RESUMEN
BACKGROUND: Chordomas and chondrosarcomas of the skull base are rare, slowly growing malignant bone neoplasms. Despite their radioresistant properties, proton therapy has been successfully used as an adjunct to resection or as a definitive treatment. Herewith, we present our experience with robustly optimized intensity-modulated proton therapy (IMPT) and related toxicities in skull base chordoma and chondrosarcoma patients treated at HollandPTC, Delft, the Netherlands. METHODS: Clinical data, treatment plans, and acute toxicities of patients treated between July 2019 and August 2021 were reviewed. CT and 3.0T MRI scans for treatment planning were performed in supine position in a thermoplastic mold. In total, 21 dose optimization and 28 dose evaluation scenarios were simulated. Acute toxicity was scored weekly before and during the treatment according to the CTCAE v4.0. Median follow-up was 35 months (range 12-36 months). RESULTS: Overall, 9 chordoma and 3 chondrosarcoma patients with 1-3 resections prior to IMPT were included; 4 patients had titanium implants. Brainstem core and surface and spinal cord core and surface were used for nominal plan robust optimization in 11, 10, 8, and 7 patients, respectively. Middle ear inflammation, dry mouth, radiation dermatitis, taste disorder, and/or alopecia of grades 1-3 were noted at the end of treatment among 6 patients without similar complaints at inclusion; symptoms disappeared 3 months following the treatment. CONCLUSION: Robustly optimized IMPT is clinically feasible as a postoperative treatment for skull base chordoma and chondrosarcoma patients. We observed acceptable early toxicities (grade 1-3) that disappeared within the first 3 months after irradiation.
RESUMEN
PURPOSE: Morphological magnetic resonance (MR) and computed tomography (CT) features are used in combination with histology for diagnosis and treatment selection of primary bone neoplasms. Isolated functional MRI parameters have shown potential in diagnosis. Our goal is to facilitate diagnosis of primary bone neoplasms of the skull base, mobile spine and sacrum, by a comprehensive approach, combining morphological and functional imaging parameters. MATERIALS AND METHODS: Pre-treatment MR of 80 patients with histologically proven diagnosis of a primary bone neoplasm of the skull base, mobile spine and sacrum were retrospectively analyzed for morphological and functional MRI parameters. Functional parameters were measured in 4 circular regions of interest per tumor placed on non-adjacent scan slices. Differences in values of functional parameters between different histologies were analyzed with Dunn's test. RESULTS: Chordomas were the predominant histology (60.0%). Most neoplasms (80.0%) originated in the midline and had geographical (78.2%) bone destruction. Amorphous-type calcification (pre-existing bone) was seen only in chordomas. Homogeneous contrast enhancement pattern was seen only in chondrosarcoma and plasmacytoma. Ktrans and Kep were significantly lower in both chordoma, and chondrosarcoma compared to giant cell tumor of the bone (p = 0.006 - 0.011), and plasmacytoma (p = 0.004 - 0.014). Highest diffusion-weighted MRI apparent diffusion coefficient (ADC) values corresponded to chondrosarcoma and were significantly higher to those of chordoma (p = 0.008). CONCLUSION: We identified the most discriminating morphological parameters and added functional MR parameters based on histopathological features that are useful in making a confident diagnosis of primary bone neoplasms in the skull base, mobile spine and sacrum.
RESUMEN
BACKGROUND: Thoracic radiotherapy is one of the corner stones of HL treatment, but it is associated with increased risk of cardiovascular events. As HL is often diagnosed at a young age, long-term follow-up including screening for coronary artery disease (CAD) is recommended. OBJECTIVES: This study aims to evaluate the presence of coronary artery calcium score (CACS) in relation to cardiovascular events in HL patients treated with thoracic radiotherapy compared to a non-cancer control group. METHODS: Consecutive HL patients who underwent evaluation for asymptomatic CAD with coronary computed tomography angiography > 10 years after thoracic irradiation were included. The study population consisted of 97 HL patients matched to 97 non-cancer patients on gender, age, cardiovascular risk factors, and statin use. RESULTS: Mean age during CT scan in the HL population was 45.5 ± 9.9 and in the non-cancer population 45.5 ± 10.3 years. CACS was elevated (defined as >0) in 49 (50.5%) HL patients and 30 (30.9%) control patients. HL survivors had an odds ratio of 2.28 [95% CI: 1.22-4.28] for having a CACS > 0 compared to the matched population (p = 0.006). Prevalence of CACS > 90th percentile differed significantly: 17.1% in HL survivors vs. 4.6% in the matched population (p = 0.009). Non-obstructive coronary artery stenosis was more prevalent in the HL population than in the control population (45.7% vs. 28.4%, respectively, p = 0.01). During follow-up of 8.5 [5.3; 9.9] years, nine HL patients experienced an event including two patients with a CACS of zero. No events occurred in the control population. CONCLUSION: In a matched study population, HL survivors have a higher prevalence of a CACS > 0 and an increased risk of cardiovascular events after thoracic irradiation compared to a matched non-cancer control group.
