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BACKGROUND: Sacituzumab govitecan (SG) has been approved by FDA in April 2021 for pre-treated metastatic triple-negative breast cancer (mTNBC), following the ASCENT trial results. METHODS: We set up an ambispective bicentric cohort study to assess the real-world effectiveness and safety of SG in patients with mTNBC treated at Institut Curie Hospitals, with a focus on patients with brain metastases. RESULTS: This study included 99 patients treated through the French Early Access Program to SG from May 2021 to January 2023. Median age was 55 years [26-89], N = 8 patients (8%) had BRCA1/2 mutation, N = 12 (12%) de novo stage IV disease and N = 31 (31%) brain metastases. Patients had previously received a median of two [1-10] lines of treatment in advanced setting. After a median follow-up of 9.7 months, the median progression-free survival (PFS) and overall survival (OS) were 3.9 months (95%CI[3.4-5.0]) and 8.6 months (95%CI[7.1-11.9]), respectively, while objective response rate was 29% (95%CI[21-39]). Among patients with brain metastases, median PFS and OS were 3.7 months (95%CI[2.6-6.2]) and 6.7 months (95%CI[6.3-NR]), respectively, with intracranial tumor responses. Dose reductions were required in N = 17 patients (17%) within a median of three [2-11] cycles, due to gastrointestinal toxicity (N = 6; 6%), hematological toxicity (N = 9; 9%) including febrile neutropenia (N = 2; 2%), liver enzyme elevation (N = 1; 1%), and physical deterioration (N = 1; 1%). There was no related death to SG. CONCLUSIONS: The observed response rate and safety of SG are consistent with the results of the ASCENT trial, with efficacy observed in patients with brain metastases, but observed PFS and OS are numerically shorter.
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Anticorpos Monoclonais Humanizados , Neoplasias Encefálicas , Camptotecina , Neoplasias de Mama Triplo Negativas , Humanos , Pessoa de Meia-Idade , Feminino , Adulto , Idoso , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Idoso de 80 Anos ou mais , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Camptotecina/efeitos adversos , Camptotecina/administração & dosagem , França , Intervalo Livre de Progressão , Estudos Retrospectivos , ImunoconjugadosRESUMO
BACKGROUND: [18F]FDG PET/CT is used for staging and could also provide information associated with clinical outcomes. The objective of this study was to determine the clinical utility of biomarkers measured using [18F]FDG PET/CT to predict the absence of pathological complete response (no-pCR) and recurrence. METHODS: In this retrospective study, we included patients with non-special-type breast carcinoma who underwent [18F]FDG PET/CT before neoadjuvant chemotherapy between 2011 and 2019. Clinicopathological data were collected. Tumor SUVmax and total metabolic tumor volume (TMTV) were measured from PET images. The association between biomarkers and no-pCR was studied using logistic regression. The cut-off value was determined using the area under the ROC Curve. To predict 3-year recurrence-free survival (RFS), we used a multivariable Cox model, and the cut-off value was determined using time-dependent ROC and predictiveness curves. RESULTS: Two hundred and eighty-six patients were included in the analysis. One hundred and twelve patients had a pCR (39.2%). The pCR rate was significantly higher in patients with a high nuclear grade (p < 0.01), HER2+ and TNBC subtypes (p < 0.01), high Ki67 (p < 0.01), and low TMTV (p < 0.01). A high TMTV value (>9.0 cm3) was significantly associated with no-pCR in the whole cohort (OR = 2.4, 95% CI: 1.3-4.2, p < 0.01). After a median follow-up of 4.5 years, 65 patients experienced recurrence and 39 patients died. High TMTV (>13.5 cm3) was associated with shorter RFS (HR = 4.0, 95% CI: 1.9-8.4, p < 0.01). CONCLUSION: High TMTV in pre-therapeutic imaging is associated with no-pCR and recurrence. It can help in identifying high-risk patients and be considered as an intensified or alternative adjuvant therapy for closely monitoring patients.
