RESUMEN
PURPOSE: The coronavirus disease 2019 (covid-19) caused by the severe acute respiratory syndrome coronavirus 2 (Sars-Cov-2) is at the origin of a global pandemic. This pandemic has prompted the current health system to reorganize and rethink the care offered by health establishments. We report the early and late toxicity in patients infected with covid-19 treated at the same time for early-stage breast cancer. MATERIAL AND METHODS: This is a monocentric prospective study of patients treated in our hospital between March and June 2020 who were diagnosed with covid-19 infection. The inclusion criteria were to be irradiated for early-stage breast cancer and to have a positive covid diagnosis on a polymerase chain reaction (PCR) test and/or a lung computed tomography (CT) scan and/or suggestive clinical symptoms. All of them needed 6 months follow-up clinic after the end of the radiotherapy with clinical examination, mammogram, as well as CT scan to evaluate the lung status. Radiotherapy consisted of breast or chest wall irradiation with or without lymph node irradiation, with protocols adapted to pandemic situation. The treatment-related toxicity was graded according to the Common Toxicology Criteria for Adverse Events (version 4.03). RESULTS: All 350 patients treated for early-stage breast cancer were studied. Of them, 16 presented clinical symptoms of covid-19 infection, and of them 12 had clinical, CT scan and PCR confirmation. This entire cohort of 12 patients with median age of 56years (range: 42-72 years) underwent their radiotherapy. During the radiotherapy, nine patients presented radiodermatitis: eight grade 1 (66%) and one grade 2 (8%). Two patients with lymph nodes irradiation presented grade 2 oesophagitis. Late toxicity was evaluated 6 months after the end of the radiotherapy, and there was no radiation or covid lung sequel on the CT scans. One patient presented covid-related dyspnoea, and two had fibrosis. CONCLUSION: The half-year follow-up of prospective covid-19 cohort, treated for early-stage breast cancer demonstrated an acceptable toxicity profile with few low-grade adverse events. It seems that the covid-19 infection does not appear to increase the side effects of radiotherapy. Therefore radiotherapy should not be delayed.
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Neoplasias de la Mama , COVID-19 , Radiodermatitis , Adulto , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Radiodermatitis/etiología , SARS-CoV-2RESUMEN
PURPOSE: To develop guidelines for and describe the delineation of breast for patients treated in lateral position and to transform this three-dimensional technique based on the virtual simulation to volume-based modern intensity-modulated irradiation technique. MATERIAL AND METHODS: In our department, during the daily delineation, radiation oncologists specialized in breast cancer treatment sought consensus on the delineation of clinical treatment volume of the breast through dialogue based on cases. A radiation oncologist delineated clinical treatment volumes on CT scans of five to 20 patients, followed by a discussion and adaptation of the delineation between all radiation oncologists of the team. The consensus established between clinicians was discussed, corrected and improved. All patients were delineated in treatment position; skin markers were used to visualize the breast tissue after careful palpation. RESULTS: Breast clinical treatment volume was situated and delineated between pectoral muscle and 5mm below the skin (dosimetric considerations), within the space outlined by skin markers, that showed the limits of the palpable breast tissue. In lateral position some vessels were very useful to define the limits as rami mammarii (from thoracica interna) for the internal one and thoracica lateralis for the external. This is the first atlas proposed for the delineation of the breast clinical treatment volumes for breast cancer using alternative technique of breast irradiation (lateral). CONCLUSION: This atlas will be helpful for the volume definition in our daily practice of breast irradiation in lateral position and can open perspectives to develop also atlases for other alternative techniques as treatment in prone position.
