Ototoxicity evaluation in medulloblastoma patients treated with involved field boost using intensity-modulated radiation therapy (IMRT): a retrospective review

Abstract\ud \ud Background\ud Ototoxicity is a known side effect of combined radiation therapy and cisplatin chemotherapy for the treatment of medulloblastoma. The delivery of an involved field boost by intensity modulated radiation therapy (IMRT) may reduce the dose to the inner ear when compared with conventional radiotherapy. The dose of cisplatin may also affect the risk of ototoxicity. A retrospective study was performed to evaluate the impact of involved field boost using IMRT and cisplatin dose on the rate of ototoxicity.\ud \ud \ud Methods\ud Data from 41 medulloblastoma patients treated with IMRT were collected. Overall and disease-free survival rates were calculated by Kaplan-Meier method Hearing function was graded according to toxicity criteria of Pediatric Oncology Group (POG). Doses to inner ear and total cisplatin dose were correlated with hearing function by univariate and multivariate data analysis.\ud \ud \ud Results\ud After a mean follow-up of 44 months (range: 14 to 72 months), 37 patients remained alive, with two recurrences, both in spine with CSF involvement, resulting in a disease free-survival and overall survival of 85.2% and 90.2%, respectively.\ud Seven patients (17%) experienced POG Grade 3 or 4 toxicity. Cisplatin dose was a significant factor for hearing loss in univariate analysis (p < 0.03). In multivariate analysis, median dose to inner ear was significantly associated with hearing loss (p < 0.01). POG grade 3 and 4 toxicity were uncommon with median doses to the inner ear bellow 42 Gy (p < 0.05) and total cisplatin dose of less than 375 mg/m2 (p < 0.01).\ud \ud \ud Conclusions\ud IMRT leads to a low rate of severe ototoxicity. Median radiation dose to auditory apparatus should be kept below 42 Gy. Cisplatin doses should not exceed 375 mg/m2.This study was supported by Instituto Israelita de Responsabilidade Social\ud (IIRS) of Hospital Israelita Albert Einstein (HIAE)

Peculiaridades da radioterapia em idosos Peculiarities of radiotherapy in the elderly

É sabido que o envelhecimento da população do mundo durante o século XX e no início deste novo século constitui um desafio de primeira ordem para as nações, especialmente no campo socioeconômico. Um aspecto importante do envelhecimento populacional global é que, para grupos de idade mais avançada, a prevalência das doenças degenerativas também é maior, incluindo as doenças malignas. No universo de pacientes portadores de câncer, por outro lado, metade destes receberá radioterapia em algum momento de sua doença e suas características individuais podem influenciar, de alguma forma, o prognóstico, a indicação e as doses diárias de prescrição dos tratamentos. Neste contexto, a assistência à saúde do idoso portador de câncer deve ser vista como um importante desafio, principalmente devido a dois fatores: uma maior procura de tratamentos, em termos quantitativos, e características fisiológicas peculiares a esta população, que podem influenciar na tomada de decisões terapêuticas. Esta revisão propõe uma discussão sobre alguns aspectos relevantes tanto da fisiologia dos idosos, que pode influenciar o curso do tratamento irradiante, quanto de alguns avanços técnicos da radioterapia, que podem, por sua vez, beneficiar estes pacientes, oferecendo menor toxicidade e maior eficiência e rapidez, por exemplo.<br>It is known that the aging of the world population during the twentieth century and the beginning of this new century is a first-order challenge for nations, especially in the socio-economic field. An important aspect of the aging of global population is that, for older age groups, the prevalence of degenerative diseases is also higher, including malignancies. On the other hand, among the population of patients with cancer, half of these patients will receive radiation therapy at some point in their illness and their individual characteristics can somehow influence the prognosis, the indication and daily doses of treatment prescriptions. In this context, the health assistance for the elderly patient with cancer should be seen as an important challenge, mainly due to two factors: an increased demand for treatments, in quantitative terms, and physiological characteristics unique to this population, which can influence the therapeutic decision-making. This review proposes a discussion of some relevant aspects of both the physiology of the elderly, which may influence the course of radiation therapy, as well as of some technical advances in radiotherapy, which can in turn benefit these patients by offering, for example, lower toxicity, greater effectiveness and speed

Unintended irradiation of internal mammary chain – Is that enough?

