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Background: This retrospective study aimed to investigate the outcomes and adverse events (AEs) associated with adjuvant radiotherapy with helical tomotherapy (hT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). Methods: Twenty-eight patients with DCIS underwent postoperative hT between 2011 and 2020. hT was chosen since it provided optimal target coverage and tolerable organ-at-risk doses to the lungs and heart when tangential 3-dimensional conformal radiotherapy (3D-CRT) was presumed to provide unfavorable dosimetry. The median total (single) dose was 50.4â Gy (1.8â Gy). The median time between BCS and the start of hT was 5 weeks (range, 4-38 weeks). Statistical analysis included local recurrence-free survival, overall survival (OS), and secondary cancer-free survival. AEs were classified according to the Common Toxicity Criteria for Adverse Events, version 5. Results: The patients' median age was 58 years. The median follow-up period was 61 months (range, 3-123 months). The 1-, 3-, and 5-year OS rates were 100% each. None of the patients developed secondary cancer, local recurrence, or invasive breast cancer during follow-up. The most common acute AEs were dermatitis (n = 27), fatigue (n = 4), hyperpigmentation (n = 3), and thrombocytopenia (n = 4). The late AE primarily included surgical scars (n = 7) and hyperpigmentation (n = 5). None of the patients experienced acute or late AEs > grade 3. The mean conformity and homogeneity indices were 0.9 (range, 0.86-0.96) and 0.056 (range, 0.05-0.06), respectively. Conclusion: hT after BCS for DCIS is a feasible and safe form of adjuvant radiotherapy for patients in whom 3D-CRT is contraindicated due to unfavorable dosimetry. During follow-up, there were no recurrences, invasive breast cancer diagnoses, or secondary cancers, while the adverse effects were mild.
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Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Mastectomia Segmentar , Radioterapia de Intensidade Modulada , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Idoso , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Carcinoma Intraductal não Infiltrante/radioterapia , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Adulto , Estudos Retrospectivos , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/patologia , Resultado do Tratamento , Dosagem Radioterapêutica , Seguimentos , Terapia CombinadaRESUMO
BACKGROUND: To retrospectively access outcome, adverse events and prognostic factors in oropharyngeal carcinoma (OPC) patients treated with intensity-modulated radiotherapy (IMRT). METHODS: Ninety-eight OPC patients were treated between 2000 and 2015. Thirty-three patients received definitive and 65 adjuvant radiotherapy. Seventy-one percent had simultaneous chemotherapy. Patients were systematically followed up (mean 114 months, range 19-197 months). Statistical analysis used Kaplan-Meier method, Cox regression analysis, and log-rank test. Adverse events were classified according to common toxicity criteria version (CTCAE) 4.03. RESULTS: The 1-, 5-, and 10-year overall survival rates in the adjuvant vs. definitive cohort were 90.8% vs. 66.7%, 67.4% vs. 33.1%, and 57.7% vs. 16.5%. Survival in the adjuvant cohort was significantly longer than in the definitive cohort (P < 0.00005). Patients <65 years had a significantly longer survival than older patients. Locoregional tumor control rates after 1-, 5-, and 10 years in the adjuvant vs. definitive cohort were 90.2% vs. 66.7%, 82.2% vs 45.4%, and 72.1% vs. 30.3%. Locoregional tumor control in the adjuvant cohort was significantly longer than in the definite cohort (P < 0.005). Distant metastases were diagnosed in 20.4% of all patients. Most patients had mild CTCAE grade 1 and 2 adverse events and mild late adverse events including xerostomia, dysphagia, and lymphedema. CONCLUSION: Intensity-modulated radiotherapy for OPC is an important part of the treatment algorithm alone and in particular after surgery while the additional benefits of chemotherapy might be age dependent. Despite advanced tumor stages, nearly half of our patients were alive in the long term. The majority of patients had relatively mild chronic adverse events.
