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PURPOSE: Magnetic resonance-guided radiotherapy (MRgRT) has recently been introduced in our institution. As MRgRT requires high patient compliance compared to conventional techniques and can be associated with prolonged treatment times, feasibility and patient tolerance were prospectively assessed using patient-reported outcome questionnaires (PRO-Q). MATERIALS AND METHODS: Forty-three patients were enrolled in a prospective observational study and treated with MRgRT on a low-field hybrid Magnetic Resonance Linear Accelerator system (MR-Linac) between April 2018 and April 2019. For assistance in gated breath-hold delivery using cine-MRI, a video feedback system was installed. PRO-Qs consisted of questions on MR-related complaints and also assessed aspects of active patient participation. RESULTS: The most commonly treated anatomic sites were nodal metastases and liver lesions. The mean treatment time was 34â¯min with a mean beam-on time of 2:17â¯min. Gated stereotactic body radiotherapy (SBRT) was applied in 47% of all patients. Overall, patients scored MRgRT as positive or at least tolerable in the PROQ. Almost two thirds of patients (65%) complained about at least one item of the PROQ (score ≥4), mainly concerning coldness, paresthesia, and uncomfortable positioning. All patients reported high levels of satisfaction with their active role using the video feedback system in breath-hold delivery. CONCLUSION: MRgRT was successfully implemented in our clinic and well tolerated by all patients, despite MR-related complaints and complaints about uncomfortable immobilization. Prospective clinical studies are in development for further evaluation of MRgRT and for quantification of the benefit of MR-guided on-table adaptive radiotherapy.
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Imagen por Resonancia Magnética , Neoplasias/radioterapia , Aceptación de la Atención de Salud , Radioterapia Guiada por Imagen , Adulto , Anciano , Anciano de 80 o más Años , Fraccionamiento de la Dosis de Radiación , Estudios de Factibilidad , Femenino , Retroalimentación Formativa , Alemania , Personal de Salud/psicología , Humanos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/psicología , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico por imagen , Neoplasias/psicología , Aceleradores de Partículas , Medición de Resultados Informados por el Paciente , Estudios Prospectivos , Radiocirugia , Radioterapia Guiada por Imagen/psicologíaRESUMEN
BACKGROUND: Despite a lack of evidence and low compliance, current guidelines recommend the use of a vaginal dilator (VD) after pelvic radiotherapy (RT). We analyzed the effect of VD on vaginal stenosis (VS) and its influence on sexual quality of life (QoL) in women treated with adjuvant RT for endometrial cancer (EC). METHODS: Between 2014 and 2015, 56 consecutive patients were instructed to use a VD after completion of treatment. The maximum diameter of the comfortably introducible VD was measured before and at 1 year after treatment. The degree of VS was evaluated clinically, and sexual QoL was assessed with the European Organisation for Research and Treatment of Cancer (EORTC) sexual functioning items before RT, during RT, at 6 weeks, and at 1 year after RT. RESULTS: One year after RT, mean VD diameter had decreased by 2.7⯱ 3.2â¯mm (pâ¯< 0.001) and 36 patients (64.3%) had clinical VS (grade I-III). A larger decrease in VD diameter correlated with a higher degree of clinical VS (pâ¯< 0.001). VD use (pâ¯= 0.81), RT modality (pâ¯= 0.68), and adjuvant ChT (pâ¯= 0.87) had no influence on VD diameter. Sexual activity decreased during RT and increased beyond pre-RT values 1 year after RT (pâ¯< 0.001). Sexual enjoyment decreased continuously during and after completion of RT (pâ¯= 0.013) and was influenced negatively by a higher degree of clinical VS (pâ¯= 0.01). CONCLUSION: Almost two thirds of patients developed clinical VS 1 year after adjuvant RT for EC, and sexual enjoyment was substantially reduced by VS. The use of a VD after RT may not serve to prevent sexual impairments and VS.
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Adenocarcinoma/terapia , Dilatación/instrumentación , Neoplasias Endometriales/radioterapia , Orgasmo/efectos de la radiación , Traumatismos por Radiación/terapia , Vagina/efectos de la radiación , Enfermedades Vaginales/terapia , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Constricción Patológica/etiología , Constricción Patológica/terapia , Relación Dosis-Respuesta en la Radiación , Neoplasias Endometriales/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Cooperación del Paciente , Calidad de Vida , Traumatismos por Radiación/etiología , Enfermedades Vaginales/etiologíaRESUMEN
PURPOSE: To assess radiotherapy (RT) outcomes in patients with gingival carcinoma and growth up to or involvement of the lower jaw bone. METHODS: This was a retrospective analysis of 51 patients with squamous cell carcinomas of the gingiva. Patients received definitive (group 1, 31.4%) or postoperative (group 2, 66.7%) RT between 2005 and 2017â¯at the Department of Radiation Oncology, University Hospital Heidelberg. The primary endpoint was overall survival (OS) in both treatment groups. Other endpoints were local-disease-free survival (LDFS), progression-free survival (PFS) and treatment-related toxicity (Common Terminology Criteria for Adverse Events, CTCAE, Version 4.03). RESULTS: Median age at first diagnosis was 63 years. All patients had a local advanced disease (American Joint Commission on Cancer [AJCC] stage III-IV). After a median follow-up of 22 months (range 3-145 months), 20 patients (39.2%) were still alive. At 5 years, OS rate was 36.6%. No significant differences in OS (pâ¯= 0.773), PFS (pâ¯= 0.350) and LDFS (pâ¯= 0.399) were observed between the two groups. Most common higher-grade acute RT-related complications (≥ grade 3) were dermatitis (78.2%), oral mucositis (61.7%), xerostomia (51.5%), and loss of taste (74.6%). Three cases (5.8%) of osteoradionecrosis (ORN) of the lower jaw were detected after 15-31 months. CONCLUSIONS: Definitive and postoperative RT have similar treatment outcomes for patients with lower gingiva carcinomas of the lower jaw. The most common acute complications (grade ≥3) were dermatitis, oral mucositis, xerostomia and loss of taste.