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Mama/diagnóstico por imagen , Diagnóstico por Computador/métodos , Posicionamiento del Paciente/métodos , Radioterapia de Intensidad Modulada/métodos , Neoplasias de Mama Unilaterales/diagnóstico por imagen , Neoplasias de Mama Unilaterales/radioterapia , Academias e Institutos , Consenso , Femenino , Humanos , Internado y Residencia , Ilustración Médica , Oncólogos de Radiación , Tomografía Computarizada por Rayos X , Realidad VirtualRESUMEN
Novel patterns of response and progression to immunotherapy have been reported that are not observed with conventional cytotoxic or targeted anticancer treatments. A major breakthrough with immunotherapy is its potential to achieve durable responses in a subset of patients with advanced cancer that can be maintained several years even after stopping the treatment. No standardized definition of durable response exists in the literature, and the optimal duration of treatment in case of durable response is not clearly established. However, the majority of patients do not respond to immunotherapy. Initially reported in advanced melanoma patients, pseudoprogression occurs when tumor index lesions regress after initial progression, supporting the concept of treating some patients beyond progression. Overall, reported rates of pseudoprogression never exceeded 10%, meaning that the large majority of patients who have a disease progression will not eventually respond to treatment. The decision to pursue treatment beyond progression must therefore only be taken in carefully selected patients with clinical benefit, who did not experience severe toxicities with immunotherapy. Conversely, rapid progressions, called hyperprogressions, were reported by several teams with rates ranging from 4% to 29%. These observations need to be confirmed from randomized trials. It is essential to interrupt the treatment in patients with hyperprogression, in order to switch to another potentially active treatment. Finally, some patients experience dissociated responses, with some lesions shrinking and others growing. Local treatment with surgery or radiotherapy for growing lesions may be considered. Several immune-specific-related response criteria were developed to better capture benefits of immunotherapy. These criteria only address the pseudoprogression pattern of response, and do not capture the other patterns of response such as hyperprogression and dissociated response. The classic RECIST remains a reasonable and meaningful method to assess response to immunotherapy in the clinic.
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Inmunoterapia , Neoplasias/epidemiología , Neoplasias/terapia , Criterios de Evaluación de Respuesta en Tumores Sólidos , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Neoplasias/patología , Supervivencia sin Progresión , Resultado del TratamientoRESUMEN
BACKGROUND: Recent clinical results support the use of new immune checkpoint blockers (ICB), such as anti-PD-1 (e.g. nivolumab and pembrolizumab) and anti-PD-L1 antibodies. Radiological evaluation of ICB efficacy during therapy is challenging due to tumor immune infiltration. Changes of circulating tumor DNA (ctDNA) levels during therapy could be a promising tool for very accurate monitoring of treatment efficacy, but data are lacking with ICB. PATIENTS AND METHODS: This prospective pilot study was conducted in patients with nonsmall cell lung cancer, uveal melanoma, or microsatellite-instable colorectal cancer treated by nivolumab or pembrolizumab monotherapy at Institut Curie. ctDNA levels were assessed at baseline and after 8 weeks (w8) by bidirectional pyrophosphorolysis-activated polymerization, droplet digital PCR or next-generation sequencing depending on the mutation type. Radiological evaluation of efficacy of treatment was carried out by using immune-related response criteria. RESULTS: ctDNA was detected at baseline in 10 out of 15 patients. At w8, a significant correlation (r = 0.86; P = 0.002) was observed between synchronous changes in ctDNA levels and tumor size. Patients in whom ctDNA levels became undetectable at w8 presented a marked and lasting response to therapy. ctDNA detection at w8 was also a significant prognostic factor in terms of progression-free survival (hazard ratio = 10.2; 95% confidence interval 2.5-41, P < 0.001) and overall survival (hazard ratio = 15; 95% confidence interval 2.5-94.9, P = 0.004). CONCLUSION: This proof-of-principle study is the first to demonstrate that quantitative ctDNA monitoring is a valuable tool to assess tumor response in patients treated with anti-PD-1 drugs.