AimTo evaluate the unintentional coverage of the internal mammary chain (IMC) with tangential fields irradiation to the breast, and its relation with the type of surgery employed.BackgroundThe dose distribution in regions adjacent to the treatment targets (mammary gland or chest wall), with incidental irradiation of the IMC, could translate into clinical benefit, due to the proximity of these regions.Materials and methodsOne hundred and twelve consecutive conformal radiotherapy plans were correlating the average dose to the IMC with the type of surgery employed, the extent of disease and the irradiation techniques.ResultsThe mean doses to IMC after modified radical mastectomy (MRM), modified radical mastectomy with immediate reconstruction (MRM[[ce:hsp sp="0.25"/]]+[[ce:hsp sp="0.25"/]]R), and breast conservative surgery (BCS) were 30.34[[ce:hsp sp="0.25"/]]Gy, 30.26[[ce:hsp sp="0.25"/]]Gy, and 18.67[[ce:hsp sp="0.25"/]]Gy, respectively. Significant differences were identified between patients who underwent MRM or MRM[[ce:hsp sp="0.25"/]]+[[ce:hsp sp="0.25"/]]R over BCS (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.01 and 0.003, respectively), but not between MRM and MRM[[ce:hsp sp="0.25"/]]+[[ce:hsp sp="0.25"/]]R (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.88). Mean doses to IMC were greater in patients with T3–T4 tumors when compared with more initial stages (≤T2) (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.0096). The lymph node involvement also correlated with higher average doses to IMC (node positive: 26.1[[ce:hsp sp="0.25"/]]Gy[[ce:hsp sp="0.25"/]]×[[ce:hsp sp="0.25"/]]node negative: 17.8[[ce:hsp sp="0.25"/]]Gy, p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.0017).ConclusionsThe moderate dose level to the IMC in the unintentional irradiation scenario seems to be insufficient to treat the subclinical disease, although it could have an impact in patients undergoing mastectomy

Validating the SIR: a better prognostic score index for patients with brain metastases treated with stereotactic radiosurgery

Objective: The aim of this paper is to validate the score index forsurvival in patients treated with stereotactic radiosurgery, using aclassification prepared to better evaluate the prognosis of patientswith brain metastasis submitted to stereotactic surgery, re-evaluatingsurvival of patients and reviewing the medical literature. Methods:Data from 100 patients with brain metastases treated with stereotacticradiosurgery at a single institution, between July 1993 and February2000, were retrospectively analyzed. The prognostic factors andscores studied were age, Karnofsky performance status, extracranialdisease status, number of brain lesions, volume of the largest lesion,primary tumor type, treated or not with whole brain radiation therapy,SIR, and RPA. Kaplan-Meier actuarial survival curves for subsets werecalculated and compared by log-rank test. Complete and backwardelimination Cox models were utilized to identify the prognostic factorsand scores independently associated with survival. Results: Karnofskyperformance status, extracranial disease status, volume of the largestbrain lesion, RPA, and SIR were significantly correlated with prognosisin Kaplan-Meier survival analysis. Applying Cox models, significancewas observed for KPS and volume of the largest lesion (p < 0.0001and p = 0.0182, respectively), as well as for SIR and RPA when testedindividually (p < 0.0001 and p = 0.0002, respectively). However, whentesting SIR and RPA together, only SIR reached independent statisticalsignificance (p < 0.0001). Conclusion: SIR classification demonstrateda better accuracy in predicting survival time than RPA. SIR was testedin other centers, showing superior accuracy and applicability than theRPA, thus validating this score

INTENSITY-MODULATED AND 3D-CONFORMAL RADIOTHERAPY FOR WHOLE-VENTRICULAR IRRADIATION AS COMPARED WITH CONVENTIONAL WHOLE-BRAIN IRRADIATION IN THE MANAGEMENT OF LOCALIZED CENTRAL NERVOUS SYSTEM GERM CELL TUMORS

Purpose: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs). Methods and Materials: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a ""boost"" to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluated at dose levels ranging from 2 Gy to 40 Gy. Results: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels., compared with 3D-CRT. Intensity-modulated radiotherapy provided of 20, 30, and 40 Gy, respectively statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT. Conclusions: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment. (C) 2010 Elsevier Inc

Intensity-modulated ventricular irradiation for intracranial germ-cell tumors: Survival analysis and impact of salvage re-irradiation.