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Carcinoma de Células Escamosas/radioterapia , Neoplasias Gingivales/radioterapia , Neoplasias Mandibulares/radioterapia , Traumatismos por Radiación/etiología , Radioterapia Adyuvante , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Terapia Combinada , Neoplasias Gingivales/mortalidad , Neoplasias Gingivales/patología , Neoplasias Gingivales/cirugía , Humanos , Masculino , Neoplasias Mandibulares/mortalidad , Neoplasias Mandibulares/patología , Neoplasias Mandibulares/cirugía , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Supervivencia sin Progresión , Traumatismos por Radiación/mortalidad , Resultado del TratamientoRESUMEN
PURPOSE: This retrospective study aimed to evaluate the stability and fracture rates of osteolytic spinal bone metastases (SBM) in elderly patients following palliative radiotherapy (RT) and to derive prognostic factors for stability and survival. METHODS: A total of 322 patients aged at least 70 years received palliative RT at two major German academic medical centers or at the German Cancer Research Center. Stability assessment was based on the validated Taneichi score prior to RT and at 3 and 6 months after RT. The survival time following RT was assessed, and prognostic factors for stability and survival were analyzed. RESULTS: Prior to RT, 183 patients (57%) exhibited unstable SBM and 68 patients (21%) pathological fractures. At 3 and 6 months after RT, significant recalcification and stabilization were evident in 19% (23/118) and 40% (31/78) of surviving patients, respectively. Only 17 patients (5%) experienced new pathological fractures following RT. Tumor histology was found to significantly influence stabilization rates with only breast cancer patients exhibiting increased stabilization compared to patients with other histologies. The median survival time and 6month survival rates following RT were 5.4 months (95% confidence interval 4.4-7.2 months) and 48%, respectively. The patients' performance status was found to be the strongest predictor for survival after RT in this patient cohort; further factors demonstrating a significant association with survival were the application of systemic treatment, the number of SBM and the primary tumor histology. To analyze the influence of age on survival after RT, study patients were stratified into 3 age groups (i.e., 70-74 years, 75-79 years, and ≥80 years). The subgroup of patients aged at least 80 years showed a strong trend towards a worse survival time following RT compared to younger patients (i.e., 6month survival rate 39% vs. 51%; pâ¯= 0.06, log-rank test). CONCLUSIONS: Prognostic factors influencing overall survival such as performance status and histology should guide the choice for palliative RT for SBM. Strongly hypofractionated RT regimes may be advisable for most elderly patients considering the overall poor prognosis in order to reduce hospitalization times.
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Osteólisis/radioterapia , Cuidados Paliativos , Neoplasias de la Columna Vertebral/radioterapia , Neoplasias de la Columna Vertebral/secundario , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Fracturas Espontáneas/radioterapia , Alemania , Humanos , Masculino , Osteólisis/mortalidad , Pronóstico , Estudios Retrospectivos , Fracturas de la Columna Vertebral/radioterapia , Neoplasias de la Columna Vertebral/mortalidad , Análisis de SupervivenciaRESUMEN
Background and purpose: To evaluate the tolerability and outcomes of chemoradiation in elderly patients with locally advanced esophageal squamous cell carcinoma (ESCC). Materials and methods: This multi-center retrospective analysis included 161 patients with SCC of the esophagus with a median age of 73 years (range 65-89 years) treated with definitive or neoadjuvant (chemo)radiotherapy between 2010 and 2019 at 3 large comprehensive cancer centers in Germany. Locoregional control (LRC), progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), and treatment-associated toxicities were analyzed, and parameters determining patient outcomes and treatment tolerance were assessed. Results: The delivery of radiotherapy without dose reduction was possible in 149 patients (93%). In 134 patients (83%), concomitant chemotherapy was initially prescribed; however, during the course of therapy, 41% of these patients (n = 55) required chemotherapy de-escalation due to treatment-related toxicities. Fifty-two patients (32%) experienced higher-grade acute toxicities, and 22 patients (14%) higher-grade late toxicities. The 2-year LRC, DMFS, PFS, and OS rates amounted to 67.5%, 33.8%, 31.4%, and 40.4%, respectively. Upon multivariate analysis, full-dose concomitant chemotherapy (vs. no or modified chemotherapy) was associated with significantly better DMFS (p=0.005), PFS (p=0.005) and OS (p=0.001). Furthermore, neoadjuvant chemoradiotherapy followed by tumor resection (vs. definitive chemoradiotherapy or definitive radiotherapy alone) significantly improved PFS (p=0.043) and OS (p=0.049). We could not identify any clinico-pathological factor that was significantly associated with LRC. Furthermore, definitive (chemo)radiotherapy, brachytherapy boost and stent implantation were significantly associated with higher-grade acute toxicities (p<0.001, p=0.002 and p=0.04, respectively). The incidence of higher-grade late toxicities was also significantly associated with the choice of therapy, with a higher risk for late toxicities when treatment was switched from neoadjuvant to definitive (chemo)radiotherapy compared to primary definitive (chemo)radiotherapy (p<0.001). Conclusions: Chemoradiation with full-dose and unmodified concurrent chemotherapy has a favorable prognostic impact in elderly ESCC patients; however, about half of the analyzed patients required omission or adjustment of chemotherapy due to comorbidities or toxicities. Therefore, the identification of potential predictive factors for safe administration of concurrent chemotherapy in elderly ESCC patients requires further exploration to optimize treatment in this vulnerable patient cohort.