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Antígeno B7-H1/antagonistas & inhibidores , ADN de Neoplasias/sangre , Inmunoterapia , Monitoreo Fisiológico , Neoplasias/terapia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/patología , Proyectos Piloto , Reacción en Cadena de la Polimerasa , Pronóstico , Estudios Prospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND: Pembrolizumab and nivolumab are immune checkpoint inhibitors targeting PD-1 that have recently been approved in pretreated recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. In the clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents but rather to experience an acceleration of tumor growth kinetics (TGK). PATIENTS AND METHODS: We retrospectively compared TGK on immunotherapy and TGK on last treatment in patients with R/M HNSCC treated with PD-1/PD-L1 inhibitors in four French centers. The TGK ratio (TGKR, ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. Hyperprogression was defined as a TGKR ≥ 2. RESULTS: From September 2012 to September 2015, 34 patients were identified. Patterns of recurrence included exclusive loco-regional recurrence in 14 patients, exclusive distant metastases in 11 patients, and both in 9 patients. No pseudo-progression was observed. Hyperprogression was observed in 10 patients (29%), including 9 patients with at least a locoregional recurrence, and only 1 patient with exclusively distant metastases. Hyperprogression significantly correlated with a regional recurrence (TGKR ≥ 2: 90% versus TGKR < 2: 37%, P = 0.008), but not with local or distant recurrence. Hyperprogression was associated with a shorter progression-free survival (PFS) according to RECIST (P = 0.003) and irRECIST (P = 0.02), but not with overall survival (P = 0.77). CONCLUSIONS: Hyperprogression was observed in 29% of patients with R/M HNSCC treated with anti-PD-L1/PD-1 agents and correlated with a shorter PFS. It occurred in 39% of patients with at least a locoregional recurrence and 9% of patients with exclusively distant metastases. No pseudo-progressions were reported. Mechanisms and causality of hyperprogression should further be assessed through prospective controlled studies.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Antígeno B7-H1/antagonistas & inhibidores , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Recurrencia Local de Neoplasia , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Nivolumab , Receptor de Muerte Celular Programada 1/inmunología , Estudios Retrospectivos , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y Cuello , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacosRESUMEN
Background: Several studies used the ratio of progression-free survival (PFS) on genotype-matched treatment to PFS on genotype-unmatched treatment to assess the efficacy of therapy guided by patients' tumor molecular profiling. We evaluated the PFS ratio from patients who cross-over in the SHIVA trial. Patients and methods: The primary end point of the SHIVA trial was to compare PFS on molecularly targeted agents (MTAs) based on tumor molecular profiling and treatment at physician's choice (TPC) in patients with any kind of cancer who had failed standard-of-care therapy. The experimental treatment included only marketed MTAs given outside their indications according to a pre-specified treatment algorithm. Patients were allowed to cross-over at disease progression in both arms. Response was evaluated according to RECIST 1.1 at randomization and at cross-over. We evaluated the ratio of PFS on MTA (PFSMTA) to PFS on TPC (PFSTPC) in patients who crossed-over. Results: Among 741 patients enrolled in the SHIVA trial, 197 were randomized, and 95 crossed-over, including 70 patients from the TPC to the MTA arm and 25 patients from the MTA to the TPC arm. Two patients crossed-over in the TPC arm without disease progression. The PFSMTA/PFSTPC ratio exceeded 1.3 in 37% of patients who crossed-over from the TPC to the MTA arm. The PFSMTA/PFSTPC ratio exceeded 1.3 in 61% of patients who crossed-over from the MTA arm to the TPC arm. Conclusions: The cross-over analysis of the SHIVA trial identified 37% of patients who crossed-over from TPC to MTA with a PFSMTA/PFSTPC ratio exceeding 1.3.
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Supervivencia sin Enfermedad , Terapia Molecular Dirigida , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios Cruzados , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/patología , Selección de Paciente , Medicina de Precisión , Nivel de AtenciónRESUMEN
BACKGROUND: The aim of the study was to analyse efficacy, safety, and health-related quality of life (HRQoL) for sorafenib treatment in patients with metastatic uveal melanoma. METHODS: A multicentre, single-arm phase II trial was conducted. The primary objective was to determine the non-progression rate (RECIST) at 24 weeks for patients receiving sorafenib at a dose of 800 mg per day. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and HRQoL. RESULTS: Thirty-two patients were included. Ten patients showed non-progression at 24 weeks (31.2%) without objective tumour responses. The estimated 24-week PFS was 31.2% (95% CI: 14.8%-47.6%) and the estimated 24-week OS was 62.5% (95% CI: 45.4%-79.6%). Ten patients (34.3%) had at least one grade 3 or 4 adverse reaction and 12 patients (41.4%) required dose modifications due to toxicity. At 24 weeks, no patient had an improvement in global HRQoL and 87.5% experienced a permanent increase in physical fatigue. CONCLUSIONS: Sorafenib demonstrated non-progression at 24 weeks in 31.2% of patients. However, 41.4% of patients required dose modifications due to toxicity and no improvement in HRQoL was demonstrated.