RESUMEN
Importance: Hodgkin lymphoma (HL) survivors have higher rates of colorectal cancer, which may be associated with subdiaphragmatic radiation therapy and/or alkylating chemotherapy. Although radiation dose-response associations with breast, lung, stomach, pancreatic, and esophageal cancer after HL have been demonstrated, the association of radiation therapy with colorectal cancer remains unclear. Objective: To quantify the rate of colorectal cancer according to radiation dose to the large bowel and procarbazine dose among HL survivors. Design, Setting, and Participants: A nested case-control study examined 5-year HL survivors at 5 hospital centers in the Netherlands. Participants had been diagnosed with HL in 1964 to 2000, when they were 15 to 50 years of age, and were followed for a median of approximately 26 years. Survivors of HL who developed colorectal cancer and survivors who were selected as controls were individually matched on sex, age at HL diagnosis, and date of HL diagnosis. Data were analyzed from July 2021 to October 2022. Exposures: Mean radiation doses to the large bowel were estimated by reconstructing individual radiation therapy treatments on representative computed tomography data sets. Main Outcomes and Measures: Excess rate ratios (ERRs) were modeled to evaluate the excess risk associated with each 1-gray increase in radiation dose, and potential effect modification by procarbazine was explored. Results: The study population included 316 participants (mean [SD] age at HL diagnosis, 33.0 [9.8] years; 221 [69.9%] men), 78 of whom were HL survivors who developed colorectal cancer (cases) and 238 who did not (controls). The median (IQR) interval between HL and colorectal cancer was 25.7 (18.2-31.6) years. Increased colorectal cancer rates were seen for patients who received subdiaphragmatic radiation therapy (rate ratio [RR], 2.4; 95% CI, 1.4-4.1) and those who received more than 8.4 g/m2 procarbazine (RR, 2.5; 95% CI, 1.3-5.0). Overall, colorectal cancer rate increased linearly with mean radiation dose to the whole large bowel and dose to the affected bowel segment. The association between radiation dose and colorectal cancer rate became stronger with increasing procarbazine dose: the ERR per gray to the whole bowel was 3.5% (95% CI, 0.4%-12.6%) for patients who did not receive procarbazine, and increased 1.2-fold (95% CI, 1.1-1.3) for each 1-g/m2 increase in procarbazine dose. Conclusions and Relevance: This nested case-control study of 5-year HL survivors found a dose-response association between radiation therapy and colorectal cancer risk, and modification of this association by procarbazine. These findings may enable individualized colorectal cancer risk estimations, identification of high-risk survivors for subsequent screening, and optimization of treatment strategies.
Asunto(s)
Neoplasias Colorrectales , Enfermedad de Hodgkin , Masculino , Humanos , Niño , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/radioterapia , Procarbazina/efectos adversos , Estudios de Casos y Controles , Sobrevivientes , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/diagnósticoRESUMEN
PURPOSE: Previous efforts to predict absolute risk of treatment-related cardiovascular diseases (CVDs) have mostly focused on childhood cancer survivors. We aimed to develop prediction models for risk of coronary heart disease (CHD) and heart failure (HF) for survivors of adolescent/adult Hodgkin lymphoma (HL). METHODS: For model development, we used a multicenter cohort including 1,433 5-year HL survivors treated between 1965 and 2000 and age 18-50 years at HL diagnosis, with complete data on administered chemotherapy regimens, radiotherapy volumes and doses, and cardiovascular follow-up. Using cause-specific hazard models, covariate-adjusted cumulative incidences for CHD and HF were estimated in the presence of competing risks of death because of other causes than CHD and HF. Age at HL diagnosis, sex, smoking status, radiotherapy, and anthracycline treatment were included as predictors. External validation for the CHD model was performed using a Canadian cohort of 708 HL survivors treated between 1988 and 2004 and age 18-50 years at HL diagnosis. RESULTS: After a median follow-up of 24 years, 341 survivors had developed CHD and 102 had HF. We were able to predict CHD and HF risk at 20 and 30 years after treatment with moderate to good overall calibration and moderate discrimination (areas under the curve: 0.68-0.74), which was confirmed by external validation for the CHD model (areas under the curve: 0.73-0.74). On the basis of our model including prescribed mediastinal radiation dose, 30-year risks ranged from 4% to 78% for CHD and 3% to 46% for HF, depending on risk factors. CONCLUSION: We developed and validated prediction models for CHD and HF with good overall calibration and moderate discrimination. These models can be used to identify HL survivors who might benefit from targeted screening for CVD and early treatment for CVD risk factors.