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Carcinoma , Neoplasias Orofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/patologia , Radioterapia Adjuvante/efeitos adversos , Carcinoma/etiologiaRESUMO
BACKGROUND/AIM: To determine the interaction of gemcitabine in chemoradiotherapy with heavy carbon ions in vitro in a mucoepidermoid carcinoma (MEC) cell line. MATERIALS AND METHODS: The human lymphatic MEC metastasis cell line NCI-H292 was used. The cells were treated with photons, carbon ions, and gemcitabine. Survival fractions (SF), apoptosis, and cell cycle progression were analyzed. A paired two-sided t-test was used. Significance was defined as p<0.05. RESULTS: Cell proliferation assays showed a significant reduction in SF for combined photon chemoradiation versus photons only. The linear-quadratic fits of combined therapy with carbon ion dose of 0 to 2.5 Gy led to reductions of mean 15% in SF. The LD50 (lethal radiation dose required to reduce cell survival by 50%) for carbon ions only was 0.7 Gy and for carbon ions with gemcitabine 0.6 Gy. The LD50 for photons (with gemcitabine) was 2.8 Gy (2.0 Gy) and for carbon ions (with gemcitabine) 0.7 Gy (0.6 Gy), resulting in a relative biological effectiveness at 10% cell survival (RBE10) of 3.0 (2.7). Carbon ions and photons reduced S phase and increased G2/M phase cell distribution. Isolated treatment with gemcitabine as well as combination with photons led to prolonged S phase transit, whereas combined treatment with carbon ions led to early accumulation in G2/M phase. A significant increase in the sub-G1 population as a hint of relevant number of apoptotic cells was not observed. CONCLUSION: Gemcitabine showed radiosensitizing effects in combination with photons. The combination of gemcitabine and carbon ions had independent additive effects. Carbon ions only had a RBE10 of 3.0, compared to photons only. The combination of gemcitabine, photon, and carbon ions in patients with MEC seems promising and warrants further investigation.
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Carcinoma Mucoepidermoide , Radioterapia com Íons Pesados , Humanos , Gencitabina , Desoxicitidina/farmacologia , Carcinoma Mucoepidermoide/tratamento farmacológico , Linhagem Celular Tumoral , Radioterapia com Íons Pesados/métodos , Quimiorradioterapia/métodos , Fótons/uso terapêutico , Carbono/uso terapêutico , ÍonsRESUMO
BACKGROUND/AIM: Adjuvant radiotherapy is an integral part of the interdisciplinary curative treatment of breast cancer. We aimed to examine the long-term clinical results of helical tomotherapy in female patients with local restricted, lymph node negative breast cancer after breast-conserving surgery. PATIENTS AND METHODS: In this single-centre analysis, 219 female patients with early-stage breast cancer (T1/2) and no lymph node metastasis (N0) following breast-conserving surgery and sentinel-node biopsy were treated with adjuvant fractionated whole breast radiation therapy using helical tomotherapy. When boost irradiation was indicated, it was administered sequentially or using the simultaneous-integrated boost technique. Local control (LC), metastasis and survival rates, acute toxicity, late toxicity, and secondary malignancy rates were analysed retrospectively. RESULTS: The mean follow-up time was 71 months. The 5- and 8-year overall survival (OS) rates were 97.7% and 92.1%, respectively. The 5- and 8-year LC rates were 99.5% and 98.2%, while the 5- and 8-year metastasis-free survival (MFS) rates of 97.4% and 94.3%, respectively. Patients with G3 grading or negative hormone receptor status did not show significantly different results. Acute erythema occurred in 79% (grade 0-2) and 21% (grade 3) of the patients. Lymphedema of the ipsilateral arm and pneumonitis occurred in 6.4% and 1.8% of the treated patients. None of the patients developed >grade 3 toxicities during follow-up, while 1.8% developed a secondary malignancy during follow-up. CONCLUSION: Helical tomotherapy showed excellent long-term results and low toxicity rates. The incidence rates of secondary malignancy were relatively low and correlated with pre-existing data on radiotherapy, suggesting wider implementation of helical tomotherapy in adjuvant radiotherapy for breast cancer patients.
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Neoplasias da Mama , Radioterapia de Intensidade Modulada , Feminino , Humanos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Mastectomia Segmentar , Biópsia de Linfonodo Sentinela , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodosRESUMO
BACKGROUND: Surgery and radiotherapy are current therapeutic options for malignant tumors involving the nasal vestibule. Depending on the location, organ-preserving resection is not always possible, even for small tumors. Definitive radiotherapy is an alternative as an organ-preserving procedure. Carbon ion beam radiotherapy offers highly conformal dose distributions and more complex biological radiation effects eventually resulting in optimized normal tissue sparing and improved outcome. The aim of the current study was to analyze toxicity, local control (LC), and organ preserving survival (OPS) after irradiation of carcinoma of the nasal vestibule with raster-scanned carbon ion radiotherapy boost (CIRT-B) combined with volumetric intensity modulated arc therapy (VMAT) with photons. METHODS: Between 12/2015 and 05/2021, 21 patients with malignant tumors involving the nasal vestibule were irradiated with CIRT-B combined with VMAT and retrospectively analyzed. Diagnosis was based on histologic findings. A total of 17 patients had squamous cell carcinoma (SCC) and 4 had other histologies. In this series, 10%, 67%, and 24% of patients had Wang stages 1, 2, and 3 tumors, respectively. Three patients had pathologic cervical nodes on MRI. The median CIRT-B dose was 24 Gy(RBE), while the median VMAT dose was 50 Gy. All patients with pathologic cervical nodes received simultaneously integrated boost with photons (SIB) up to a median dose of 62.5 Gy to the pathological lymph nodes. Eight patients received cisplatin chemotherapy. All patients received regular follow-up imaging after irradiation. Kaplan-Meier estimation was used for statistical assessment. RESULTS: The median follow-up after irradiation was 18.9 months. There were no common toxicity criteria grade 5 or 4 adverse events. A total of 20 patients showed grade 3 adverse events mainly on skin and mucosa. All patients were alive at the end of follow-up. The median OPS after treatment was 56.5 months. The 6- and 24-month OPS were 100% and 83.3%, respectively. All local recurrences occurred within 12 months after radiotherapy. The median progression free survival (PFS) after treatment was 52.4 months. The 6-, 12-, and 24-month PFS rates were 95%, 83.6%, and 74.3%, respectively. CONCLUSION: CIRT-B combined with VMAT in malignant tumors of the nasal vestibule is safe and feasible, results in high local control rates, and thus is a good option as organ-preserving therapy. No radiation-associated grade 4 or 5 acute or late AE was documented.