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BACKGROUND: Carcinomas of the lips are a relatively common malignancy of the head and neck region, accounting for roughly one quarter of all oral cavity cancers. Compared to other oral cancer sites, this location has a favorable prognosis, with 5-year survival rates between 85% and 95%. This study summarizes our institutional experience in utilizing postoperative radiation for patients with squamous cell carcinoma of the upper and/or lower lip following incomplete surgical resection or positive lymph node involvement with extracapsular extension. METHODS: We retrospectively reviewed the medical records of all patients at the University Hospital of Heidelberg between 2005 and 2018 treated with postoperative radiotherapy of the upper and lower lip. Nineteen patients were identified with a median age at diagnosis of 67 years (range, 41-95 years), with 58% male and 42% female patients. Fourteen patients (73.7%) underwent neck dissection, with 5 (35.7%) found to have extracapsular extension (ECE) and positive resection margin (R1/2), 2 (14.3%) only ECE, and 7 (50.0%) with only R1/2. All patients received a median cumulative dose of 66.0 Gy (range, 60.0-70.0 Gy) in a median of 2.0 Gy per fraction (range, 1.8-2.2 Gy). RESULTS: Median follow-up was 5.2 years. The median progression-free survival (PFS) was 3.9 years (range, 0.2-12.4 years), local disease-free survival (LDFS) was 4 years (range, 1-12 years) and overall survival (OS) was 5.2 years (range, 0.2-12.4 years). The 5-year Kaplan-Meier estimates for OS, PFS, and LDFS were 61.4%, 85.7%, and 100.0%, respectively. At last follow-up, 13 patients (68.4%) were still alive. Although no patient developed locoregional relapse, two patients developed distant relapse at a median of 15 months after radiotherapy. There was a statistically significant improvement in OS in patients treated with higher radiotherapy doses (>60.0 Gy, p = 0.044) compared to lower radiotherapy doses. PFS was significantly improved among patients who had N0 disease, with a negative resection margin, without ECE, and who were treated with intensity-modulated radiotherapy to doses >60.0 Gy. No grade 3/4 toxicity was detected; the most common grade 1/2 toxicities included dermatitis (n = 11, 57.9%), oral mucositis (n = 8, 42.1%), and dysphagia (n = 8, 42.1%). CONCLUSION: Our results demonstrate excellent local control and OS with acceptable toxicity when utilizing postoperative radiotherapy in patients with squamous cell carcinoma of the upper and lower lip, despite unfavorable characteristics (advanced T or N stage and/or ECE).
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Terapia Combinada , Femenino , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Labio/patología , Masculino , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Dosificación Radioterapéutica , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: To compare two validated spinal instability scores regarding the stabilizing effects and skeletal-related events (SREs) of palliative radiotherapy (RT) in patients with spinal bone metastases (SBM). MATERIALS AND METHODS: Two hundred eighty-two osteolytic SBM of lung or breast cancer patients were analyzed for stability before and following RT based on the Spinal Instability Neoplastic Score (SINS) or the Taneichi score. Score concordance was quantified by absolute agreement and Cohen's kappa coefficient. SREs were defined as fractures or local progression after RT. OS was quantified as the time between the start of RT and death from any cause. RESULTS: At 3 and 6 months after RT, 35 and 50% of initially unstable SBM were re-stabilized according to SINS in patients still alive. Corresponding Taneichi score-based stabilization proportions were 25 and 46%, respectively. Comparison of both stability scores showed high absolute agreement for all time-points (range 71-78%, kappa range 0.35-0.44). SRE occurred more frequently in initially unstable SBM compared to stable SBM according to SINS (14 vs. 5%), but no such association could be shown for the Taneichi-based instability criterion. Poor general condition of patients was negatively associated with SINS-measured re-stabilization after 6 months, but no predictive factor for re-stabilization could be found for the Taneichi score. CONCLUSIONS: Despite the relatively high agreement between both stabilization scores, the SINS should be considered the standard for future studies on the stabilization effects of RT in SBM.