Asunto(s)
Enfermedades Cardiovasculares , Enfermedad Coronaria , Insuficiencia Cardíaca , Enfermedad de Hodgkin , Adulto , Adolescente , Humanos , Niño , Adulto Joven , Persona de Mediana Edad , Enfermedad de Hodgkin/terapia , Canadá , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/epidemiología , Factores de Riesgo , Enfermedades Cardiovasculares/epidemiología , Enfermedad Coronaria/complicacionesRESUMEN
Studies have shown higher survival rates for patients with Hodgkin lymphoma (HL) treated within clinical trials compared to patients treated outside clinical trials. However, endpoints are often limited to overall survival (OS). In this retrospective cohort study, we investigated the effect of trial participation on OS, the incidence of relapse, second cancer, and cardiovascular disease (CVD). The study population consisted of patients with HL, aged between 14 and 51 years at diagnosis, who started their treatment between 1962 and 2002 at three Dutch cancer centres. Patients were either included in the EORTC Lymphoma Group trials (H1-H9) or treated according to standard guidelines at the time. After adjusting for differences in baseline characteristics, trial participation was associated with longer OS (median OS: 29.4 years [95%CI: 27.0-31.6] for treatment inside trials versus 27.4 years [95%CI: 26.0-28.5] for treatment outside trials, p = .046), a lower incidence of relapse (HR = 0.79, 95%CI: 0.63-0.98, p = .036) and a higher incidence of CVD (HR = 1.49, 95%CI: 1.23-1.79, p < .001). The trial effect for CVD was present only for patients treated before 1983. No evidence of differences in the incidence of second cancer was found. Consequently, essential results from clinical trials should be implemented into standard practice without undue delay.
Asunto(s)
Enfermedades Cardiovasculares , Enfermedad de Hodgkin , Neoplasias Primarias Secundarias , Adolescente , Adulto , Humanos , Persona de Mediana Edad , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Progresión de la Enfermedad , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/epidemiología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Primarias Secundarias/etiología , Estudios Retrospectivos , Web SemánticaRESUMEN
BACKGROUND: Hodgkin lymphoma (HL) survivors treated with chest radiotherapy have an increased risk of breast cancer (BC). Prior HL treatment and associated cardiovascular disease (CVD) risk may limit BC treatment options. It is unknown how treatment adaptations affect BC and CVD outcomes. METHODS: The authors compared 195 BC patients treated with chest/axillary radiotherapy for HL (BC-HL) with 5988 age- and calendar year-matched patients with first primary BC (BC-1). Analyses included cumulative incidence functions and Cox regression models, accounting for tumor characteristics and BC treatment. RESULTS: Compared to BC-1 patients, BC-HL patients received anthracycline-containing chemotherapy (23.7% vs. 43.8%, p < .001) and breast-conserving surgery followed by radiotherapy (7.1% vs. 57.7%, p < .001) less often. BC treatment considerations were reported for 71% of BC-HL patients. BC-HL patients had a significantly higher risk of 15-year overall mortality than BC-1 patients (61% vs. 23%). Furthermore, risks of BC-specific mortality and nonfatal BC events were significantly increased among BC-HL patients, also when accounting for tumor and treatment characteristics (2.2- to 4.5-fold). BC-HL patients with a screen-detected BC had a significantly reduced (61%) BC-specific mortality. One-third of BC-HL patients had CVD at BC-diagnosis, compared to <0.1% of BC-1 patients. Fifteen-year CVD-specific mortality and CVD incidence were significantly higher in BC-HL patients than in BC-1 patients (15.2% vs. 0.4% and 40.4% vs. 6.8%, respectively), which was due to HL treatment rather than BC treatment. CONCLUSIONS: BC-HL patients experience a higher burden of CVD and worse BC outcomes than BC-1 patients. Clinicians should be aware of increased CVD risk when selecting BC treatment for HL survivors. LAY SUMMARY: Patients with breast cancer after Hodgkin lymphoma (BC-HL) may have limited options for BC treatment, due to earlier HL treatment and an associated increased risk of cardiovascular disease (CVD). BC treatment considerations were reported for 71% of BC-HL patients. We examined whether BC-HL patients have a higher risk of CVD or BC events (recurrences/metastases) compared to patients with breast cancer that had no earlier tumors (BC-1). We observed a higher burden of CVD and worse BC outcomes in HL patients compared to BC-1 patients. Clinicians should be aware of increased CVD risk when selecting BC treatment for HL survivors.
