Maria Aparecida Conte Maia

HIGH-DOSE-RATE BRACHYTHERAPY IN THE TREATMENT OF UTERINE CERVIX CANCER. ANALYSIS OF DOSE EFFECTIVENESS AND LATE COMPLICATIONS

PURPOSE This retrospective analysis aims to report results of patients with cervix cancer treated by external beam radiotherapy (EBR) and high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS From September 1992 to December 1996, 138 patients with FIGO Stages II and III and mean age of 56 years were treated. Median EBR to the whole pelvis was 45 Gy in 25 fractions. Parametrial boost was performed in 93% of patients, with a median dose of 14.4 Gy. Brachytherapy with HDR was performed during EBR or following its completion with a dose of 24 Gy in four weekly fractions of 6 Gy to point A. Median overall treatment time was of 60 days. Patient age, tumor stage, and overall treatment time were variables analyzed for survival and local control. Cumulative biologic effective dose (BED) at rectal and bladder reference points were correlated with late complications in these organs and dose of EBR at parametrium was correlated with small bowel complications. RESULTS Median follow-up time was 38 months. Overall survival, disease-free survival, and local control at 5 years was 53.7%, 52.7%, and 62%, respectively. By multivariate and univariate analysis, overall treatment time up to 50 days was the only statistically significant adverse variable for overall survival (p = 0.003) and actuarial local control (p = 0.008). The 5-year actuarial incidence of rectal, bladder, and small bowel late complications was 16%, 11%, and 14%, respectively. Patients treated with cumulative BED at rectum points above 110 Gy(3) and at bladder point above 125 Gy(3) had a higher but not statistically significant 5-year actuarial rate of complications at these organs (18% vs. 12%, p = 0.49 and 17% vs. 9%, p = 0.20, respectively). Patients who received parametrial doses larger than 59 Gy had a higher 5-year actuarial rate of complications in the small bowel; however, this was not statistically significant (19% vs. 10%, p = 0.260). CONCLUSION This series suggests that 45 Gy to the whole pelvis combined with four fractions of 6 Gy to point A with HDR brachytherapy is an effective and safe fractionation schedule in the treatment of Stages II and III cervix cancer if realized up to 50 days. To decrease the small bowel complications, we decreased the superior border of the parametrial fields to the S2-S3 level and the total dose to 54 Gy.

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.

Interstitial high-dose-rate brachytherapy combined with cervical dissection on head and neck cancer

The literature is scarce regarding the use of interstitial high‐dose‐rate brachytherapy (I‐HDR) as adjuvant treatment of the cervical region, and most reports are focused on primary tumors of the mobile tongue and oropharynx. We evaluated the outcome and morbidity related to an institutional treatment policy, using I‐HDR as the sole adjuvant treatment or in combination with external beam radiotherapy (EBRT) at the Departments of Radiation Oncology and Head and Neck Surgery, Hospital do Cancer, Sao Paulo, Brazil.

Reirradiation of the eye with plaque brachytherapy: A single institution experience report of eight consecutive patients submitted to retreatment after local relapse of malignant disease of the eye

PURPOSE To evaluate the feasibility of reirradiation of the eye with plaque brachytherapy (REPBT) for local recurrence (LR) of malignant disease of the eye as an alternative to enucleation or other local salvage treatments. METHODS AND MATERIALS It was performed a retrospective analysis of all patients who underwent REPBT for LR. The main parameters evaluated were local control and progression-free survival, besides the toxicity profile. RESULTS There were eight patients who underwent REPBT, seven due to uveal melanoma and one due to retinoblastoma. The median time between the first plaque brachytherapy and the salvage plaque brachytherapy was 24 months (8-49 months). After a median followup of 30 months (8-70 months), the actuarial 2-year local control and progression-free survival was 87.5% and 60%, respectively. All patients evolved with worsening of the visual acuity and cataract. Other complications observed were maculopathy (two patients) and glaucoma (one patient). CONCLUSIONS REPBT should be considered as an option for salvage therapy of LR of malignant disease of the eyes as it provides a high probability of tumor control and eye preservation without compromising disease-free survival.

Updated results of high-dose rate brachytherapy and external beam radiotherapy for locally and locally advanced prostate cancer using the RTOG-ASTRO phoenix definition

PURPOSE To evaluate the prognostic factors for patients with local or locally advanced prostate cancer treated with external beam radiotherapy (RT) and high dose rate brachytherapy (HDR) according to the RTOG-ASTRO Phoenix Consensus Conference. MATERIALS AND METHODS The charts of 209 patients treated between 1997 and 2005 with localized RT and HDR as a boost at the Department of Radiation Oncology, AC Camargo Hospital, Sao Paulo, Brazil were reviewed. Clinical and treatment parameters i.e.: patients age, Gleason score, clinical stage, initial PSA (iPSA), risk group (RG) for biochemical failure, doses of RT and HDR were evaluated. Median age and median follow-up time were 68 and 5.3 years, respectively. Median RT and HDR doses were 45 Gy and 20 Gy. RESULTS Disease specific survival (DSS) at 3.3 year was 94.2%. Regarding RG, for the LR (low risk), IR (intermediate risk) and HR (high risk), the DSS rates at 3.3 years were 91.5%, 90.2% and 88.5%, respectively. On univariate analysis prognostic factors related to DSS were RG (p=0.040), Gleason score <or= 6 ng/mL (p=0.002), total dose of HDR >or= 20 Gy (p<0.001) On multivariate analysis the only statistical significant predictive factor for biochemical control (bNED) was the RG, p<0.001 (CI-1.147-3.561). CONCLUSIONS Although the radiation dose administered to the prostate is an important factor related to bNED, this could not be established with statistical significance in this group of patients. To date, in our own experience, HDR associated to RT could be considered a successful approach in the treatment of prostate cancer.