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BACKGROUND/AIM: Casein kinase 2 (CK2) which sustains multiple pro-survival functions in cellular DNA-damage response, is strictly regulated in normal cells but elevated in cancer. CK2 is considered as a potential therapeutic target, and its inhibition has been associated with radiosensitization in mammalian cells in vitro. Here, we investigated potential radiosensitization by CK2 inhibition in vivo. MATERIALS AND METHODS: The effect of CK2 inhibition in vivo was investigated in human WiDr-xenograft tumours grown subcutaneously on BALB/c nu/nu mice with and without fractionated irradiation. CK2 inhibition was performed using the specific inhibitor tetra-bromobenzotriazole (TBB). Histological examinations included staining for apoptosis and double-strand breaks. RESULTS: Both TBB treatment alone and radiation alone significantly reduced tumour growth, which was reflected by increased apoptosis rates. However, TBB treatment did not boost radiation-induced tumour growth suppression in combined treatment, although the apoptosis rate increased and repair of double-strand breaks was reduced. This was in stark contrast to previous data on in vitro radiosensitization. CONCLUSION: The absence of radiosensitization by CK2 inhibition should be investigated in different tumour models.
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Caseína Quinase II , Neoplasias , Animais , Apoptose , Caseína Quinase II/genética , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos NusRESUMO
BACKGROUND/AIM: In percutaneous radiotherapy dose-distribution and volumetric-load of normal tissue varies in different radiation-techniques. Haematotoxicity may lead to deficiencies of the immune and blood system or to secondary malignancies. Therefore, regular blood-counts are carried out during fractionated radiotherapy. The aim was to investigate patient haemogram courses during radiotherapy of localised prostate-cancer treated with different radiation-techniques (n=3). PATIENTS AND METHODS: In this prospective study, blood count changes were examined during fractionated radiotherapy (3D-conformal-RT/step-and-shoot-IMRT/helical-IMRT) on the prostate-region in localised prostate-cancer cases (n=50). RESULTS: The whole patient group displayed a small but significant reduction in leukocytes. This reduction was higher in the two IMRT groups compared to the 3D-group but without any case of leukopenia. Haemoglobin- or thrombocyte-levels did not significantly change. CONCLUSION: Regardless of the delivery mode used, localised fractionated irradiation of prostate region did not cause any clinically relevant haemogram changes in this study. These findings question the necessity of regular blood counts during fractionated radiotherapy of the prostate region for patients without any risk factors.
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Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Relação Dose-Resposta à Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/sangue , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia Conformacional/efeitos adversos , Radioterapia Conformacional/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Patients with recurrent glioma after prior radiotherapy have a poor prognosis. Carbon ion beam radiotherapy offers highly conformal dose distributions and more complex biological radiation effects eventually resulting in optimized normal tissue sparing and improved outcome. The aim of this study was to analyze toxicity, local control and overall survival after reirradiation of recurrent high-grade glioma with carbon ion radiotherapy. METHODS: Between 10/2015 and 12/2018, 30 patients (median age: 59 years) with recurrent high-grade glioma were reirradiated with carbon ion beams and retrospectively analyzed. Diagnosis of recurrent glioma was based on magnetic resonance imaging. Thirteen patients had repeated resection prior to reirradiation and 24 patients underwent additional chemotherapy. The median initial radiation dose was 60 Gy and the median time interval between the initial and repeated radiotherapy was 10 months. The reirradiation dose was 45 Gy (relative biological effectiveness) applied in 15 fractions. All patients received regular follow-up imaging after reirradiation. Kaplan-Meier estimation, log rank test and Cox regression analysis were used for statistical assessment. RESULTS: Applying common toxicity criteria, there were no grade 5 or 4 adverse events, while 8 patients showed grade 3 adverse events. The median follow-up after reirradiation was 11 months and the median overall survival after diagnosis of recurrent high-grade glioma was 13 months. The 6-, 12- and 24-month overall survival rates after diagnosis of recurrent high-grade glioma were 76%, 50% and 19%, respectively. Upon multivariate Cox regression analysis, a Ki67 score of the initial tumor histology of less than 20% was prognostic. Repeated resection or chemotherapy for the recurrent disease did not result in significantly prolonged survival. CONCLUSION: Carbon ion reirradiation in recurrent high-grade glioma is safe and feasible. No radiation-associated grade 4 toxicities were documented and treatment was tolerated well.