Asunto(s)
Neoplasias de la Mama , Enfermedades Cardiovasculares , Enfermedad de Hodgkin , Humanos , Femenino , Enfermedad de Hodgkin/radioterapia , Enfermedad de Hodgkin/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Neoplasias de la Mama/etiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Factores de Riesgo , SobrevivientesRESUMEN
Background: Treatment with thoracic irradiation for classic Hodgkin lymphoma (CHL) leads to improved survival but also increases the risk of cardiovascular events. Left ventricular (LV) dysfunction is usually assessed by echocardiographic left ventricular ejection fraction (LVEF), whereas global longitudinal strain (GLS) can detect early subclinical LV dysfunction. The purpose of this study was to evaluate if conventional echocardiographic parameters and GLS are associated with cardiovascular events during long-term follow-up. Methods: 161 consecutive CHL patients treated with radiotherapy who underwent echocardiography > 10 years after diagnosis were assessed for eligibility. Multivariable cause-specific Cox regression was performed for a composite outcome of cardiac death and cardiovascular events and the competing outcome of noncardiac death. Results: 129 patients (61.2% female, N = 79) with a mean age of 46.3 ± 11.0 years at index visit were eligible for analysis. GLS was impaired in 51 patients (39.5%) and 10.9% had a LVEF of< 50%. The median E/e' was 9.2 [7.2;12.7]. Adjusted for confounders, GLS > −16% showed a significant association with a near four-fold risk of the composite endpoint (HR = 3.95, 95% CI: 1.83−8.52, p < 0.001). LVEF < 50% (HR = 2.99, p = 0.016) and E/e' (HR = 1.16, p < 0.001) also showed a significant relationship with the outcome. None of the aforementioned parameters were associated with the competing outcome. Conclusions: This study shows that LV dysfunction including impaired GLS in CHL survivors is associated with cardiovascular events and cardiac death.
RESUMEN
BACKGROUND: Due to its specific physical characteristics, proton irradiation is especially suited for irradiation of chordomas and chondrosarcoma in the axial skeleton. Robust plan optimization renders the proton beam therapy more predictable upon individual setup errors. Reported experience with the planning and delivery of robustly optimized plans in chordoma and chondrosarcoma of the mobile spine and sacrum, is limited. In this study, we report on the clinical use of robustly optimized, intensity modulated proton beam therapy in these patients. METHODS: We retrospectively reviewed patient, treatment and acute toxicity data of all patients with chordoma and chondrosarcoma of the mobile spine and sacrum, treated between 1 April 2019 and 1 April 2020 at our institute. Anatomy changes during treatment were evaluated by weekly cone-beam CTs (CBCT), supplemented by scheduled control-CTs or ad-hoc control-CTs. Acute toxicity was scored weekly during treatment and at 3 months after therapy according to CTCAE 4.0. RESULTS: 17 chordoma and 3 chondrosarcoma patients were included. Coverage of the high dose clinical target volume was 99.8% (range 56.1-100%) in the nominal and 80.9% (range 14.3-99.6%) in the voxel-wise minimum dose distribution. Treatment plan adaptation was needed in 5 out of 22 (22.7%) plans. Reasons for plan adaptation were either reduced tumor coverage or increased dose to the OAR. CONCLUSIONS: Robustly optimized intensity modulated proton beam therapy for chordoma and chondrosarcoma of the mobile spine is feasible. Plan adaptations due to anatomical changes were required in approximately 23 percent of treatment courses.
Asunto(s)
Neoplasias Óseas , Condrosarcoma , Cordoma , Terapia de Protones , Radioterapia de Intensidad Modulada , Neoplasias Óseas/radioterapia , Condrosarcoma/radioterapia , Cordoma/radioterapia , Estudios de Factibilidad , Humanos , Terapia de Protones/efectos adversos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Estudios Retrospectivos , SacroRESUMEN
BACKGROUND: Thoracic irradiation is one of the cornerstones of Hodgkin lymphoma (HL) treatment, which contributes to high rates of long-term survivorship, but begets a life-long increased risk of heart disease including heart failure. At the cardio-oncology (CO) clinic, persistent sinus tachycardia or elevated resting heart rate (RHR) is frequently observed in these patients. The aim of this study was to evaluate the relation between RHR and left ventricular (LV) dysfunction. METHODS: In 75 HL survivors visiting our CO-clinic echocardiographic evaluation of LV systolic and diastolic function including global longitudinal strain (GLS) was performed to assess subclinical LV dysfunction. RESULTS: Median age of HL diagnosis was 24 [25th-75th percentile: [19], [29]] years with a 17 [12], [25] year interval to CO-clinic visit and 31 patients (41%) were male. Average RHR was 78 ± 14 bpm and 40% of patients (N = 30) had an elevated RHR defined as ≥ 80 bpm. While there was no difference in LV ejection fraction (55.6 ± 4.3 vs. 54.8 ± 6.6; p = 0.543), patients with elevated RHR had abnormal GLS (-15.9% vs. -18.3%, p = 0.045) and higher prevalence of diastolic dysfunction (73.3% vs. 46.7%; p = 0.022). GLS, E/e' ratio and presence of diastolic dysfunction were independently associated with RHR when correcting for age, sex and mantle field irradiation. A significant improvement was observed of the RHR-association model with solely extracardiac confounders when LV-function parameters were added to the model (F-statistic = 6.36, p = 0.003). CONCLUSIONS: This study indicates RHR as a possible marker for subclinical LV-dysfunction in HL survivors.