Background and purposeThe roles of surgery, chemotherapy, and parameters of radiation therapy for treating very rare central nervous system germ cell tumors (CNS-GCT) are still under discussion. We aimed to evaluate the survival and recurrence patterns of patients with CNS-GCT treated with chemotherapy followed by whole ventricle irradiation with intensity-modulated radiation therapy.Materials and methodsWe reviewed the clinical outcomes of 20 consecutive patients with CNS-GCT treated with chemotherapy and intensity-modulated radiation therapy from 2004 to 2014 in two partner institutions.ResultsTwenty children with a median age of 12 years were included (16 males). Sixteen tumors were pure germinomas, and 4 were non-germinomatous germ cell tumors (NGGCT). All patients were treated with intensity-modulated radiation therapy guided by daily images, and 70% with volumetric intensity-modulated arc radiotherapy additionally. The median dose for the whole-ventricle was 25.2 Gy (range: 18-30.6 Gy) and 36 Gy (range: 30-54 Gy) for the tumor bed boost. The median post-radiation therapy follow-up was 57.5 months. There were 3 recurrences (2 NGGCT and 1 germinoma that recurred as a NGGCT), with 1 death from the disease and the other 2 cases each successfully rescued with chemotherapy and craniospinal irradiation. The overall survival at 5 years was 95% and disease-free survival was 85%.ConclusionsThe results of this study suggest that the combined use of chemotherapy followed by whole ventricle irradiation with intensity-modulated radiation therapy is effective for CNS-GCTs, especially pure germinomas. Even being rescued with craniospinal irradiation, the NGGCT cases have markedly worse prognoses and should be more rigorously selected for localized treatment

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

BackgroundWhole 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.AimTo 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 Methods147 patients treated with a median follow up of 6.9 years (0.1⿿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⿤0.05 was considered statistically significant.ResultsOverall 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).ConclusionsIORT is a safe and effective treatment. Rigorous selection is important to achieve excellent local control results

Evaluation of biochemical response on early prostate cancer: comparison between treatment with external beam radiation alone and in combination with high-dose rate conformal brachytherapy boost

OBJECTIVE: To compare the biochemical response in patients with locally advanced prostate cancer treated with external beam radiation therapy alone or in combination with conformal brachytherapy boost. MATERIALS AND METHODS: From November 1997 to January 2000, 74 patients received 45 Gy of pelvic external irradiation and four were treated with high dose rate iridium-192 conformal boost implants of 4 Gy each (BT). These were compared with 29 other patients treated with 45 Gy of pelvic external irradiation followed by a 24 Gy of bilateral ARC boost (RT) from October 1996 to February 2000. Some patients received neoadjuvant androgen deprivation therapy. Three-year actuarial biochemical control rates (BC3) and pretreatment biochemical response predictors such as prostate-specific antigen pretreatment (PSAi), Gleason score (GS) and clinical stage (CS), were evaluated. RESULTS: Median follow-up was of 25 months for the RT group and 37 months for the BT group. BC3 was 51% versus 73% (p = 0.032) for RT and BT, respectively. Comparisons of biochemical control by treatment group stratified by PSAi showed that BC3 for RT versus BT was 85.7% versus 79.1% (p = 0.76) for PSAi 10 ng/mL, respectively. For patients with GS 6, BC3 was 78% versus 55% (p = 0.58) for RT versus BT, respectively. For patients with CS T2a, BC3 was 73% versus 69% (p = 0.692) for RT versus BT, respectively. The relative risk of biochemical relapse was 2.3 (95% IC: 1.0-5.1) for patients in RT group compared to the BT group. When adjusted for PSAi and GS, the relative risk of biochemical relapse was 2.4 (95% IC: 1.0-5.7). CONCLUSION: The treatment modality was an independent prognostic factor for biochemical relapse, with a significant improvement in the biochemical control with BT. These early results suggest that this treatment was most beneficial in patients with PSAi > 10 ng/mL, CS 10 ng/mL, respectivamente. Quando estratificado pelo EG, a SB3 para RT e BT foi de 37% e 80% (p = 0,001) para EG 6 (p = 0,58); estratificando-se pelo EC, a SB3 para RT e BT foi de 36% e 74% (p = 0,018) para EC T2a (p = 0,692), respectivamente. O risco relativo bruto de recidiva bioquímica foi de 2,3 (95% IC: 1,0-5,1) para os pacientes tratados com RT, em relação à BT; quando ajustado pelo PSAi e EG, o risco relativo de recidiva bioquímica foi de 2,4 (95% IC: 1,0-5,7). CONCLUSÃO: A modalidade de tratamento foi fator prognóstico independente de recidiva bioquímica, com maior controle bioquímico associado à BT. Nossos resultados preliminares sugerem que o maior benefício com BT foi obtido nos pacientes com PSAi > 10 ng/mL, EC < T2a e EG < 6.Hospital do Câncer A.C. Camargo Departamento de RadioterapiaUniversidade de São PauloHospital do Câncer A.C. Camargo Centro de EstudosUniversidade Metodista de Santos Faculdade de MedicinaHospital do Câncer A.C. CamargoUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaFaculdade de Medicina de MaríliaUNIFESP, EPMSciEL

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&ndash;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