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BACKGROUND: Radiotherapy (RT) is an established, potentially curative treatment option for all risk constellations of localized prostate cancer (PCA). Androgen deprivation therapy (ADT) and dose-escalated RT can further improve outcome in high-risk (HR) PCA. In recent years, shorter RT schedules based on hypofractionated RT have shown equal outcome. Stereotactic body radiotherapy (SBRT) is a highly conformal RT technique enabling ultra-hypofractionation which has been shown to be safe and efficient in patients with low- and intermediate-risk PCA. There is a paucity of data on the role of SBRT in HR PCA. In particular, the need for pelvic elective nodal irradiation (ENI) needs to be addressed. Therefore, we conducted a systematic review to analyze the available data on observed toxicities, ADT prescription practice, and oncological outcome to shed more light on the value of SBRT in HR PCA. METHODS: We searched the PubMed and Embase electronic databases for the terms "prostate cancer" AND "stereotactic" AND "radiotherapy" in June 2020. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. RESULTS: After a rigorous selection process, we identified 18 individual studies meeting all selection criteria for further analyses. Five additional studies were included because their content was judged as relevant. Three trials have reported on prostate SBRT including pelvic nodes; 2 with ENI and 1 with positive pelvic nodes only. The remaining studies investigated SBRT of the prostate only. Grade 2+ acute genitourinary (GU) toxicity was between 12% and 46.7% in the studies investigating pelvic nodes irradiation and ranged from 0% to 89% in the prostate only studies. Grade 2+ chronic GU toxicity was between 7% and 60% vs. 2% and 56.7%. Acute gastrointestinal (GI) grade 2+ toxicity was between 0% to 4% and 0% to 18% for studies with and without pelvic nodes irradiation, respectively. Chronic GI grade 2+ toxicity rates were between 4% and 50.1% vs. 0% and 40%. SBRT of prostate and positive pelvic nodes only showed similar toxicity rates as SBRT for the prostate only. Among the trials that reported on ADT use, the majority of HR PCA patients underwent ADT for at least 2 months; mostly neoadjuvant and concurrent. Biochemical control rates ranged from 82% to 100% after 2 years and 56% to 100% after 3 years. Only a few studies reported longer follow-up data. CONCLUSION: At this point, SBRT with or without pelvic ENI cannot be considered the standard of care in HR PCA, due to missing level 1 evidence. Treatment may be offered to selected patients at specialized centers with access to high-precision RT. While concomitant ADT is the current standard of care, the necessary duration of ADT in combination with SBRT remains unclear. Ideally, all eligible patients should be enrolled in clinical trials.
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BACKGROUND AND PURPOSE: To evaluate oncological outcomes and treatment-related toxicities of elderly salivary gland cancer patients undergoing (chemo)radiotherapy. MATERIAL AND METHODS: Local/locoregional control (LRC), progression-free survival (PFS) and overall survival (OS) of elderly patients ≥ 65 years with primary salivary gland cancers undergoing (chemo)radiotherapy between 2005 and 2020 at three tertiary cancer centers were calculated. The impact of clinicopathological and treatment parameters on outcomes were analyzed, and acute and chronic toxicities were quantified. RESULTS: 288 elderly salivary gland cancer patients were included in this multicenter analysis, and their median LRC, PFS and OS amounted to 113, 39 and 75 months, respectively. Age, performance status, comorbidities, definitive vs. adjuvant (chemo)radiotherapy as well as locally/locoregionally advanced cancers and distant metastases correlated with reduced outcomes in elderly salivary gland patients. Patients receiving dose-escalated radiotherapy (total doses > 70 GyEQD2) with carbon ion boost radiation resulted in improved LRC, but no improvements in PFS or OS. Concomitant chemoradiotherapy did not improve treatment outcomes in elderly salivary gland carcinoma patients. Radiotherapy of elderly salivary gland cancer patients resulted in moderate higher-grade toxicities despite dose escalation with 70 (24.3%) and 48 patients (16.7%) experiencing acute and chronic grade 3 toxicities, respectively. No grade 4/5 toxicities were observed in this patient cohort. CONCLUSION: Data from the largest multicenter analysis of elderly salivary gland cancer patients undergoing (chemo)radiotherapy demonstrate favorable LRC and tolerable toxicity rates. Decision-making for these vulnerable patients should be based on patient performance rather than chronological patient age.
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Neoplasias de las Glándulas Salivales , Anciano , Quimioradioterapia , Humanos , Supervivencia sin Progresión , Estudios Retrospectivos , Neoplasias de las Glándulas Salivales/radioterapia , Resultado del TratamientoRESUMEN
This single-center, single-arm trial investigates the feasibility of a psycho-oncological care program, which aims to reduce psychological distress and improve compliance with radiotherapy with mask fixation in patients with head and neck cancer or brain malignancies. The care program comprised (1) a screening/needs assessment and (2) the provision of a psycho-oncological intervention using imaginative stabilization techniques for distressed patients (distress due to anxiety ≥5) or in a case of subjective interest in the psycho-oncological intervention. Another allocation path to the intervention was directly through the radiation oncologist in charge who classified the patient as: in need of support to tolerate the immobilization device. Of a total of 1,020 screened patients, 257 (25.2%) patients indicated a distress ≥5 and 141 (13.8%) patients reported panic attacks. 25% of the patients reported a subjective interest in psycho-oncological support. A total of 35 patients received the psycho-oncological intervention, of which 74% were assigned by radiation oncologists. In this small patient cohort, no significant pre-post effects in terms of depression, anxiety, distress, and quality of life (mental and physical component scores) could be detected. Our results indicate a good feasibility (interdisciplinary workflow and cooperation, allocation by physicians in charge) of the psycho-oncological care program for this cohort of patients before radiotherapy with mask fixation. The screening results underline the high psychological distress and demand for psycho-oncological support. However, since the utilization of our intervention was low, future studies should reduce the barriers and improve compliance to psycho-oncological services by these patients.Clinical Trial Registration: https://www.drks.de/drks_web/setLocale_EN.do #DRKS00013493.