RESUMEN
BACKGROUND: Few studies have examined the impact of treatment-related morbidity on long-term, cause-specific mortality in Hodgkin lymphoma (HL) patients. METHODS: This multicenter cohort included 4919 HL patients, treated before age 51 years between 1965 and 2000, with a median follow-up of 20.2 years. Standardized mortality ratios, absolute excess mortality (AEM) per 10 000 person-years, and cause-specific cumulative mortality by stage and primary treatment, accounting for competing risks, were calculated. RESULTS: HL patients experienced a 5.1-fold (AEM = 123 excess deaths per 10 000 person-years) higher risk of death due to causes other than HL. This risk remained increased in 40-year survivors (standardized mortality ratio = 5.2, 95% confidence interval [CI] = 4.2 to 6.5, AEM = 619). At age 54 years, HL survivors experienced similar cumulative mortality (20.0%) from causes other than HL to 71-year-old individuals from the general population. Whereas HL mortality statistically significantly decreased over the calendar period (P < .001), solid tumor mortality did not change in the most recent treatment era. Patients treated in 1989-2000 had lower 25-year cardiovascular disease mortality than patients treated in 1965-1976 (4.3% vs 5.7%; subdistribution hazard ratio = 0.65, 95% CI = 0.46 to 0.93). Infectious disease mortality was not only increased after splenectomy but also after spleen irradiation (hazard ratio = 2.81, 95% CI = 1.55 to 5.07). For stage I-II, primary treatment with chemotherapy (CT) alone was associated with statistically significantly higher HL mortality (P < .001 for CT vs radiotherapy [RT]; P = .04 for CT vs RT+CT) but lower 30-year mortality from causes other than HL (15.8%, 95% CI = 9.7% to 23.3%) compared with RT alone (36.9%, 95% CI = 34.0% to 39.8%, P = .001) and RT and CT combined (29.8%, 95% CI = 26.8% to 32.9%, P = .02). CONCLUSIONS: Compared with the general population, HL survivors have a substantially reduced life expectancy. Optimal selection of patients for primary CT is crucial, weighing risks of HL relapse and long-term toxicity.
Asunto(s)
Enfermedad de Hodgkin , Neoplasias Primarias Secundarias , Causas de Muerte , Estudios de Cohortes , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Primarias Secundarias/epidemiología , Factores de Riesgo , SobrevivientesRESUMEN
IMPORTANCE: Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity. OBJECTIVE: To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity. DESIGN, SETTING, AND PARTICIPANTS: The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized controlled trial being conducted in 9 tertiary sarcoma centers in Europe and the US. Participants include adults with nonmetastatic, biopsy-proven and translocation-confirmed myxoid liposarcoma of the extremity or trunk who were enrolled between November 24, 2010, and August 1, 2019. Data analyses, using both per-protocol and intention-to-treat approaches, were conducted from November 24, 2010, to January 31, 2020. INTERVENTIONS: The experimental preoperative radiotherapy regimen consisted of 36 Gy in once-daily 2-Gy fractions, with subsequent definitive surgical resection after an interval of 4 or more weeks. MAIN OUTCOMES AND MEASURES: As a short-term evaluable surrogate for local control, the primary end point was centrally reviewed pathologic treatment response. The experimental regimen was regarded as a success when 70% or more of the resection specimens showed extensive treatment response, defined as 50% or greater of the tumor volume containing treatment effects. Morbidity outcomes consisted of wound complications and late toxic effects. RESULTS: Among the 79 eligible patients, 44 (56%) were men and the median (interquartile range) age was 45 (39-56) years. Two patients did not undergo surgical resection because of intercurrent metastatic disease. Extensive pathological treatment response was observed in 70 of 77 patients (91%; posterior mean, 90.4%; 95% highest probability density interval, 83.8%-96.4%). The local control rate was 100%. The rate of wound complication requiring intervention was 17%, and the rate of grade 2 or higher toxic effects was 14%. CONCLUSIONS AND RELEVANCE: The findings of the DOREMY nonrandomized clinical trial suggest that deintensification of preoperative radiotherapy dose is effective and oncologically safe and is associated with less morbidity than historical controls, although differences in radiotherapy techniques and follow-up should be considered. A 36-Gy dose delivered in once-daily 2-Gy fractions is proposed as a dose-fractionation approach for myxoid liposarcoma, given that phase 3 trials are logistically impossible to execute in rare cancers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02106312.
Asunto(s)
Liposarcoma Mixoide , Cuidados Preoperatorios , Dosis de Radiación , Adulto , Femenino , Humanos , Liposarcoma Mixoide/radioterapia , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Knowledge of imaging findings related to therapy administered to patients with sarcoma is pivotal in selecting appropriate care for these patients. Imaging studies are performed as surveillance in asymptomatic patients or because symptoms, including anxiety, develop. In addition to detection of recurrent disease and assessment of response to therapy, diagnosis of conditions related to therapy that may or may not need treatment has a marked positive impact on quality of life. The purpose of this review is to assist radiologists, nuclear physicians, and others clinicians involved in the diagnosis and treatment of these patients in recognizing imaging findings related to therapy and not to activity of the previously treated sarcoma. Imaging findings are time dependent and often specific in relation to therapy given.