Prognostic value of nuclear factor κ B expression in patients with advanced cervical cancer undergoing radiation therapy followed by hysterectomy.

Aims The nuclear factor κ B (NF-κB) family comprises transcription factors that promote the development and progression of cancer. The NF-κB pathway is induced by radiation therapy and may be related to tumour radioresistance. The aim of this study was to evaluate the expression of NF-κB as a predictor of the response to radiotherapy and its value as a prognostic marker. Methods A retrospective analysis was performed in a series of 32 individuals with stage IB2 and IIB cervical cancer who underwent radiotherapy, followed by radical hysterectomy, from January 1992 to June 2001. NF-κB-p65 and NF-κB-p50 expression was examined by immunohistochemistry in biopsies from all patients before radiotherapy and in 12 patients with residual tumours after radiotherapy. Results 16 (50%) patients had residual disease after radical hysterectomy. The median follow-up time was 73.5 months, and the 5-year overall survival was 66.5%. Before radiotherapy, cytoplasmic expression of NF-κB-p65 and NF-κB-p50 was noted in 91% and 97% of cases, respectively, versus 59% of cases with nuclear expression of these subunits. Cytoplasmic expression of NF-κB-p65 and NF-κB-p50 in the residual tumours after radiotherapy was observed in 50% of cases; 75% of cases with residual tumours had nuclear expression of NF-κB-p50 versus none with NF-κB-p65. NF-κB-p65 and NF-κB-p50 did not correlate with the risk of residual tumours after radiotherapy or recurrence or death. Conclusions These data suggest that NF-κB does not predict the response to radiotherapy and does not correlate with poor outcomes in advanced cervical cancer.

Hemangioma vertebral sintomático tratado com radioterapia exclusiva: relato de caso e revisão da literatura

We report the clinical and imaging findings of a patient with a symptomatic vertebral hemangioma treated with radiotherapy alone. There was partial relief of the pain 3 months after radiotherapy. We recommend a total dose of 40 Gy at 2 Gy per fraction. A review of literature is also presented.

Radioterapia adjuvante no tratamento do câncer de endométrio: experiência com a associação de radio-terapia externa e braquiterapia de alta taxa de dose

OBJECTIVE: To review the results of adjuvant external beam radiation therapy (EBRT) combined with high-dose rate brachytherapy (HDR-BT) for the treatment of endometrial carcinoma. MATERIALS AND METHODS: We retrospectively evaluated 141 patients treated with EBRT and HDR-BT after surgery between January 1993 and January 2001. EBRT was performed with a median dose of 45 Gy, and HDR-BT was performed with a median dose of 24 Gy, with four weekly insertions of 6 Gy. The median age of the patients was 63 years and the disease stage distribution was: CS I (FIGO), 52.4%; CS II, 13.5%; CS III, 29.8%; CS IV, 4.3%. RESULTS: With a median follow-up of 53.7 months, the disease free survival (DFS) at five years was: CS I, 88.0%; CS II, 70.8%; CS III, 55.1%; CS IV, 50.0% (p = 0.0003). Global survival after five years was: CS I, 79.6%; CS II, 74.0%; CS III, 53.6%; CS IV, 100.0% (p = 0.0062). Factors affecting the DFS were histological grade and serous-papillary histology. Recurrence of the disease was observed in 33 cases, 13 (9.2%) of these occurred in the pelvis, vagina or vaginal vault. EBRT + HDR-BT of the vaginal vault allowed disease control in 90.8% of the cases. CONCLUSION: Radiation therapy is essential for loco-regional control of endometrial cancer and can achieve excellent cure rates in the initial stages. In more advanced stages, therapeutic failure frequently appears as distant metastases suggesting the need for complementary systemic therapy using new treatment modalities, particularly chemotherapy.

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

PURPOSE: To evaluate the influence on local control in adult patients with soft tissue sarcomas of the limbs that underwent limb-sparing surgery and high-dose rate brachytherapy (HDRB) in association with teletherapy. MATERIAL AND METHODS: Sixteen patients treated from 1993 to 1999 were reviewed. Teletherapy was used pre- or postoperatively (30¾55 Gy) in association with HDRB in a dose range of 18¾36 Gy (fx 3¾6 Gy BID). The linear quadratic model was used to calculate the biological effective dose (BED) and the values obtained were compared with data from the literature, of studies that employed teletherapy and low-dose rate brachytherapy (LDRB). RESULTS: Soft tissue sarcomas BED mean and median values were 78.5 Gy7 and 80 Gy7, respectively. Univariated analysis showed that BED for patients with soft tissue sarcoma of the limbs submitted to HDRB was similar to the value of 83 Gy7 of patients submitted to LDRB (p = 0.008). Actuarial local control, disease free and overall survival rates at 5-years were 83.2%, 75% and 93.7%, respectively. CONCLUSIONS: HDRB appears to be an effective complementary method to teletherapy in the treatment of soft tissue sarcomas. The local control rates are comparable to those reported in the literature. However, studies with longer follow-up and a larger number of patients are still necessary in order to determine the true potential of HDRB as a substitute for LDBR.