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BACKGROUND: This study aimed to contrast four different irradiation methods for pediatric medulloblastoma tumors in a dosimetric comparison regarding planning target volume (PTV) coverage and sparing of organs at risk (OARs). METHODS: In sum 24 treatment plans for 6 pediatric patients were realized. Besides the clinical standard of a 3D-conformal radiotherapy (3D-CRT) treatment plan taken as a reference, volumetric modulated arc therapy (VMAT) treatment plans ("VMAT_AVD" vs. "noAVD" vs. "FullArc") were optimized and calculated for each patient. For the thoracic and abdominal region, the short partial-arc VMAT_AVD technique uses an arc setup with reduced arc-length by 100°, using posterior and lateral beam entries. The noAVD uses a half 180° (posterior to lateral directions) and the FullArc uses a full 360° arc setup arrangement. The prescription dose was set to 35.2 Gy. RESULTS: We identified a more conformal dose coverage for PTVs and a better sparing of OARs with used VMAT methods. For VMAT_AVD mean dose reductions in organs at risk can be realized, from 16 to 6.6 Gy, from 27.1 to 8.7 Gy and from 8.0 to 1.9 Gy for the heart, the thyroid and the gonads respectively, compared to the 3D-CRT treatment method. In addition we have found out a superiority of VMAT_AVD compared to the noAVD and FullArc trials with lower exposure to low-dose radiation to the lungs and breasts. CONCLUSIONS: With the short partial-arc VMAT_AVD technique, dose exposures to radiosensitive OARS like the heart, the thyroid or the gonads can be reduced and therefore, maybe the occurrence of late sequelae is less likely. Furthermore the PTV conformity is increased. The advantages of the VMAT_AVD have to be weighed against the potentially risks induced by an increased low dose exposure compared to the 3D-CRT method.
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Neoplasias Cerebelosas/radioterapia , Irradiación Craneoespinal , Meduloblastoma/radioterapia , Radioterapia de Intensidad Modulada/métodos , Adolescente , Niño , Preescolar , Humanos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
BACKGROUND: This study aimed to analyze the oncological long-term results and late toxicity of carbon ion-based radiotherapy (RT) of patients with sacral chordoma and to identify potential prognostic factors for local control (LC) and overall survival (OS). METHODS: A total of 68 patients with sacral chordoma treated at the Heidelberg Ion Beam Therapy Center were included in this study. Of these 52 patients (77%) received a primary RT and 16 patients (23%) received a RT in a recurrent situation. All patients were treated with carbon ion RT (CIRT), either in combination with photons (n = 22; 32%) or as a monotherapy (n = 46; 68%), with a median radiation dose of 66 Gy RBE (range 60-74 Gy). In 40 patients (59%), RT was performed in the postoperative situation. Postoperative care included regular MRI scans. Local progression was defined as an enlargement of the maximum tumor diameter by 10% or a new tumor growth within the planning target volume (PTV). LC and OS were determined using the Kaplan-Meier method. Furthermore, the relevance of various prognostic factors for LC and OS was assessed by univariate and multivariate analysis. RESULTS: The median follow-up period was 60 months (range 1.3-97.4 months). The 5-year rates for LC, progression-free survival, metastasis-free survival and OS were 53, 53, 52 and 74%, respectively. Local recurrence was observed in 31 patients (46%), occurring after a median follow-up time of 25 months (range 2.5-73.1 months). Only 10% of local recurrences occurred later than 5 years after RT. Statistical analysis showed that RT in the relapse situation corresponded to inferior LC rates compared to the primary situation, while other factors such as the GTV, radiation dose (EQD2) and treatment approach (CIRT alone vs. CIRT combined with photons) were insignificant. For OS after RT, patient age and PTV size proved to be significant predictors. The incidence of late toxicity ≥ III° according to CTCAE v5.0 was 21%. Sacral insufficiency fractures occurred in 49% of patients (maximum III°: 16%) and were thus by far the most frequent late side effect in our analysis. Radiogenic damage to the peripheral nerves, intestinal tract and skin was observed in only 9% (≥ III°: 5%), 3% (all II°) and 9% (all I°) of patients. CONCLUSION: Our analysis showed only moderate long-term LC rates after carbon ion-based RT, with sacral chordomas having a particularly poor prognosis in the recurrent situation. Therefore, future studies should evaluate the safety and effectiveness of further dose escalation and hypofractionation of RT in sacral chordoma and weight potential benefits of dose escalation against side effects.