Asunto(s)
Sarcoma/diagnóstico por imagen , Sarcoma/terapia , Humanos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Calidad de VidaRESUMEN
BACKGROUND: Solitary fibrous tumor (SFT) is a rare mesenchymal malignancy. Although surgery is potentially curative, the local relapse risk is high after marginal resections. Given the lack of prospective clinical trial data, the objective of the current study was to better define the role of perioperative radiotherapy (RT) in various SFT presentations by location. METHODS: This was retrospective study performed across 7 sarcoma centers. Clinical information was retrieved from all adult patients with extrameningeal, primary, localized SFT who were treated between 1990 and 2018 with surgery alone (S) compared with those who also received perioperative RT (S+RT). Differences in treatment characteristics between subgroups were tested using analysis of variance statistics and propensity score matching. Local control and overall survival rates were calculated from the start of treatment until progression or death from any cause. RESULTS: Of all 549 patients, 428 (78%) underwent S, and 121 (22%) underwent S+RT. The median follow-up was 52 months. After correction for mitotic count and surgical margins, S+RT was significantly associated with a lower risk of local progression (hazard ratio, 0.19: P = .029), an observation further confirmed by propensity score matching (P = .012); however, this association did not translate into an overall survival benefit. CONCLUSIONS: The results from this retrospective study investigating perioperative RT in patients with primary extrameningeal SFT suggest that combining RT with surgery in the management of this patient population is significantly associated with a reduced risk of local failures, especially in patients who have less favorable resection margins and in those who have tumors with a high mitotic count.
Asunto(s)
Tumores Fibrosos Solitarios/radioterapia , Tumores Fibrosos Solitarios/cirugía , Análisis de Varianza , Terapia Combinada/estadística & datos numéricos , Progresión de la Enfermedad , Extremidades , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Masculino , Persona de Mediana Edad , Índice Mitótico , Supervivencia sin Progresión , Puntaje de Propensión , Neoplasias Retroperitoneales/mortalidad , Neoplasias Retroperitoneales/radioterapia , Neoplasias Retroperitoneales/cirugía , Estudios Retrospectivos , Tumor Fibroso Solitario Pleural/mortalidad , Tumor Fibroso Solitario Pleural/radioterapia , Tumor Fibroso Solitario Pleural/cirugía , Tumores Fibrosos Solitarios/mortalidad , Tasa de Supervivencia , TorsoRESUMEN
Purpose: Chondrosarcomas are a group of cartilaginous malignant neoplasms characterized by the deposition of chondrogenic extracellular matrix. Surgical resection is currently the only curative treatment option, due to their high resistance to conventional chemotherapy and radiotherapy. Novel therapeutic treatment options may improve outcome. Predominantly used cell line monolayer in vitro models lack in vivo complexity, such as the presence of extracellular matrix, and differing oxygen access. Hence, we aimed to improve pre-clinical chondrosarcoma research by developing an alginate-based 3D cell culture model. Method: An alginate scaffold was applied to generate spheroids of three chondrosarcoma cell lines (CH2879, JJ012, SW1353). Morphological, histological and immunohistochemical assessment of the spheroids were used to characterize the chondrosarcoma model. Presto blue assay, morphological and immunohistochemical assessment were applied to assess spheroid response to a panel of chemotherapeutics and targeted therapies, which was compared to conventional 2D monolayer models. Synergistic effect of doxorubicin and ABT-737 (Bcl-2 inhibitor) was compared between monolayer and spheroid models using excess over Bliss. A 3D colony formation assay was developed for assessment of radiotherapy response. Results: Chondrosarcoma spheroids produced chondrogenic matrix and remained proliferative after 2 weeks of culture. When treated with chemotherapeutics, the spheroids were more resistant than their monolayer counterparts, in line with animal models and clinical data. Moreover, for sapanisertib (mTOR inhibitor) treatment, a recovery in chondrosarcoma growth, previously observed in mice models, was also observed using long-term treatment. Morphological assessment was useful in the case of YM-155 (survivin inhibitor) treatment where a fraction of the spheroids underwent cell death, however a large fraction remained proliferative and unaffected. Synergy was less pronounced in 3D compared to 2D. A 3D clonogenic assay confirmed increased resistance to radiotherapy in 3D chondrosarcoma spheroids. Conclusion: We demonstrate that the chondrosarcoma alginate spheroid model is more representative of chondrosarcoma in vivo and should be used instead of the monolayer model for therapy testing. Improved selection at in vitro stage of therapeutic testing will increase the amount of information available for experimental design of in vivo animal testing and later, clinical stages. This can potentially lead to increased likelihood of approval and success at clinical trials.