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PURPOSE: The adenoid cystic carcinoma (ACC), Erbitux, and Particle Therapy (ACCEPT) phase 1/2 trial (NCT01192087) evaluated a combined-modality approach (concurrent cetuximab and intensity modulated radiation therapy with carbon ion boost) for newly diagnosed nonmetastatic head and neck ACC. METHODS AND MATERIALS: Twenty-three patients with ACC were enrolled between June 2012 and June 2017 after initial diagnosis or postoperatively. All received a 400 mg/m2 cetuximab loading dose a week before radiation therapy, followed by weekly 250 mg/m2 doses starting on the first day of radiation therapy. The carbon ion radiation therapy boost was 24 Gy (relative biological effectiveness) in 8 daily fractions, followed by intensity modulated radiation therapy (54 Gy). The primary endpoint was safety and feasibility (defined based on Common Terminology Criteria for Adverse Events grade ≥3 events). Secondary endpoints included local and distant relapse, disease-free survival, and overall survival. RESULTS: Disease was most commonly in the paranasal sinuses (30%), palate (17%), and nasopharynx (17%). Nine (39%) patients underwent surgery (R1: 22%, R2: 78%). Median follow-up was 38.5 months. No patients experienced grade 4 to 5 events. Rates of grade 3 rash and radiation dermatitis were 17% and 22%, respectively. Grade 2 and 3 mucositis and dysgeusia occurred in 43% and 48% and in 9% and 0%, respectively. Grade 2 to 3 dysphagia and xerostomia were present in 43% and 4% and in 26% and 0%, respectively. At last follow-up, 5 (22%) patients experienced in-field relapse and 6 (26%) developed distant metastases. The 3-year disease-free survival was 67%, and median overall survival was 54 months. CONCLUSIONS: Outcomes of this trial were satisfactory. Although the trial did not meet the predefined criteria of feasibility owing to the comparatively high rates of grade 3 dermatitis, numbers are comparable to existing data on cetuximab + radiation therapy.
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Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Adenoide Cístico/terapia , Cetuximab/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias de Cabeça e Pescoço/terapia , Radioterapia com Íons Pesados , Radioterapia de Intensidade Modulada , Antineoplásicos Imunológicos/administração & dosagem , Carcinoma Adenoide Cístico/patologia , Cetuximab/administração & dosagem , Quimiorradioterapia/efeitos adversos , Terapia Combinada/métodos , Transtornos de Deglutição/etiologia , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Esquema de Medicação , Estudos de Viabilidade , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Radioterapia com Íons Pesados/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Radiodermite/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Eficiência Biológica Relativa , Xerostomia/etiologiaRESUMO
Purpose: Due to the sharp gradients of intensity-modulated radiotherapy (IMRT) dose distributions, treatment uncertainties may induce substantial deviations from the planned dose during irradiation. Here, we investigate if the planned mean dose to parotid glands in combination with the dose gradient and information about anatomical changes during the treatment improves xerostomia prediction in head and neck cancer patients. Materials and methods: Eighty eight patients were retrospectively analyzed. Three features of the contralateral parotid gland were studied in terms of their association with the outcome, i.e., grade ≥ 2 (G2) xerostomia between 6 months and 2 years after radiotherapy (RT): planned mean dose (MD), average lateral dose gradient (GRADX), and parotid gland migration toward medial (PGM). PGM was estimated using daily megavoltage computed tomography (MVCT) images. Three logistic regression models where analyzed: based on (1) MD only, (2) MD and GRADX, and (3) MD, GRADX, and PGM. Additionally, the cohort was stratified based on the median value of GRADX, and a univariate analysis was performed to study the association of the MD with the outcome for patients in low- and high-GRADX domains. Results: The planned MD failed to recognize G2 xerostomia patients (AUC = 0.57). By adding the information of GRADX (second model), the model performance increased to AUC = 0.72. The addition of PGM (third model) led to further improvement in the recognition of the outcome (AUC = 0.79). Remarkably, xerostomia patients in the low-GRADX domain were successfully identified (AUC = 0.88) by the MD alone. Conclusions: Our results indicate that GRADX and PGM, which together serve as a proxy of dosimetric changes, provide valuable information for xerostomia prediction.