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Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Melanoma/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/uso terapéutico , Neoplasias de la Úvea/tratamiento farmacológico , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Calidad de Vida , SorafenibRESUMEN
BACKGROUND: The resection of liver metastasis from uveal melanoma (LMUM) remains controversial. In this study, we evaluated treatment with radiofrequency ablation (RFA) for liver metastases alone or in combination with surgical liver resection. METHODS: A total of 72 patients with LMUM were evaluated in this study. Of these, 57 patients underwent surgical resection (S) while 15 patients had RFA ± S. Clinicopathologic factors were evaluated in terms of recurrence and survival using Chi-square and log-rank tests, respectively. RESULTS: We studied 22 metastases treated by RFA. There were no statistically significant differences between the groups in terms of median age of onset, synchronous nature of the metastases, time from primary tumour treatment to liver metastasis, diameter of the largest metastasis, presence of liver miliary disease, and the type of liver resection. There was a statistically lower number of liver metastases and more bilobar metastases in the RFA group than in the S group. The median overall survival after liver surgery was 27 months in group S and 28 months in the RFA group ± S. The median disease-free survival was 10 months in group S and 7 months in the RFA group ± S. There were no statistically significant differences in the median overall survival and disease-free survival between groups. CONCLUSIONS: The results of this retrospective analysis show that RFA can be used to treat liver metastases to spare the hepatic parenchyma. RFA ± liver surgery and liver surgery alone demonstrate similar survival times.
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Ablación por Catéter/métodos , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Melanoma/cirugía , Neoplasias de la Úvea/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Hepáticas/secundario , Imagen por Resonancia Magnética , Masculino , Melanoma/secundario , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Despite advances in the local treatment of UM, half of patients develop metastases typically to the liver with poor survival. Microscopic complete surgical resection (R0) of liver metastases improves survival in high selected patients. Early identification of high-risk patients might allow detection of asymptomatic metastases, and increase R0 liver surgery rate. From October 2006 to December 2009, we conducted a prospective study to detect early minimal lesions with 6-monthly liver function tests (LFTs) and liver MRI in 100 high-risk patients. High risk was defined by primary tumor clinical or genomic criteria: thickness>8mm or diameter>15 mm, or extra-scleral extension, or monosomy 3 by FISH or aCGH. With a median follow-up of 49 months, the 5-year metastasis-free survival and overall survival were 47 and 33%, respectively. Of the 60 patients who became metastatic, 50 (83%) had exclusive liver metastasis. LFTs screening had no sufficient accurary, but biannual MRI showed high predictive value to detect metastasis and select patients eligible for curative surgery: 25/50 underwent laparotomy and among them, 8/25 (32%) had a R0 surgery. Median survival after metastasis was 14 months, mean survival reached 40 months in the R0 resected population. Six-monthly liver MRI screening is recommended in patients with large tumors or genomic high risk in order to detect early patient candidates to complete resection of liver metastases.
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Diagnóstico Precoz , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Melanoma/diagnóstico , Melanoma/secundario , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/secundario , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Supervivencia sin Enfermedad , Intervención Médica Temprana , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Pruebas de Función Hepática , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética , Masculino , Melanoma/genética , Melanoma/mortalidad , Melanoma/cirugía , Metastasectomía/métodos , Microcirugia/métodos , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/mortalidad , Neoplasias de la Úvea/cirugía , Adulto JovenRESUMEN
BACKGROUND: HER3 activating mutations have been shown in preclinical models to be oncogenic and ligand-independent, but to depend on kinase-active HER2. PATIENTS AND METHODS: Whole-exome sequencing of the primary HER2-negative breast cancer and its HER2-negative synchronous liver metastasis from a 46-year-old female revealed the presence of an activating and clonal HER3 G284R mutation. RESULTS: HER2 dual blockade with trastuzumab and lapatinib as third-line therapy led to complete metabolic response in 2 weeks and confirmed radiological partial response after 8 weeks. Following the resection of the liver metastasis, the patient remains disease-free 40 weeks after initiation of the HER2 dual blockade therapy. Immunohistochemical analysis demonstrated a substantial reduction of phospho-rpS6 and phospho-AKT in the post-therapy biopsy of the liver metastasis. DISCUSSION: This is the first-in-man evidence that anti-HER2 therapies are likely effective in breast cancers harboring HER3 activating mutations.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-3/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Femenino , Humanos , Lapatinib , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Mutación , Quinazolinas/administración & dosificación , Receptor ErbB-2/metabolismo , Trastuzumab/administración & dosificaciónRESUMEN
The clinical validity of circulating tumor cell (CTC) count changes during chemotherapy in metastatic breast cancer patients has been validated, but its clinical utility remains to be demonstrated. We report here the non-randomized run-in phase of the CirCe01 trial which was designed to evaluate CTC changes and thresholds to other palliative prognostic scores and establish CTC thresholds to be used in the randomized part of the study. CTC count (CellSearch®) and other prognostic parameters (serum albumin level, lymphocyte level, LDH level, prognostic inflammatory and nutritional index (PINI) and Barbot's score) were assessed in 56 metastatic breast cancer patients before the first cycle of third line chemotherapy. Early changes of CTC count were correlated with treatment outcome. Independent prognostic markers in multivariate analysis were: low serum albumin (HR = 11.1), poor performance status (HR = 3.8), ≥5 CTC/7.5 ml (HR = 3.8) and triple negative subtype (HER2+ and hormone positive vs triple negative: both HR = 0.2). Among patients with ≥5 CTC/7.5 ml at baseline, a composite criteria (<5 CTC/7.5 ml or relative decrease ≥-70% of the baseline CTC count) showed better prognostication for PFS (p=0.002).