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Following the results of the IMpassion130 trial, an early access program (EAP) was opened in France, allowing patients with PD-L1-positive advanced triple negative breast cancer (aTNBC) to receive a combination of paclitaxel and atezolizumab as first line therapy. This EAP was later discontinued when the IMpassion131 trial read out with negative results. We performed a retrospective multicentric analysis in patients who were prospectively enrolled in the French EAP. Efficacy and toxicity data were obtained on 64 patients treated from August 2019 to August 2020 in 10 French cancer centers. Median progression-free survival (PFS) and overall survival (OS) were 4.1 months (95% CI [3.0-5.8]) and 17.9 months (95% CI [12.4-NR]), respectively. The 6-months PFS rate was 28% (95% CI [16-40%]) (N = 18/64), while N = 33/64 patients (52%, 95% CI [38-63%]) experienced a tumor response. Exploratory subgroup analyses retrieved that corticosteroid use at inclusion in the EAP, before treatment initiation, was the only independent unfavorable prognostic factor for PFS (HR 2.7, 95% CI [1.3-5.6]). No new safety signal was observed. This real-life study, unique by its setting (EAP granted by anticipation and later withdrawn), suggests atezolizumab and paclitaxel has a limited efficacy in PD-L1-positive aTNBC, especially in patients receiving corticosteroids as comedication before treatment start.
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Paclitaxel , Neoplasias de Mama Triplo Negativas , Humanos , Paclitaxel/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antígeno B7-H1 , Estudos RetrospectivosRESUMO
Supportive care plays a central role in the management of patients with esophagogastric cancers, at all disease stages. Malnutrition has a high prevalence in this population, reaching up to 60 % of the patients. Sarcopenia and cachexia are also common. These complications have negative impact on functional abilities, quality of life and overall survival. They impair anti-tumor treatments effectiveness and increase their toxicity. Early detection and management are needed, before reaching advanced stages, which are refractory to therapeutic interventions. Specific nutritional support is recommended, relying on different nutritional support tools (dietetic counseling, oral supplements, artificial nutrition), depending on the clinical situation. When artificial nutrition is recommended, enteral nutrition (nasogastric tube, gastrostomy or jejunostomy) should be preferred. When enteral nutrition is impossible or insufficient, parenteral nutrition could be necessary. For patients with advanced esophagogastric cancers, digestive prostheses and decompressive radiation therapy may have a symptomatic benefit on dysphagia. Adapted physical activity is also recommended at all stages of cancer care and ongoing clinical trials will help to specify its modalities and to optimize its place in the therapeutic strategy. Finally, psychosocial support could be useful. A combined approach of these different interventions on the nutritional, physical and psychological aspects is beneficial for patients with esophagogastric cancers. This multimodal and multidisciplinary approach applies to both the early stages of the disease, with prehabilitation and/or rehabilitation to reduce perioperative morbidity and mortality and the advanced stages, with a benefit on survival and quality of life, in parallel with anti-tumor treatments.
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Neoplasias Esofágicas , Desnutrição , Neoplasias Gástricas , Humanos , Qualidade de Vida , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/terapia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/terapia , Apoio Nutricional/efeitos adversos , Nutrição Enteral , Desnutrição/etiologia , Desnutrição/prevenção & controleRESUMO
BACKGROUND & AIMS: Predicting the risk of early limiting toxicity (ELT) is major challenge for the clinician seeking an effective, safe treatment for older patients with cancer. The Cancer and Aging Research Group (CARG) and CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) toxicity scores were designed to predict chemotherapy-related toxicity. Elevated resting energy expenditure (REE) may predispose to cachexia and increase ELT and mortality in older patients with cancer. The primary objective was to assess the association between elevated REE and ELT in older patients with cancer. The secondary objectives were to assess the discriminant ability of a predictive model including REE (relative to the CARG and CRASH scores) and the prognostic value of elevated REE. METHODS: We assessed patients aged 70 or over included in the prospective ELCAPA cohort between 2014 and 2018. The inclusion criteria were a solid tumour, a measurement of REE at baseline (mREE, by indirect calorimetry), and a geriatric assessment prior to cancer treatment in a teaching hospital (Paris, France). The mREE was compared with the predicted REE (pREE), as defined by the Harris-Benedict equation. Depending on the mREE/pREE ratio, study participants were classified as hypermetabolic, hypometabolic or normometabolic. The primary endpoint was 3-month ELT, defined as any unplanned hospitalization or any event leading to dose reduction, a treatment delay of more than 7 days, or treatment discontinuation within 3 months of initiation. The secondary endpoint was the 