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Background: Patients with multiple brain metastases (BMs) from malignant melanoma have a poor prognosis. Recent developments in radiation techniques allow simultaneous integrated boost (SIB) concepts while sparing organs at risk. Data on conventional versus dose-escalated radiation approaches in multiple BMs from malignant melanoma are warranted. Methods: In this prospective, single-center, randomized two-armed study (trial ID: DRKS00005127), patients with multiple BMs from malignant melanoma were treated with either conventional whole-brain radiotherapy (WBRT) applying 30 Gy in 10 fractions (standard arm) or helical tomotherapy applying 30 Gy to the whole brain with an integrated boost to metastases of 50 Gy in 10 fractions and sparing of the hippocampus (HA-WBRT, experimental arm). The primary endpoint was treatment-related toxicity, while secondary endpoints were imaging response, intracerebral progression-free survival (PFS), overall survival (OS) and quality of life. Results: The study was stopped early due to slow patient recruitment. A total number of 7 patients were enrolled (standard arm n=3, experimental arm n=4), and were followed-up for a median time of 5 months between August 2013 and July 2017. All patients were treated according to protocol. The median OS, intracerebral PFS and follow-up time were 5 months, 2 months and 5 months, respectively. The local control in every individual BM was significantly longer in the experimental versus the standard arm. No patient developed radiation-related high-grade toxicities. Conclusion: HA-WBRT with SIB results in improved local control in the individual melanoma BMs without radiation-associated high-grade toxicities. Survival times were comparable to published data.
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Dimethyl sulfoxide (DMSO) is an effective radical scavenger and, when added to cells, reduces the initial number of radiation-induced DNA double-strand breaks (DSB). The aim of this study was to investigate modification by DMSO of both DSB induction and DSB repair by means of pulsed-field gel electrophoresis (PFGE) as well as gamma-H2AX immunofluorescence staining. WiDr cells (human colon carcinoma provided by DKFZ) were incubated with 2% DMSO for 2 h (or mock-treated) prior to irradiation with varying X-ray doses and subsequent incubation for repair. Sample processing for PFGE analysis or counting of γ-H2AX foci was performed according to standard protocols. Effects on apoptosis induction and cell survival were investigated additionally by standard protocols. DMSO reduced DSB yield after 20-80 Gy measured by PFGE. A qualitatively similar result was found after low-dose irradiation (1 Gy) using γ-H2AX immunofluorescence staining. During incubation for repair, both DNA fragment rejoining (PFGE) as well as γ-H2AX foci removal occurred at a reduced rate when cells had been pre-treated with DMSO. But this effect was clearly more pronounced for the PFGE-analyzed double-strand breakage, particularly at early repair times. WiDr cells treated with DMSO (2%) showed a significantly increased clonogenic survival after irradiation doses above 8 Gy. Apoptosis rates were not changed by DMSO. The radio-protective effect of DMSO, well known from other PFGE studies, could be confirmed for the formation of γ-H2AX foci. DSB generated in the presence of DMSO were less rapidly repaired. DMSO showed radio-protective effects on clonogenic survival but not on apoptosis.
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Dimetil Sulfóxido/química , Relação Dose-Resposta à Radiação , Sequestradores de Radicais Livres/química , Apoptose , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , DNA/efeitos da radiação , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Dano ao DNA , Reparo do DNA/efeitos dos fármacos , Eletroforese em Gel de Campo Pulsado , Humanos , Protetores contra Radiação/químicaRESUMO
BACKGROUND: The purpose of this retrospective analysis is to analyze clinical outcome, visual acuity and enucleation rates after linear accelerator-based stereotactic fractionated photon radiotherapy for primary uveal melanoma. METHODS: Twenty-four patients with primary uveal melanoma treated at the Department of Radiation and Oncology of the University Hospital Heidelberg between 1991 and 2015 were analyzed regarding survival and treatment-related toxicity including eye- and sight-preservation. RESULTS: Photon radiotherapy (RT) offered good overall local control rates with a local progression-free survival (LPFS) of 82% after 5 years and a median LPFS of 5.5 years at a median follow-up time of 5.2 years. Gender had a significant impact on LPFS yielding a mean LPFS of 8.1 years for women and 8.7 years for men (p = 0.04). Of all local progressions, 80% occurred within the first 5 years after RT. In one case, enucleation as final therapy option was necessary. Enucleation-free survival (EFS) was related to the radiotherapy dose (p < 0.0001). Thus, higher prescribed doses led to a significantly higher enucleation rate. T-stage had no significant impact on EFS, but affected the enucleation rate (p = 0.01). The overall survival (OS) rate was 100% after 2 years and 70% after 5 years with a median OS of 5.75 years. Age (p = 0.046), T stage (p = 0.019), local control rate (p = 0.041) and the time between diagnosis and the first radiation session (p = 0.01) had a significant effect on OS. Applied biologically effective dose (BED) did not significantly influence OS or PFS. A 2-year sight preservation rate of 75% could be achieved. In all patients, irradiation could be applied safely without any interruptions due to side effects. Six significant late toxicities with consequential blindness could be observed, making a secondary enucleation necessary in four patients. An impairment of visual acuity due to chronic optic nerve atrophy was identified in five patients within 2 years after treatment. CONCLUSIONS: Linear accelerator-based stereotactic fractionated photon radiotherapy is an effective method in the treatment of uveal melanoma with excellent local control rates and a 2-year vision retention rate comparable to brachytherapy (BRT) or proton beam radiotherapy, even available in small centers and easy to implement. Interdisciplinary decision making is necessary to guarantee best treatment for every patient.