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Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Células Neoplásicas Circulantes/patología , Neoplasias de la Mama/tratamiento farmacológico , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Tasa de SupervivenciaRESUMEN
The cervico-thoracic-abdominal-pelvic CT-scan is a key examination of the staging of esophagus cancers. Anatomical and pathophysiological knowledge of the lymph nodes is an essential tool to establish a precise mapping. Imaging tests (such endoscopic ultrasound and PET scanning) will be very useful to determine clinical options and clinical target volume delineation for the radiotherapy of esophagus cancers.
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Adenocarcinoma/secundario , Carcinoma de Células Escamosas/secundario , Neoplasias Esofágicas/patología , Metástasis Linfática/diagnóstico , Adenocarcinoma/diagnóstico por imagen , Carcinoma de Células Escamosas/diagnóstico por imagen , Medios de Contraste , Endosonografía , Humanos , Metástasis Linfática/diagnóstico por imagen , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The SHIVA trial is a multicentric randomised proof-of-concept phase II trial comparing molecularly targeted therapy based on tumour molecular profiling vs conventional therapy in patients with any type of refractory cancer. RESULTS of the feasibility study on the first 100 enrolled patients are presented. METHODS: Adult patients with any type of metastatic cancer who failed standard therapy were eligible for the study. The molecular profile was performed on a mandatory biopsy, and included mutations and gene copy number alteration analyses using high-throughput technologies, as well as the determination of oestrogen, progesterone, and androgen receptors by immunohistochemistry (IHC). RESULTS: Biopsy was safely performed in 95 of the first 100 included patients. Median time between the biopsy and the therapeutic decision taken during a weekly molecular biology board was 26 days. Mutations, gene copy number alterations, and IHC analyses were successful in 63 (66%), 65 (68%), and 87 (92%) patients, respectively. A druggable molecular abnormality was present in 38 patients (40%). CONCLUSIONS: The establishment of a comprehensive tumour molecular profile was safe, feasible, and compatible with clinical practice in refractory cancer patients.
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Neoplasias/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Análisis Mutacional de ADN , Femenino , Dosificación de Gen , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida/métodos , Neoplasias/genética , Neoplasias/metabolismo , Medicina de Precisión/métodosRESUMEN
PURPOSE: To describe the procedure of definition of the boost volume using pre- and post-operative computed tomography (CT) and surgical clips in the tumor bed after oncoplastic surgical procedure. PATIENTS AND METHODS: Thirty-one consecutive breast cancer patients who underwent simple lumpectomy or oncoplastic surgery were studied. All of them underwent pre- and post-operative CT scan in treatment position to evaluate the planning target volume (PTV) boost volume and define the primary tumor (gross tumor volume (GTV)) and tumor bed zones (CTV), with an overall margin of 5 mm in lateral and 10 mm in craniocaudal directions, corresponding to localization and setup uncertainties. RESULTS: Thirteem patients underwent simple lumpectomy and 18 oncoplastic surgery. The volumetric analysis showed that the intersection between GTV and CTV clips was significantly higher in patients with three and more clips (28.4% vs 3.14%; p < 0.001). In the case of patients with oncoplastic surgery, more than three clips were needed to define the tumor bed volume with accuracy. The number of clips was directly related to the exact definition of the boost volume. CONCLUSIONS: The use of more than three clips allows better definition of the PTV boost volume after oncoplastic surgical procedure.