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Cordoma/radioterapia , Radioterapia de Iones Pesados/métodos , Recurrencia Local de Neoplasia/radioterapia , Región Sacrococcígea/efectos de la radiación , Adulto , Anciano , Anciano de 80 o más Años , Cordoma/patología , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Región Sacrococcígea/patología , Tasa de Supervivencia , Factores de TiempoRESUMEN
INTRODUTION: We aimed to evaluate treatment outcome of combined radiotherapy (RT) including photon intensity modulated radiotherapy (IMRT) and carbon ion boost for adenoid cystic carcinomas (ACCs) of the major salivary glands, the currently available largest German collective for this cohort. MATERIALS AND METHODS: Overall, 207 patients who were irradiated with combined RT between 2009 and 2019 at Heidelberg University Hospital were analyzed retrospectively for local control (LC), progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier estimates. The majority of patients received postoperative RT (n=176/207, 85%) after previous surgery in large German hospitals mainly Mainz, Freiburg, Mannheim and Heidelberg University Hospitals and 15% received primary RT (n=31/207). RESULTS: After a median follow-up time of 50 months, 84% of the patients were still alive (n=174/207). Disease progression occurred in 32% of the patients (n=66/207) while local recurrence was diagnosed in 12% (n=25/207), and distant relapse in 27% (n=56/207). Estimated 5-year LC, PFS and OS rates were 84%, 56% and 83% for OS, respectively. In multivariate analysis, we could identify two prognostic subgroups: one subgroup resulting in decreased LC, PFS and OS rates and another subgroup having an additional survival disadvantage in PFS and OS. Patients with a macroscopic tumor disease (yes vs. no; p<0.001 for LC, p=0.010 for PFS and p=0.040 for OS) treated in a definitive setting (vs. postoperative setting; p=0.001 for LC, p=0.006 for PFS, p=0.049 for OS) and tumors of upper T stage (T1-4; p=0.004 for LC, p<0.001 for PFS, p<0.001 for OS) showed significantly more local relapses and a decreased PFS and OS. Upper Age (p<0.001 for both PFS and OS), lower Karnofsky Performance Score (<80% vs. ≥80%; p<0.001 for both PFS and OS) and solid histology (vs. non-solid; p=0.049 for PFS and p=0.003 for OS) were in addition associated with worse survival outcome. Toxicity was moderate with 18% late grade 2 and 3 toxicity. CONCLUSIONS: Combined RT results in superior LC rates compared to photon data with moderate toxicity. In multivariate analysis, upper T stage, the existence of a macroscopic tumor before RT and definitive RT setting were identified as major prognostic factors affecting LC negatively.
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PURPOSE: To evaluate the potential of cone-beam-CT (CB-CT) guided adaptive radiotherapy (ART) for locally advanced non-small cell lung cancer (NSCLC) for sparing of surrounding organs-at-risk (OAR). MATERIALS AND METHODS: In 10 patients with locally advanced NSCLC, daily CB-CT imaging was acquired during radio- (n = 4) or radiochemotherapy (n = 6) for simulation of ART. Patients were treated with conventionally fractionated intensity-modulated radiotherapy (IMRT) with total doses of 60-66 Gy (pPlan) (311 fraction CB-CTs). OAR were segmented on every daily CB-CT and the tumor volumes were modified weekly depending on tumor changes. Doses actually delivered were recalculated on daily images (dPlan), and voxel-wise dose accumulation was performed using a deformable registration algorithm. For simulation of ART, treatment plans were adapted using the new contours and re-optimized weekly (aPlan). RESULTS: CB-CT showed continuous tumor regression of 1.1 ± 0.4% per day, leading to a residual gross tumor volume (GTV) of 65.3 ± 13.4% after 6 weeks of radiotherapy (p = 0.005). Corresponding PTVs decreased to 83.7 ± 7.8% (p = 0.005). In the actually delivered plans (dPlan), both conformity (p = 0.005) and homogeneity (p = 0.059) indices were impaired compared to the initial plans (pPlan). This resulted in higher actual lung doses than planned: V20Gy was 34.6 ± 6.8% instead of 32.8 ± 4.9% (p = 0.066), mean lung dose was 19.0 ± 3.1 Gy instead of 17.9 ± 2.5 Gy (p = 0.013). The generalized equivalent uniform dose (gEUD) of the lung was 18.9 ± 3.1 Gy instead of 17.8 ± 2.5 Gy (p = 0.013), leading to an increased lung normal tissue complication probability (NTCP) of 15.2 ± 13.9% instead of 9.6 ± 7.3% (p = 0.017). Weekly plan adaptation enabled decreased lung V20Gy of 31.6 ± 6.2% (-3.0%, p = 0.007), decreased mean lung dose of 17.7 ± 2.9 Gy (-1.3 Gy, p = 0.005), and decreased lung gEUD of 17.6 ± 2.9 Gy (-1.3 Gy, p = 0.005). Thus, resulting lung NTCP was reduced to 10.0 ± 9.5% (-5.2%, p = 0.005). Target volume coverage represented by conformity and homogeneity indices could be improved by weekly plan adaptation (CI: p = 0.007, HI: p = 0.114) and reached levels of the initial plan (CI: p = 0.721, HI: p = 0.333). CONCLUSION: IGRT with CB-CT detects continuous GTV and PTV changes. CB-CT-guided ART for locally advanced NSCLC is feasible and enables superior sparing of healthy lung at high levels of plan conformity.