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Olho , Melanoma/radioterapia , Tratamentos com Preservação do Órgão/métodos , Fótons/uso terapêutico , Radioterapia/métodos , Neoplasias Uveais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Aceleradores de Partículas , Fótons/efeitos adversos , Intervalo Livre de Progressão , Radioterapia/efeitos adversos , Radioterapia/instrumentação , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento , Neoplasias Uveais/mortalidade , Acuidade VisualRESUMO
BACKGROUND: Neurosurgical resection is recommended for symptomatic brain metastases, in oligometastatic patients or for histology acquisition. Without adjuvant radiotherapy, roughly two-thirds of the patients relapse at the resection site within 24 mo, while the risk of new metastases in the untreated brain is around 50%. Adjuvant whole-brain radiotherapy (WBRT) can reduce the risk of both scenarios of recurrence significantly, although the associated neurocognitive toxicity is substantial, while stereotactic radiotherapy (SRT) improves local control at comparably low toxicity. OBJECTIVE: To compare locoregional control and treatment-associated toxicity for postoperative SRT and WBRT after the resection of 1 brain metastasis in a single-center prospective randomized study. METHODS: Fifty patients will be randomized to receive either hypofractionated SRT of the resection cavity and single- or multisession SRT of all unresected brain metastases (up to 10 lesions) or WBRT. Patients will be followed-up regularly and the primary endpoint of neurological progression-free survival will be assessed by magnetic resonance imaging (MRI). Quality of life and neurocognition will be assessed in 3-mo intervals using standardized tests and EORTC questionnaires. EXPECTED OUTCOMES: We expect to show that postoperative SRT of the resection cavity and further unresected brain metastases is a valid means of improving locoregional control over observation at less neurocognitive toxicity than caused by WBRT. DISCUSSION: The present study is the first to compare locoregional control as well as neurocognitive toxicity for postoperative SRT and WBRT in patients with up to 10 metastases, while utilizing a highly sensitive and standardized MRI protocol for treatment planning and follow-up.
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Neoplasias Encefálicas/terapia , Irradiação Craniana/métodos , Recidiva Local de Neoplasia/terapia , Cuidados Pós-Operatórios/métodos , Radiocirurgia/métodos , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Encéfalo/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Irradiação Craniana/tendências , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Cuidados Pós-Operatórios/tendências , Intervalo Livre de Progressão , Estudos Prospectivos , Qualidade de Vida , Radiocirurgia/tendências , Dosagem Radioterapêutica , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante/tendênciasRESUMO
PURPOSE: The purpose of this study is to investigate whether machine learning with dosiomic, radiomic, and demographic features allows for xerostomia risk assessment more precise than normal tissue complication probability (NTCP) models based on the mean radiation dose to parotid glands. MATERIAL AND METHODS: A cohort of 153 head-and-neck cancer patients was used to model xerostomia at 0-6 months (early), 6-15 months (late), 15-24 months (long-term), and at any time (a longitudinal model) after radiotherapy. Predictive power of the features was evaluated by the area under the receiver operating characteristic curve (AUC) of univariate logistic regression models. The multivariate NTCP models were tuned and tested with single and nested cross-validation, respectively. We compared predictive performance of seven classification algorithms, six feature selection methods, and ten data cleaning/class balancing techniques using the Friedman test and the Nemenyi post hoc analysis. RESULTS: NTCP models based on the parotid mean dose failed to predict xerostomia (AUCs < 0.60). The most informative predictors were found for late and long-term xerostomia. Late xerostomia correlated with the contralateral dose gradient in the anterior-posterior (AUC = 0.72) and the right-left (AUC = 0.68) direction, whereas long-term xerostomia was associated with parotid volumes (AUCs > 0.85), dose gradients in the right-left (AUCs > 0.78), and the anterior-posterior (AUCs > 0.72) direction. Multivariate models of long-term xerostomia were typically based on the parotid volume, the parotid eccentricity, and the dose-volume histogram (DVH) spread with the generalization AUCs ranging from 0.74 to 0.88. On average, support vector machines and extra-trees were the top performing classifiers, whereas the algorithms based on logistic regression were the best choice for feature selection. We found no advantage in using data cleaning or class balancing methods. CONCLUSION: We demonstrated that incorporation of organ- and dose-shape descriptors is beneficial for xerostomia prediction in highly conformal radiotherapy treatments. Due to strong reliance on patient-specific, dose-independent factors, our results underscore the need for development of personalized data-driven risk profiles for NTCP models of xerostomia. The facilitated machine learning pipeline is described in detail and can serve as a valuable reference for future work in radiomic and dosiomic NTCP modeling.