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Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Mamoplastia/métodos , Mastectomía Segmentaria/métodos , Adulto , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Proyectos Piloto , Cuidados Posoperatorios , Cuidados Preoperatorios/métodos , Dosificación Radioterapéutica , Radioterapia Adyuvante , Estudios Retrospectivos , Medición de Riesgo , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Carga Tumoral/efectos de la radiaciónRESUMEN
AIM: To determine whether, in a highly selected patient population, medical treatment combined with surgical resection of liver metastases from breast cancer is associated with improved survival compared with medical treatment alone. PATIENTS AND METHODS: Between 1988 and 2007, 100 liver resections for metastatic breast cancer were performed at Institut Curie, 51 of which met the criteria for inclusion in this case-control study. With the exception of bone metastases, patients with other distant metastasis sites were excluded. Surgery was only performed in patients with stable disease or disease responding to medical treatment evaluated by imaging evaluation. Surgical cases were individually matched with 51 patients receiving medical treatment only. All patients had 4 or fewer resectable liver metastases. The study group was matched with the control group for age, year of breast cancer diagnosis, time to metastasis, TNM stage, hormone receptor status and breast cancer tumour pathology. RESULTS: Univariate analysis confirmed a survival advantage for patients lacking bone metastases and axillary lymphadenopathy at the time of breast cancer diagnosis and for surgically treated patients. Multivariate analysis indicated that surgery and the absence of bone metastases were associated with a better prognosis. A multivariate Cox model adapted for paired data showed a RR = 3.04 (CI: 1.87-4.92) (p < 0.0001) in favour of surgical treatment. CONCLUSION: Surgical resection of liver metastases from primary breast cancer appears to provide a survival benefit for highly selected patients.
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Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Estudios de Casos y Controles , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/tratamiento farmacológico , Metástasis Linfática , Persona de Mediana Edad , Modelos de Riesgos ProporcionalesRESUMEN
OBJECTIVE: To assess the visualisation of the left anterior descending (LAD) coronary artery on CT images used for breast radiation treatment planning. METHODS: Delineation of the LAD artery was achieved for 25 breast patients by 1 radiologist and 1 radiation oncologist independently on two sets of images for each patient: one pre-operative CT scan using intravenous (IV) contrast media to determine the primary gross tumour volume (GTV) and one post-operative CT scan used for treatment planning. A Student's paired t-test was used to compare the number of CT slices in which the LAD was visible for each patient in the two series. Interpolations and extrapolations of the LAD volume were performed for the left-sided cases using a published heart atlas in order to report doses to the LAD structure. RESULTS: There was a non-significant difference between the results with and without IV contrast media (p=0.34 for the radiologist; p=0.90 for the radiation oncologist). The visible LAD artery corresponded to a 30% portion (range 12-47%) of the interpolated structure. The maximum dose to the left artery varied widely, from 2.7 to 41.7 Gy, in the group of patients with left breast tumours. The largest values (>25 Gy) corresponded to those patients in whom the LAD artery distal extremity lay inside the breast fields. CONCLUSIONS: With the current planning CT protocol, only one-third of the LAD artery could be objectively visualised. Contrast-enhanced imaging used for GTV delineation before the breast surgery did not improve the visualisation of the artery. ADVANCES IN KNOWLEDGE: This study has revealed the lack of consistency that may be encountered when contouring heart vessels, thereby questioning the reliability of dose reporting.
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Neoplasias de la Mama/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Planificación de la Radioterapia Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Neoplasias de la Mama/patología , Medios de Contraste , Femenino , Humanos , Persona de Mediana Edad , Variaciones Dependientes del Observador , Intensificación de Imagen Radiográfica/métodos , Reproducibilidad de los Resultados , Carga TumoralRESUMEN
The majority of patients who develop liver metastases in metastatic colorectal cancer (mCRC) has often unresectable disease. Several new methods of nonsurgical ablation have been tested with variable success. Helical tomotherapy (HT), such as intensity-modulated radiation therapy (IMRT) or stereotactic body radiotherapy therapy, is a recent radiation therapy technique which can provide simultaneous and precise targeting of multiple lesions, while sparing normal tissues. We retrospectively assess the feasibility and the tolerance of IMRT with capecitabine followed by hepatic surgery in mCRC patients. This original observation suggests that HT could be safely integrated in the multidisciplinary management of patients with metastatic colorectal cancer as an alternative to surgery or other local ablation therapies.
