Linfoma de Hodgkin clássico na infância. Experiência de tratamento e fatores prognósticos / Classical Hodgkin?s lymphoma in childhood. Therapeutic experience and prognostic factors

Objetivos: Estimar as taxas de sobrevida global e livre de eventos em portadores de linfoma de Hodgkin (LH), bem como identificar fatores prognósticos. Métodos: Estudo de coorte retrospectivo, incluindo variáveis demográficas, laboratoriais, tipo histológico, estadiamento e tratamento de 107 pacientes menores de 18 anos de idade admitidos no Departamento de Pediatria do Centro de Tratamento e Pesquisa Hospital do Câncer, no período entre 1985 e 1995. Resultados: Dos pacientes, 81 (76%) eram do sexo masculino e 80% da raça branca. A média de idade foi 10 anos (2 a 18 anos). Adenomegalia cervical foi a principal queixa referida (68% dos pacientes) e 55% apresentavam tempo de queixa menor que seis meses. Os subtipos EN e CM foram encontrados em 43% e 41% dos casos, respectivamente. Os estádios clínicos II e III foram os mais frequentes (33% cada um). Os sítios metastáticos mais frequentes nos EC IV foram fígado (42%) e pulmão (38%). As taxas de SG e SLE em 10 anos foram de 82,4% e 82,5%, respectivamente. O estádio clínico se mostrou como fator prognóstico significativo para as SG e SLE. A análise univariada revelou a presença de sintomas B, nível de Hb £ 9,3 g/dl, leucócitos £ 6.100 mm3, plaquetas £ 274.000/mm3 e ocorrência de recaída como fatores de mau prognóstico, enquanto a análise múltipla mostrou como fatores prognósticos independentes a presença de sintomas B e contagem de plaquetas. Conclusões: A identificação de fatores prognósticos é valiosa para a adequada estratificação dos pacientes em grupos de risco, adequando-os a esquemas de tratamento que maximizem as taxas de cura e minimizem os efeitos colaterais tardios.

Conformal radiotherapy for lung cancer: interobservers' variability in the definition of gross tumor volume between radiologists and radiotherapists.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: There were no significant differences in the definition of gross tumor volume between radiologists and radiotherapists.

High-dose-rate brachytherapy for soft tissue sarcoma in children: a single institution experience.

PURPOSE: 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. RESULTS: 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%). CONCLUSION: 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.

The addition of ifosfamide/etoposide to cisplatin/teniposide improves the survival of children with retinoblastoma and orbital involvement.

This study aimed to determine the impact of the addition of ifosfamide/etoposide to a regimen containing cisplatin/teniposide on the survival of patients with retinoblastoma with orbital involvement. Thirty patients were treated at the A. C. Camargo Hospital, Brazil, from 1986 to 2002. From 1986 to April 1992 (period I, n=12), treatment consisted of 3 cycles of induction chemotherapy with cisplatin and teniposide, followed by maintenance with same drugs alternating with cyclophosphamide, vincristine, and doxorubicin every 21 days for 60 weeks. Since April 1992 (period II, n=18), the treatment consisted of 3 cycles of ifosfamide and etoposide followed by maintenance with same drugs, alternating with cisplatin and teniposide every 21 days for 36 weeks. In both periods, children were submitted to exenteration with eyelid preservation and orbital radiation therapy with 45 cGy, and also received intrathecal therapy with methotrexate plus dexamethasone and cytarabine. Kaplan-Meier method was used for survival analysis. The median age was 31 months. Most patients (86.7%) presented unilateral tumors. The 3-year overall survival was 34.4% and 72.2%, respectively, for patients treated during periods I and II (P=0.061). The addition of ifosfamide/etoposide to chemotherapy with cisplatin/teniposide improves survival in these patients, but further studies are still necessary.

Whole brain radiotherapy for brain metastases from breast cancer: estimation of survival using two stratification systems.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Salvage radiotherapy for biochemical relapse after complete PSA response following radical prostatectomy: outcome and prognostic factors for patients who have never received hormonal therapy.

OBJECTIVES: 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. RESULTS: 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. CONCLUSION: 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.

Preoperative external beam radiotherapy and reduced dose brachytherapy for carcinoma of the cervix: survival and pathological response.

PURPOSE: 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. RESULTS: 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. CONCLUSION: 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.

Intensity Modulated Radiotherapy (IMRT) in the postoperative treatment of an adenocarcinoma of the endometrium complicated by a pelvic kidney.

BACKGROUND: 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. CASE: 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. CONCLUSION: IMRT is a valid technique to prevent the kidney from radiation damage.

Chemotherapy followed by low dose radiotherapy in childhood Hodgkin's disease: retrospective analysis of results and prognostic factors.

PURPOSE: 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. RESULTS: 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. CONCLUSION: 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.

High-risk surgical stage 1 endometrial cancer: analysis of treatment outcome.

PURPOSE: 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. RESULTS: 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. CONCLUSION: 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.

Whole brain radiation therapy in management of brain metastasis: results and prognostic factors.

PURPOSE: 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. RESULTS: The OS in 1, 2 and 3 years was 25.1%, 10.4% and 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. CONCLUSION: 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.