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BACKGROUND: The current study compares the results of irradiation with protons and irradiation with carbon ions via a raster scan technique in patients with G1 and G2 skull base chondrosarcomas. METHODS: Between 2009 and 2014, a total of 101 patients (40 men and 61 women) with a median age of 44 years (range, 19-77 years) were irradiated with carbon ions (79 patients) or protons (22 patients) via a raster scan technique at the Heidelberg Ion Beam Therapy Center. The median total dose was 60 Gy (relative biological effectiveness [RBE]) at 3 Gy per fraction for carbon ions and 70 Gy (RBE) at 2 Gy per fraction for protons. The median boost planning target volume was 38 cm3 (range, 8-133 cm3 ). Overall survival (OS) and local control (LC) were evaluated with the Kaplan-Meier method. RESULTS: The median follow-up period was 40 months (range, 0.8-78.1 months). At the start of the irradiation, all patients had residual macroscopic tumors. Five patients (5%) developed a local recurrence during the follow-up. The 1-, 2-, and 4-year LC rates were 100%, 100%, and 100%, respectively, for protons and 98.6%, 97.2%, and 90.5%, respectively, for carbon ions. The OS rates during the same periods of time were 100%, 100%, and 100%, respectively, for protons and 100%, 98.5%, and 92.9%, respectively, for carbon ions. An age ≤ 44 years was associated with a trend for a better outcome. No toxicity worse than Common Toxicity Criteria grade 3 was observed after treatment. CONCLUSIONS: No significant difference between carbon ions and protons in the therapy of skull base chondrosarcoma could be detected in these initial retrospective results. Cancer 2018;124:2036-44. © 2018 American Cancer Society.
Assuntos
Radioisótopos de Carbono , Condrossarcoma/radioterapia , Radioterapia com Íons Pesados/métodos , Prótons , Radioterapia de Intensidade Modulada/métodos , Neoplasias da Base do Crânio/radioterapia , Adulto , Fatores Etários , Idoso , Condrossarcoma/mortalidade , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Alemanha/epidemiologia , Radioterapia com Íons Pesados/efeitos adversos , Radioterapia com Íons Pesados/instrumentação , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/instrumentação , Estudos Retrospectivos , Neoplasias da Base do Crânio/mortalidade , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To investigate the incidence rate, time-to-onset and recovery, MRI morphology and occurrence of insufficiency fractures in radiation-induced changes in the sacrum following pelvic radiotherapy. MATERIAL AND METHODS: 410 patients with pelvic malignancies treated with radiotherapy were reviewed. Follow-up was 1-124 months (mean 22 months). Serial MRI (average four studies/patient) were analysed using a new semi-quantitative score (Radiation-Induced Sacral Changes=RISC). A size category (I/II/III), a type category for MR signal morphologies (a/b/c) and sacral insufficiency fractures (+/-) were applied. RESULTS: Seventy-two patients (17.6 %) were found to have new pathological signal changes. Radiation osteitis was documented in 83.3 % (60/72, RISC stage a + b), and definite osteonecrosis (stage c) in 12 patients (16.7 %, 12/72). Thirty-one patients (43.1 %) had sacral insufficiency fractures. Initial bone marrow signal changes were found 1-35 months (median 4 months) after radiotherapy. The maximum manifestation of radiation-induced signal changes occurred after 1-35 months (mean 11 months). Fifty-six cases (77.8 %) showed a significant signal recovery within 16.5 months. CONCLUSION: Radiation-induced bone marrow changes appear with a high incidence at the sacrum with an early onset and frequent recovery. The majority presented a pattern of radiation osteitis, whereas osteoradionecrosis was proportionately rare. KEY POINTS: ⢠Radiation-induced sacral bone marrow changes appear frequently (17.6 %) following pelvic radiotherapy. ⢠Insufficiency fractures are common late effects (43 %). ⢠Radiation osteitis develops early (4 mo), with recovery between 16.5 and 39.5 months. ⢠Definite radiological osteoradionecrosis is proportionately rare (3 %). ⢠A 3-stage classification system simplifies and standardizes the morphological disease staging.