3-month mortality rate. RESULTS: A total of 179 patients were included. The median age was 80 [interquartile range: 76-84] years, 37% of the patients were female, 81.8% had metastatic disease, 67.6% received chemotherapy, 20.7% received hormone therapy, and 11.7% received targeted therapies. According to the mREE/pREE ratio, 85 patients (47%) were hypermetabolic, 63 (35%) were normometabolic, and 31 (18%) were hypometabolic. Sixty patients (33.5%; 95% confidence interval (CI): 26.7-40.9) experienced ELT. The discriminant ability (as assessed by the C-index) of a multivariate model including REE and adjustment factors was 0.82 [95%CI: 0.73-0.91]. In comparison, the discriminant ability of the CARG and CRASH models was 0.57 [0.45-0.68] and 0.51 [0.40-0.62], respectively. In our model, hypermetabolism was an independent risk factor for ELT (adjusted odds ratio = 2.44; 95%CI: 1.02-5.80). Other risk factors were the cancer type and stage, the treatment protocol, a clinical diagnosis of depression, the presence of grade 3 or 4 comorbidities, and the serum lactate dehydrogenase level. CONCLUSION: Hypermetabolism status is an independent predictor of ELT in older patients with cancer, relative to normometabolic status. Baseline REE measurement might improve the ELT risk assessment and decision-making process.
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Metabolismo Basal , Neoplasias , Idoso , Idoso de 80 Anos ou mais , Calorimetria Indireta , Metabolismo Energético , Feminino , Humanos , Masculino , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Estudos ProspectivosRESUMO
High-throughput molecular profiling of solid tumours using core needle biopsies (CNB) allows the identification of actionable molecular alterations, with around 70% success rate. Although several studies have demonstrated the utility of small biopsy specimens for molecular testing, there remains debate as to the sensitivity of the less invasive fine-needle aspiration (FNA) compared to CNB to detect molecular alterations. We aimed to prospectively evaluate the potential of FNA to detect such alterations in various tumour types as compared to CNB in cancer patients included in the SHIVA02 trial. An in-house amplicon-based targeted sequencing panel (Illumina TSCA 99.3 kb panel covering 87 genes) was used to identify pathogenic variants and gene copy number variations (CNV) in concomitant CNB and FNA samples obtained from 61 patients enrolled in the SHIVA02 trial (NCT03084757). The main tumour types analysed were breast (38%), colon (15%), pancreas (11%), followed by cervix and stomach (7% each). We report 123 molecular alterations (85 variants, 23 amplifications and 15 homozygous deletions) among which 98 (80%) were concordant between CNB and FNA. The remaining discordances were mainly related to deletions status, yet undetected alterations were not exclusively specific to FNA. Comparative analysis of molecular alterations in CNB and FNA showed high concordance in terms of variants as well as CNVs identified. We conclude FNA could therefore be used in routine diagnostics workflow and clinical trials for tumour molecular profiling with the advantages of being minimally invasive and preserve tissue material needed for diagnostic, prognostic or theranostic purposes.
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Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias/genética , Neoplasias/patologia , Medicina de Precisão , Biópsia por Agulha Fina , Biópsia com Agulha de Grande Calibre , Variações do Número de Cópias de DNA/genética , DNA de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
Indications of immunotherapy in oncology are continuously expanding, and unconventional types of response have been observed with these new treatments. These include transient progressive disease followed by a partial response, described as pseudoprogression, that raises the question of treatment beyond progression; and rapid disease progression associated with clinical decline, reported as hyperprogression. However, there are currently no consensual definitions of these phenomena and their impact on daily practice remains unclear. We reviewed existing data on pseudoprogression and hyperprogression with a focus on the definitions, incidence, predictive factors, potential biological mechanisms, and methods published to help distinguish pseudoprogression from progression and hyperprogression. The incidence of pseudoprogression ranged from 0 to 15%, with some authors also including disease stabilization after a first progression. For hyperprogression, incidence ranged from 4 to 29% with various definitions, and several authors reported a correlation with worse survival. Both phenomena were observed in a large panel of cancer types. Several radiological and biological methods have been reported to help distinguish pseudoprogression from progression and hyperprogression, such as analysis of radiomics, and circulating-tumor DNA or cell-free DNA, but these need to be confirmed in larger prospective cohorts. In conclusion, pseudoprogression and hyperprogression are both frequent types of responses under immunotherapy, and there is a need to better characterize these to improve the management of cancer patients. Treatment beyond progression should always be considered with caution and necessitates close clinical monitoring. In case of suspected hyperprogression, immunotherapy should be stopped early.