RESUMEN
BACKGROUND: Hodgkin lymphoma (HL) survivors have an increased risk of gastrointestinal (GI) cancer. This study aims to evaluate whether survival of patients who survived HL and developed GI cancer differs from survival of first primary GI cancer patients. METHODS: Overall and cause-specific survival of GI cancer patients in a HL survivor cohort (GI-HL, N = 104, including esophageal, gastric, small intestinal, and colorectal cancer) was compared with survival of a first primary GI cancer patient cohort (GI-1, N = 1025, generated by case matching based on tumor site, gender, age, and year of diagnosis). Cox proportional hazards regression was used for survival analyses. Multivariable analyses were adjusted for GI cancer stage, grade of differentiation, surgery, radiotherapy, and chemotherapy. RESULTS: GI-HL cancers were diagnosed at a median age of 54 years (interquartile range 45-60). No differences in tumor stage or frequency of surgery were found. GI-HL patients less often received radiotherapy (8% vs 23% in GI-1 patients, P < 0.001) and chemotherapy (28% vs 41%, P = 0.01) for their GI tumor. Compared with GI-1 patients, overall and disease-specific survival of GI-HL patients was worse (univariable hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.03-1.65, P = 0.03; and HR 1.29, 95% CI 1.00-1.67, P = 0.049, respectively; multivariable HR 1.33, 95% CI 1.05-1.68, P = 0.02; and HR 1.33, 95% CI 1.03-1.72, P = 0.03, respectively). CONCLUSIONS: Long-term overall and disease-specific survival of GI cancer in HL survivors is worse compared with first primary GI cancer patients. Differences in tumor stage, grade of differentiation, or treatment could not explain this worse survival.
Asunto(s)
Neoplasias Gastrointestinales/mortalidad , Enfermedad de Hodgkin/mortalidad , Adulto , Supervivientes de Cáncer , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Adulto JovenRESUMEN
Female Hodgkin lymphoma (HL) patients treated with chest radiotherapy (RT) have a very high risk of breast cancer. The contribution of genetic factors to this risk is unclear. We therefore examined 211 155 germline single-nucleotide polymorphisms (SNPs) for gene-radiation interaction on breast cancer risk in a case-only analysis including 327 breast cancer patients after chest RT for HL and 4671 first primary breast cancer patients. Nine SNPs showed statistically significant interaction with RT on breast cancer risk (false discovery rate, <20%), of which 1 SNP in the PVT1 oncogene attained the Bonferroni threshold for statistical significance. A polygenic risk score (PRS) composed of these SNPs (RT-interaction-PRS) and a previously published breast cancer PRS (BC-PRS) derived in the general population were evaluated in a case-control analysis comprising the 327 chest-irradiated HL patients with breast cancer and 491 chest-irradiated HL patients without breast cancer. Patients in the highest tertile of the RT-interaction-PRS had a 1.6-fold higher breast cancer risk than those in the lowest tertile. Remarkably, we observed a fourfold increased RT-induced breast cancer risk in the highest compared with the lowest decile of the BC-PRS. On a continuous scale, breast cancer risk increased 1.4-fold per standard deviation of the BC-PRS, similar to the effect size found in the general population. This study demonstrates that genetic factors influence breast cancer risk after chest RT for HL. Given the high absolute breast cancer risk in radiation-exposed women, these results can have important implications for the management of current HL survivors and future patients.
Asunto(s)
Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/radioterapia , Neoplasias Inducidas por Radiación/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/etiología , Supervivientes de Cáncer , Estudios de Casos y Controles , Femenino , Genotipo , Enfermedad de Hodgkin/complicaciones , Humanos , Persona de Mediana Edad , Neoplasias Primarias Secundarias/genética , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Control de Calidad , Dosificación Radioterapéutica , Análisis de Regresión , Riesgo , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: The impact of treatment accuracy on NTCP-based patient selection for proton therapy is currently unknown. This study investigates this impact for oropharyngeal cancer patients. MATERIALS AND METHODS: Data of 78 patients was used to automatically generate treatment plans for a simultaneously integrated boost prescribing 70â¯GyRBE/54.25â¯GyRBE in 35 fractions. IMRT treatment plans were generated with three different margins; intensity modulated proton therapy (IMPT) plans for five different setup and range robustness settings. Four NTCP models were evaluated. Patients were selected for proton therapy if NTCP reduction was ≥10% or ≥5% for grade II or III complications, respectively. RESULTS: The degree of robustness had little impact on patient selection for tube feeding dependence, while the margin had. For other complications the impact of the robustness setting was noticeably higher. For high-precision IMRT (3â¯mm margin) and high-precision IMPT (3â¯mm setup/3% range error), most patients were selected for proton therapy based on problems swallowing solid food (51.3%) followed by tube feeding dependence (37.2%), decreased parotid flow (29.5%), and patient-rated xerostomia (7.7%). CONCLUSIONS: Treatment accuracy has a significant impact on the number of patients selected for proton therapy. Therefore, it cannot be ignored in estimating the number of patients for proton therapy.