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Fraturas de Estresse/epidemiologia , Imageamento por Ressonância Magnética/métodos , Osteíte/epidemiologia , Osteorradionecrose/epidemiologia , Neoplasias Pélvicas/radioterapia , Lesões por Radiação/epidemiologia , Sacro/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Causalidade , Comorbidade , Feminino , Seguimentos , Fraturas de Estresse/diagnóstico por imagem , Fraturas de Estresse/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Osteíte/diagnóstico por imagem , Osteorradionecrose/diagnóstico por imagem , Osteorradionecrose/patologia , Pelve , Lesões por Radiação/diagnóstico por imagem , Radiografia , Estudos Retrospectivos , Fatores de Risco , Sacro/diagnóstico por imagem , Sacro/efeitos da radiação , Fatores de Tempo , Adulto JovemRESUMO
PURPOSE: Xerostomia is a common side effect of radiotherapy resulting from excessive irradiation of salivary glands. Typically, xerostomia is modeled by the mean dose-response characteristic of parotid glands and prevented by mean dose constraints to either contralateral or both parotid glands. The aim of this study was to investigate whether normal tissue complication probability (NTCP) models based on the mean radiation dose to parotid glands are suitable for the prediction of xerostomia in a highly conformal low-dose regime of modern intensity-modulated radiotherapy (IMRT) techniques. MATERIAL AND METHODS: We present a retrospective analysis of 153 head and neck cancer patients treated with radiotherapy. The Lyman Kutcher Burman (LKB) model was used to evaluate predictive power of the parotid gland mean dose with respect to xerostomia at 6 and 12 months after the treatment. The predictive performance of the model was evaluated by receiver operating characteristic (ROC) curves and precision-recall (PR) curves. RESULTS: Average mean doses to ipsilateral and contralateral parotid glands were 25.4 Gy and 18.7 Gy, respectively. QUANTEC constraints were met in 74% of patients. Mild to severe (G1+) xerostomia prevalence at both 6 and 12 months was 67%. Moderate to severe (G2+) xerostomia prevalence at 6 and 12 months was 20% and 15%, respectively. G1 + xerostomia was predicted reasonably well with area under the ROC curve ranging from 0.69 to 0.76. The LKB model failed to provide reliable G2 + xerostomia predictions at both time points. CONCLUSIONS: Reduction of the mean dose to parotid glands below QUANTEC guidelines resulted in low G2 + xerostomia rates. In this dose domain, the mean dose models predicted G1 + xerostomia fairly well, however, failed to recognize patients at risk of G2 + xerostomia. There is a need for the development of more flexible models able to capture complexity of dose response in this dose regime.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Glândula Parótida/patologia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Xerostomia/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Parótida/efeitos da radiação , Curva ROC , Dosagem Radioterapêutica , Estudos Retrospectivos , Xerostomia/etiologiaRESUMO
PURPOSE: To evaluate whether quantitative susceptibility (QSM) may be used as an alternative to computed tomography (CT) to detect calcification in prostate cancer patients. MATERIALS AND METHODS: Susceptibility map calculation was performed using 3D gradient echo magnetic resonance imaging (MRI) data from 26 patients measured at 3T who previously received a planning CT of the prostate. Phase images were unwrapped using Laplacian-based phase unwrapping, the background field was removed with the V-SHARP method, and susceptibility maps were calculated with the iLSQR method. Two blinded readers were asked to identify peri- and intraprostatic calcifications. RESULTS: Average mean and minimum susceptibility values (referenced to iliopsoas muscle) of calcifications were -0.249 ± 0.179 ppm and -0.551 ± 0.323 ppm, and average mean and maximum intensities in CT images were 319 ± 164 HU and 679 ± 392 HU. Twenty-one and 17 out of 22 prostatic calcifications were identified using susceptibility maps and magnitude images, respectively, as well as more than half of periprostatic phleboliths depicted by CT. Calcifications in the prostate and its periphery were quantitatively differentiable from noncalcified prostate tissue in CT (mean values for calcifications / for noncalcified tissue: 71 to 649 / -1 to 83 HU) and in QSM (mean values for calcifications / for noncalcified tissue: -0.641 to 0.063 / -0.046 to 0.181 ppm). Moreover, there was a significant correlation between susceptibility values and CT image intensities for calcifications (P < 0.004). CONCLUSION: Prostatic calcifications could be well identified with QSM. Susceptibility maps can be easily obtained from clinical prostate MR protocols that include a 3D gradient echo sequence, rendering it a promising technique for detection and quantification of intraprostatic calcifications. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:889-898.
Assuntos
Calcinose/diagnóstico por imagem , Calcinose/patologia , Imageamento por Ressonância Magnética/métodos , Lesões Pré-Cancerosas/diagnóstico por imagem , Lesões Pré-Cancerosas/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Adulto , Idoso , Estudos de Viabilidade , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
This case report shows the high PSMA-uptake in a patient with an adenoid cystic carcinoma of the maxillary sinus. Due to the intense ligand-uptake additional information for target volume delineation was obtained and the Treatment plan for bimodal radiotherapy with carbon ions was adapted accordingly.