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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 Inmunológicos/uso terapéutico , Carcinoma Adenoide Quístico/terapia , Cetuximab/uso terapéutico , Quimioradioterapia/métodos , Neoplasias de Cabeza y Cuello/terapia , Radioterapia de Iones Pesados , Radioterapia de Intensidad Modulada , Antineoplásicos Inmunológicos/administración & dosificación , Carcinoma Adenoide Quístico/patología , Cetuximab/administración & dosificación , Quimioradioterapia/efectos adversos , Terapia Combinada/métodos , Trastornos de Deglución/etiología , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Esquema de Medicación , Estudios de Factibilidad , Femenino , Neoplasias de Cabeza y Cuello/patología , Radioterapia de Iones Pesados/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Radiodermatitis/etiología , Radioterapia de Intensidad Modulada/efectos adversos , Efectividad Biológica Relativa , Xerostomía/etiologíaRESUMEN
Purpose/Objective: Oligometastatic disease (OMD) and oligoprogressive disease (OPD) describe tumor states with a limited metastasization. In contrast to other disease states, treatment of OMD or OPD has not yet become common for breast cancer. We sought to understand the outcomes and toxicities of this treatment paradigm. Material/Methods: We retrospectively analyzed female breast cancer patients with OMD (≤3 metastases) or OPD (1 progressive lesion) who received stereotactic body radiotherapy (SBRT) for their respective extracranial metastatic lesions between 01/2002 and 07/2019. Survival analysis was performed using the Kaplan-Meier method with log-rank test being used for evaluation of significance. Cox regression was used to detect prognostic outcome factors. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v. 5.0). Results: Forty-six patients (70% OMD; 30% OPD) with 58 lesions met criteria for inclusion. The majority of treatments (34 out of 58; 58.6%) were delivered from 2017 to 2018. Treatment sites were bone, liver, lung [n = 19 (33%) for each site], and adrenal gland [n = 1 (1%)]. Median biologically effective dose (BED at α/ß = 10) was 81.6 Gy (range: 45-112.5 Gy) and median planning target volume was 36.60 mL (range: 3.76-311.00 mL). At 2 years, local control (LC) was 89%, distant control (DC) was 44%, progression free survival (PFS) was 17% and overall survival (OS) was 62%. Multivariate analysis identified the diagnosis of a solitary metastasis as an independent prognostic factor for superior DC (HR = 0.186, CI [0.055; 0.626], p = 0.007) and PFS (HR = 0.363, CI [0.152; 0.863], p = 0.022). OS was independently inferior for patients treated at a higher age (HR = 5.788, CI [1.077; 31.119] p = 0.041). Nine (15.5%) grade I° and one (1.7%) grade II° toxicities were recorded, with no grade III° or higher toxicities. Conclusion: Extracranial SBRT in breast cancer patients with OMD or OPD was well-tolerated with excellent LC. SBRT should especially be offered to younger OMD and OPD breast cancer patients with only one metastasis. The increase in utilization since 2017 points toward a growing acceptance of SBRT for OMD and OPD in breast cancer.
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BACKGROUND AND AIM: The primary aim of our study was to evaluate percutaneous endoscopic gastrostomy (PEG) tube placement depending on body weight and body mass index in patients undergoing radiotherapy (RT) for head and neck cancer (HNC). A secondary aim was to evaluate the course of weight change following PEG placement. METHODS: We retrospectively reviewed the medical records of 186 patients with HNC undergoing radiotherapy (RT) or chemoradiotherapy (CRT) at our institution between January 2010 and August 2017. Initial weight and nutritional intake were analyzed prior to RT initiation and then followed throughout treatment until completion. Based on these data, the indication of PEG placement was determined. Medical records were also reviewed to analyze PEG-related acute toxicities. RESULTS: A total of 186 patients met inclusion criteria. Patients were most commonly male (n=123, 66.1%) with squamous cell carcinoma (n=164, 88.2%). Patients who had dysphagia prior to treatment initiation as well as patients with a BMI <18.5 kg/m2 needed PEG placement earlier during the treatment course. Low-grade toxicities related to PEG insertion were observed in 10.7% patients, with peristomal pain and redness adjacent to the PEG tube insertion site being most common. High-grade toxicities, such as peritonitis and organ injury, were found in 4.9% of patients. CONCLUSION: Underweight patients and those with preexisting dysphagia should be closely screened during RT for weight loss and decreased oral intake. For weight loss greater than 4.5% during the treatment of HNC, early PEG-tube placement should be considered. Further prospective studies are needed to confirm these findings, and delineate a scoring system for timing of PEG use (prophylactic vs reactive) as well as assess the quality of life in patients with HNC who receive PEG placement.
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BACKGROUND: Fatigue is one of the most common and distressing side-effects of breast cancer radiotherapy. According to current guidelines, accelerated partial breast irradiation (APBI) may be considered as an alternative treatment option for women with early-stage low-risk breast cancer. One method for APBI is single-dose intraoperative radiotherapy (IORT) applied directly to the tumor bed during breast conserving surgery (BCS). The COSMOPOLITAN trial therefore aims to analyze the intensity of fatigue following single-shot IORT with electrons (IOERT) compared to conventional hypofractionated whole breast irradiation (WBI) in low risk early breast cancer patients. METHODS: This trial is conducted as a multicenter, prospective, randomized, two-arm phase II study comparing the intensity of fatigue in early-stage breast cancer (cT1cN0cM0, tumor size < 2,5 cm, ER pos. Her2neu neg., age > 50 years) treated either with WBI or APBI after BCS. Secondary outcomes investigated are tumor control, overall survival (OS), disease-free survival (DFS), acute and chronic toxicity, quality of life (QoL) and cosmesis. A total of 202 patients will be randomized into two arms: Patients in arm A will receive WBI (40.05 Gy, 15 fractions) after surgical resection, while patients in arm B will receive IOERT (21 Gy to the 90%-isodose) during BCS. Fatigue will be assessed 12 weeks post surgery with the help of the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale. DISCUSSION: The present trial aims to evaluate treatment response to compare single-shot intraoperative electron APBI to conventional WBI following BCS in early-stage low risk breast cancer patients. Fatigue is selected as the primary, patient-reported endpoint due its major clinical relevance. TRIAL REGISTRATION: The study is prospectively registered on February 12th, 2019: Clinicaltrials.gov, NCT03838419. "Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer (COSMOPOLITAN)". STUDY STATUS: Ongoing study. Start of recruitment was December 2019.
