56 patients older than 70 were treated from March, 1997 to June,2002. All patients had prior to HDRB a course of RT to a median dose of 45 Gy. HDRB doses ranged from 16 Gy to 20 Gy, givenin 4 fractions. Results: The median age of the patients was 74.4 years (range 70-83) and the median follow-up 33 months(range 24 to 60). The 5-year actuarial bNED rate was 77%. Acute GU and GI morbidity G1-2 were seen in 17.8% and 7.1% ofpatients, respectively. Late G1 or G2 GU morbidity was seen in 10.7% of the patients, while late G3 morbidity was observedin 7.1% of the patients, represented by urethral strictures. Conclusion: this group of patients had similar bNED rates whencompared to literature, with acceptable morbidity rates.

Radioterapia adjuvante no tratamento do câncer de endométrio: experiência com a associação de radio-terapia externa e braquiterapia de alta taxa de dose / Adjuvant radiation therapy for the treatment of endometrial cancer: experience with combination of external radiation therapy and high-dose rate brachytherapy

OBJETIVO: Analisar, retrospectivamente, os resultados da radioterapia externa (RT) combinada a braquiterapia de alta taxa de dose (BATD), adjuvantes à cirurgia para o carcinoma de endométrio. MATERIAIS E MÉTODOS: Avaliamos 141 pacientes tratados com RT e BATD adjuvantes à cirurgia, no período de janeiro de 1993 a janeiro de 2001. RT pélvica foi realizada com dose mediana de 45 Gy, e BATD realizada na dose mediana de 24 Gy, em quatro inserções semanais de 6 Gy. A idade mediana das pacientes foi de 63 anos e a distribuição por estádio clínico (EC) foi: EC I (FIGO), 52,4 por cento; EC II, 13,5 por cento; EC III, 29,8 por cento; EC IV, 4,3 por cento. RESULTADOS: Com seguimento mediano de 53,7 meses, a sobrevida livre de doença (SLD) em cinco anos foi: EC I, 88,0 por cento; EC II, 70,8 por cento; EC III, 55,1 por cento; EC IV, 50,0 por cento (p = 0,0003). A sobrevida global em cinco anos foi: EC I, 79,6 por cento; EC II, 74,0 por cento; EC III, 53,6 por cento; EC IV, 100,0 por cento (p = 0,0062). Fatores que influíram na SLD foram grau histológico e histologia seropapilífera. Dos 33 casos que apresentaram recidiva da doença, em 13 (9,2 por cento) esta ocorreu na pelve, vagina ou cúpula vaginal. RT + BATD do fundo vaginal permitiram o controle da doença em 90,8 por cento dos casos. CONCLUSÃO: A RT exerce papel fundamental no controle loco-regional do câncer de endométrio e permite excelentes taxas de cura nos estádios iniciais. Para os estádios mais avançados, a falha terapêutica tende a ser a distância, sugerindo a necessidade de complementação terapêutica sistêmica, com introdução de novas modalidades de tratamento, em particular a quimioterapia.

Cirurgia conservadora, radioterapia externa e reforço de dose com braquiterapia de alta taxa de dose: uma nova perspectiva no tratamento de sarcomas de partes moles do adulto / Limb-sparing surgery, external beam radiotherapy and boost with high-dose rate brachytherapy: a new perspective for the treatment of soft tissue sarcomas in adults

OBJETIVO: Avaliar a influência no controle local de pacientes adultos e portadores de sarcoma de partes moles em extremidades e submetidos a cirurgia conservadora do membro, com braquiterapia de alta taxa de dose (BATD) como reforço para a radioterapia externa (RT). MATERIAL E M+TODOS: Foram avaliados 16 pacientes tratados, de 1993 até 1999. A RT foi utilizada com finalidade pré ou pós-operatória (30-55 Gy) e BATD com dose de 18-36 Gy (fx 3-6 Gy BID). Com base no modelo linear quadrático calculou-se a dose efetiva biológica ("biological effective dose" - BED) para o tumor e comparou-se seu valor a dados da literatura internacional, que utiliza tratamentos com RT e braquiterapia de baixa taxa de dose (BBTD). RESULTADOS: Os valores médios e medianos da BED para os sarcomas de partes moles foram de 78,5 Gy7 e 80 Gy7. A análise univariada mostrou que a BED para o tumor, quando utilizada BATD, era semelhante ao valor de 83 Gy7 quando utilizada BBTD (p = 0,008). As taxas de controle local, sobrevida livre de doença e sobrevida global atuarial em cinco anos foram de 83,2 por cento, 75 por cento e 93,7 por cento, respectivamente. CONCLUSiES: A BATD, quando utilizada como método complementar no reforço de dose da RT no tratamento conservador dos sarcomas de partes moles, apresenta taxas de controle local equiparáveis às da literatura internacional; no entanto, estudos com número maior de pacientes e período maior de seguimento são ainda necessários para determinar o verdadeiro potencial da BATD em substituir a BBTD.