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Imunoterapia , Neoplasias , Progressão da Doença , Humanos , Neoplasias/tratamento farmacológico , Estudos ProspectivosRESUMO
Postsurgical spine imaging actually commences with the preoperative and perioperative imaging examinations that are performed before and during the patient's surgical procedure, respectively. It is in this context that postsurgical spine imaging examinations are best evaluated with a better appreciation of the changes, sometimes dramatic, that can occur following spine surgery. Careful follow-up is the rule in spine surgery, and these patients will have multiple imaging examinations over time. Some studies are performed immediately due to possible complications or exacerbation of pain symptoms, whereas others are used to assess the status of a fusion procedure. In any case it is prudent to always be aware of the overlap between the "normal" or expected imaging findings in the postoperative spine and potential pathologic processes that are developing at the postsurgical site. Additionally, a basic understanding of common spine surgical techniques and approaches is paramount toward rendering a thoughtful analysis. In this chapter, the authors discuss these imaging findings in the setting of the most commonly performed spine surgeries and emphasize the importance of active communication between the radiologist and spine surgeon.
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Diagnóstico por Imagem/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia , HumanosRESUMO
BACKGROUND: Rigid interspinous process fixation (ISPF) has received consideration as an efficient, minimally disruptive technique in supporting lumbar interbody fusion. However, despite advantageous intraoperative utility, limited evidence exists characterizing midterm to long-term clinical outcomes with ISPF. The objective of this multicenter study was to prospectively assess patients receiving single-level anterior (ALIF) or lateral (LLIF) lumbar interbody fusion with adjunctive ISPF. METHODS: This was a prospective, randomized, multicenter (11 investigators), noninferiority trial. All patients received single-level ALIF or LLIF with supplemental ISPF (n = 66) or pedicle screw fixation (PSF; n = 37) for degenerative disc disease and/or spondylolisthesis (grade ≤2). The randomization patient ratio was 2:1, ISPF/PSF. Perioperative and follow-up outcomes were collected (6 weeks, 3 months, 6 months, and 12 months). RESULTS: For ISPF patients, mean posterior intraoperative outcomes were: blood loss, 70.9 mL; operating time, 52.2 minutes; incision length, 5.5 cm; and fluoroscopic imaging time, 10.4 seconds. Statistically significant improvement in patient Oswestry Disability Index scores were achieved by just 6 weeks after operation (P < .01) and improved out to 12 months for the ISPF cohort. Patient-reported 36-Item Short Form Health Survey and Zurich Claudication Questionnaire scores were also significantly improved from baseline to 12 months in the ISPF cohort (P < .01). A total of 92.7% of ISPF patients exhibited interspinous fusion at 12 months. One ISPF patient (1.5%) required a secondary surgical intervention of possible relation to the posterior instrumentation/procedure. CONCLUSION: ISPF can be achieved quickly, with minimal tissue disruption and complication. In supplementing ALIF and LLIF, ISPF supported significant improvement in early postoperative (≤12 months) patient-reported outcomes, while facilitating robust posterior fusion.
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Radiologists are often required to evaluate postoperative spine imaging to assist the surgeon with further clinical management. This article reviews common spine surgical techniques and their proper evaluation on imaging from a surgical perspective. The article attempts to provide a basic surgical foundation for radiologists and a clearer delineation of important points and complications that should be commented on when evaluating the postoperative spine on imaging.