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Neoplasias de la Mama/radioterapia , Fatiga/etiología , Radioterapia Adyuvante/efectos adversos , Radioterapia Adyuvante/métodos , Anciano , Neoplasias de la Mama/cirugía , Fatiga/epidemiología , Femenino , Humanos , Periodo Intraoperatorio , Persona de Mediana Edad , Hipofraccionamiento de la Dosis de Radiación , Radioterapia de Alta Energía/métodos , Radioterapia de Intensidad Modulada/métodos , Proyectos de InvestigaciónRESUMEN
This retrospective multi-center analysis aimed to assess the clinical response and stabilizing effects of palliative radiotherapy (RT) for spinal bone metastases (SBM) in head and neck cancer (HNC), and to establish potential predictive factors for stability and overall survival (OS). Patients included in this analysis were treated at the University Hospitals of Mainz, Freiburg, and Heidelberg between 2001 and 2019. Clinical information was taken from the medical records. The stability of affected vertebral bodies was assessed according to the validated spine instability neoplastic score (SINS) based on CT-imaging before RT, as well as 3 and 6 months after RT. OS was quantified as the time between the start of palliative RT and death from any cause or last follow-up. Potential predictive factors for stability and OS were analyzed using generalized estimating equations and Cox regression for time-varying covariates to take into account multiple observations per patient. The mean follow-up time of 66 included patients after the first palliative RT was 8.1 months (range 0.3-85.0 months). The majority of patients (70%; n = 46) had squamous cell carcinomas (SCC) originating from the pharynx, larynx and oral cavity, while most of the remaining patients (26%; n = 17) suffered from salivary glands tumors. A total of 95 target volumes including 178 SBM were evaluated that received a total of 81 irradiation series. In patients with more than one metastasis per irradiated region, only the most critical bone metastasis was analyzed according to the SINS system. Prior to RT, pain and neurologic deficits were present in 76% (n = 72) and 22% (n = 21) of irradiated lesions, respectively, and 68% of the irradiated lesions (n = 65) were assessed as unstable or potentially unstable prior to RT. SBM-related pain symptoms and neurologic deficits responded to RT in 63% and 47% of the treated lesions, respectively. Among patients still alive at 3 and 6 months after RT with potentially unstable or unstable SBM, a shift to a better stability class according to the SINS was observed in 20% and 33% of the irradiated SBM, respectively. Pathological fractures of SBM were frequently detected before the start of irradiation (43%; n = 41), but after RT, new fractures or increasing vertebral body sintering within the irradiated region occurred rarely (8%; n = 8). A pathological fracture before RT was negatively associated with stabilization 6 months after RT (OR 0.1, 95% CI 0.02-0.49, p = 0.004), while a Karnofsky performance score (KPS) ≥ 70% was associated positively with a stabilization effect through irradiation (OR 6.09, 95% CI 1.68-22.05, p = 0.006). Mean OS following first palliative RT was 10.7 months, and the KPS (≥70% vs. <70%) was shown to be a strong predictive factor for OS after RT (HR 0.197, 95% CI 0.11-0.35, p < 0.001). There was no significant difference in OS between patients with SCC and non-SCC. Palliative RT in symptomatic SBM of HNC provides sufficient symptom relief in the majority of patients, while only about one third of initially unstable SBM show re-stabilization after RT. Since patients in our multi-center cohort exhibited very limited OS, fractionation schemes should be determined depending on the patients' performance status.
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Introduction: Data regarding treatment and survival outcome of patients with adenocarcinoma of the head and neck are limited to case reports and case series. As a consequence of lacking evidence, treatment guidelines do not exist. We aimed to analyze the effect of a bimodal irradiation regime with intensity modulated radiotherapy (IMRT) and carbon ion boost on local control (LC) and survival in adenocarcinoma patients for a large patient collective. Materials and Methods: Patient records of eighty consecutive patients treated between 2009 and 2018 were analyzed retrospectively and Kaplan-Meier estimates for LC, overall survival (OS) and progression-free survival (PFS) were compared among patients with salivary gland adenocarcinoma (SGAC), salivary duct adenocarcinoma (SDAC), and intestinal-type adenocarcinoma (ITAC) according to the World Health Organization (WHO). Prognostic factors were identified using the log-rank test and cox-regression modeling. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE). Results: Median follow-up was 41 months. The 3-year and estimated 5-year Kaplan-Meier rates for all patients were 83 and 75% for LC, 74 and 50% for OS and 60 and 53% for PFS, respectively. While bimodal RT for ITAC resulted in a significantly decreased 3-year LC rate of 50 vs. 93% for each SGAC and SDAC (p < 0.01), no statistical significant survival differences could be identified across the three groups regarding OS (p = 0.08) and PFS (p = 0.063). 3-year OS was 88% for SGAC, 78% for SDAC and 67% for ITAC and 3-year PFS was 72% for SGAC, 53% for SDAC and 44% for ITAC, respectively. Nevertheless, in subgroup analysis, OS for ITAC was significantly worse compared to SGAC (p = 0.024). In multivariate analysis, bilateral tumor side (vs. unilateral) solely could be identified as independent negative prognostic factor for LC (p < 0.01). Treatment was well-tolerated with 21% acute (n = 17) and 25% (n = 20) late grade ≥3 toxicities. Conclusion: Radiotherapy including active raster-scanning carbon ion boost for relatively radio resistant adenocarcinomas of the head and neck resulted in favorable survival outcome for salivary gland and salivary duct adenocarcinomas with moderate toxicity. However, local control and prognosis for bilateral intestinal-type adenocarcinomas (ITAC) seem to remain low even after dose-escalation.