Asunto(s)
Neoplasias Orofaríngeas/radioterapia , Selección de Paciente , Terapia de Protones/métodos , Radioterapia de Intensidad Modulada/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia de Protones/efectos adversos , Planificación de la Radioterapia Asistida por Computador/métodos , Xerostomía/etiologíaRESUMEN
BACKGROUND: Young women treated with chest radiation therapy (RT) for Hodgkin lymphoma (HL) experience a strongly increased risk of breast cancer (BC). It is unknown whether endogenous and exogenous gonadal hormones affect RT-associated BC risk. METHODS: We conducted a nested case-control study among female 5-year HL survivors treated before age 41. Hormone exposure and HL treatment data were collected through medical records and questionnaires for 174 BC case patients and 466 control patients. Radiation dose to breast tumor location was estimated based on RT charts, simulation films, and mammography reports. RESULTS: We observed a linear radiation dose-response curve with an adjusted excess odds ratio (EOR) of 6.1%/Gy (95% confidence interval [CI]: 2.1%-15.4%). Women with menopause <30 years (caused by high-dose procarbazine or pelvic RT) had a lower BC risk (OR, 0.13; 95% CI, 0.03-0.51) than did women with menopause ≥50 years. BC risk increased by 6.4% per additional year of post-RT intact ovarian function (P<.001). Among women with early menopause (<45 years), hormone replacement therapy (HRT) use for ≥2 years did not increase BC risk (OR, 0.86; 95% CI, 0.32-2.32), whereas this risk was nonsignificantly increased among women without early menopause (OR, 3.69; 95% CI, 0.97-14.0; P for interaction: .06). Stratification by duration of post-RT intact ovarian function or HRT use did not statistically significantly modify the radiation dose-response curve. CONCLUSIONS: BC risk in female HL survivors increases linearly with radiation dose. HRT does not appear to increase BC risk for HL survivors with therapy-induced early menopause. There are no indications that endogenous and exogenous gonadal hormones affect the radiation dose-response relationship.
Asunto(s)
Neoplasias de la Mama/etiología , Mama/efectos de la radiación , Hormonas Esteroides Gonadales , Enfermedad de Hodgkin/radioterapia , Neoplasias Inducidas por Radiación/etiología , Adulto , Antineoplásicos/efectos adversos , Antineoplásicos Alquilantes/efectos adversos , Antineoplásicos Alquilantes/uso terapéutico , Mama/efectos de los fármacos , Carcinoma Intraductal no Infiltrante/etiología , Estudios de Casos y Controles , Intervalos de Confianza , Relación Dosis-Respuesta en la Radiación , Femenino , Hormonas Esteroides Gonadales/farmacología , Hormonas Esteroides Gonadales/fisiología , Enfermedad de Hodgkin/tratamiento farmacológico , Terapia de Reemplazo de Hormonas/efectos adversos , Humanos , Menopausia Prematura , Persona de Mediana Edad , Países Bajos , Ovario/fisiología , Procarbazina/efectos adversos , Dosificación Radioterapéutica , Factores de Riesgo , Sobrevivientes , Factores de Tiempo , Adulto JovenRESUMEN
PURPOSE: Cardiovascular diseases are increasingly recognized as late effects of Hodgkin lymphoma (HL) treatment. The purpose of this study was to identify the risk factors for coronary heart disease (CHD) and to quantify the effects of radiation dose to the heart, chemotherapy, and other cardiovascular risk factors. PATIENTS AND METHODS: We conducted a nested case-control study in a cohort of 2,617 5-year HL survivors, treated between 1965 and 1995. Cases were patients diagnosed with CHD as their first cardiovascular event after HL. Detailed treatment information was collected from medical records of 325 cases and 1,204 matched controls. Radiation charts and simulation radiographs were used to estimate in-field heart volume and mean heart dose (MHD). A risk factor questionnaire was sent to patients still alive. RESULTS: The median interval between HL and CHD was 19.0 years. Risk of CHD increased linearly with increasing MHD (excess relative risk [ERR]) per Gray, 7.4%; 95% CI, 3.3% to 14.8%). This results in a 2.5-fold increased risk of CHD for patients receiving a MHD of 20 Gy from mediastinal radiotherapy, compared with patients not treated with mediastinal radiotherapy. ERRs seemed to decrease with each tertile of age at treatment (ERR/Gy(<27.5years), 20.0%; ERR/Gy(27.5-36.4years), 8.8%; ERR/Gy(36.5-50.9years), 4.2%; P(interaction) = .149). Having ≥ 1 classic CHD risk factor (diabetes mellitus, hypertension, or hypercholesterolemia) independently increased CHD risk (rate ratio, 1.5; 95% CI, 1.1 to 2.1). A high level of physical activity was associated with decreased CHD risk (rate ratio, 0.5; 95% CI, 0.3 to 0.8). CONCLUSION: The linear radiation dose-response relationship identified can be used to predict CHD risk for future HL patients and survivors. Appropriate early management of CHD risk factors and stimulation of physical activity may reduce CHD risk in HL survivors.