Asunto(s)
Carcinoma/terapia , Neoplasias Colorrectales/terapia , Neoplasias Hepáticas/terapia , Radioterapia de Intensidad Modulada/métodos , Antineoplásicos/administración & dosificación , Capecitabina , Carcinoma/secundario , Neoplasias Colorrectales/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Hepatectomía , Humanos , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Recurrencia Local de Neoplasia/terapiaRESUMEN
BACKGROUND: Treatment effect is categorised into four classes by RECIST based on the evolution of the size of target lesions and the occurrence of new lesions, irrespective of tumour growth kinetics before treatment. This study aimed at evaluating the added value of tumour growth kinetics assessment to RECIST in patients treated with molecularly targeted agents (MTAs). METHODS: On-study imaging, along with pre-baseline imaging, of patients treated with MTA(s) in clinical trials at Institut Curie were centrally reviewed. The tumour growth ratio (TGr), defined as the ratio of the slope of tumour growth before treatment and the slope of tumour growth on treatment between the nadir and disease progression, was calculated for each patient. RESULTS: A total of 50 patients included in 18 trials were eligible for the study. Among the 44 patients who withdrew from the study because of disease progression according to the investigators' assessment, 18 patients (41%) had a TGr <0.9. Among these 18 patients, 5 had disease progression according to RECIST 1.1 based on our retrospective reassessment of on-study imaging and occurrence of no new lesion during study treatment. CONCLUSION: Our preliminary results suggest that a substantial proportion of patients treated with MTAs have discontinued treatment although being potentially benefitted from them.
Asunto(s)
Antineoplásicos/uso terapéutico , Terapia Molecular Dirigida , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Adolescente , Adulto , Anciano , Proliferación Celular , Diagnóstico por Imagen , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: The definition of the optimal dose of a new compound and the design for identifying this dose have been set up for treatment with cytotoxic activity. The optimal dose is typically the Maximum Tolerated Dose (MTD) defined by the occurrence of severe toxic side effects during the first course of treatment. In the era of molecularly targeted therapies (MTA), where the mechanistic relations between the dose, the activity and the toxicity are probably different, how relevant these definitions and designs are? METHODS: We present here a review of the outcomes of potential interest for defining the optimal dose and we present several statistical innovative dose finding methods. Longitudinal data (tumour growth, repeated evaluation of toxic side effects) and continuous outcomes appear particularly promising for early phase trials. CONCLUSIONS: Phase I dose finding method for molecularly targeted agents should continue to identify the MTD, but the dose recommended for phase II trials should not be systematically defined as the MTD and should incorporate other endpoints. In particular, more sensitive and more discriminatory endpoints are necessary. They needn't be good surrogate of the clinical benefit, but they should allow for ranking several doses. Experience from other medical specialties, such as phase II dose-ranging trials could be considered.
Asunto(s)
Antineoplásicos/administración & dosificación , Dosis Máxima Tolerada , Terapia Molecular Dirigida/métodos , Neoplasias/tratamiento farmacológico , Antineoplásicos/efectos adversos , Antineoplásicos/sangre , Biomarcadores de Tumor/sangre , Supervivencia Celular , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Clorhidrato de Erlotinib , Gefitinib , Humanos , Neoplasias/sangre , Neoplasias/patología , Neovascularización Patológica/diagnóstico , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The aim of this study was to present the simplified rules of delineation of lymph node (LN) volumes in breast irradiation. Practical rules of delineation of LN areas were developed in the Department of Radiation Oncology of the Institut Curie. These practical guidelines of delineation were based on different specific publications in the field of breast and LN anatomy. The principal characteristic of these rules is their clearly established relationship with anatomical structure, which is easy to find on CT slices. The simplified rules of delineation have been published in pocket format as the illustrated atlas "Help of delineation for breast cancer treatment". In this small pocket guide, delineation using the practical rules is illustrated, with examples from anatomical CT slices. It is shown that there is an improvement in delineation after the use of these simplified rules and the guide. In conclusion, this small guide is useful for improving everyday practice and decreasing the differences in target delineation for breast irradiation between institutions and observers.