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INTRODUCTION: Breast cancer is the most common malignancy among women in the world. The role of neoadjuvant chemotherapy (NAC) in the management of breast cancer is increasing. The decision about the management after NAC depends mainly on the tumor response to NAC. OBJECTIVES: The role of the current study is to evaluate the role of the MRI scan in assessing the residual disease after NAC, which would help in decision making regarding the best treatment plan for the patient. PATIENTS AND METHODS: We did this retrospective review for all patients who were diagnosed with breast cancer in our center and had NAC over four years. All patients in our study had a post-NAC magnetic resonance imaging (MRI) scan to assess the residual tumor size. A 2×2 table was used to calculate the diagnostic accuracy, and SPSS software version 25 was used to get the correlation coefficients between the post-NAC MRI measurements and pathological size. RESULTS: 28 female patients were included in our study. The average age was 45.25 ± 10 years. We utilized the tumor size on histology as the standard for comparison. We calculated MRI sensitivity, specificity, PPV, and NPV rates of 90.9%, 100%, 100%, and 94.4%, respectively. The correlation coefficient was strong (r = 0.859, P = 0.01). CONCLUSION: Magnetic resonance imaging is a good test to assess the residual tumor disease after NAC in breast cancer patients. However, cases of under- and overestimation are still seen, which require more caution when making a decision regarding the management of such cases.
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Neoplasias da Mama, Feminino, Humanos, Adulto, Pessoa de Meia-Idade, Neoplasias da Mama/diagnóstico por imagem, Neoplasias da Mama/tratamento farmacológico, Neoplasias da Mama/patologia, Terapia Neoadjuvante/métodos, Neoplasia Residual/diagnóstico por imagem, Neoplasia Residual/patologia, Mama/patologia, Imageamento por Ressonância Magnética/métodos, Estudos Retrospectivos, Quimioterapia AdjuvanteRESUMO
BACKGROUND: Breast cancer patients with residual disease after neoadjuvant systemic treatment (NAST) have a worse prognosis compared with those achieving a pathologic complete response (pCR). Earlier identification of these patients might allow timely, extended neoadjuvant treatment strategies. We explored the feasibility of a vacuum-assisted biopsy (VAB) after NAST to identify patients with residual disease (ypT+ or ypN+) prior to surgery. METHODS: We used data from a multicenter trial, collected at 21 study sites (NCT02948764). The trial included women with cT1-3, cN0/+ breast cancer undergoing routine post-neoadjuvant imaging (ultrasound, MRI, mammography) and VAB prior to surgery. We compared the findings of VAB and routine imaging with the histopathologic evaluation of the surgical specimen. RESULTS: Of 398 patients, 34 patients with missing ypN status and 127 patients with luminal tumors were excluded. Among the remaining 237 patients, tumor cells in the VAB indicated a surgical non-pCR in all patients (73/73, positive predictive value [PPV] 100%), whereas PPV of routine imaging after NAST was 56.0% (75/134). Sensitivity of the VAB was 72.3% (73/101), and 74.3% for sensitivity of imaging (75/101). CONCLUSION: Residual cancer found in a VAB specimen after NAST always corresponds to non-pCR. Residual cancer assumed on routine imaging after NAST corresponds to actual residual cancer in about half of patients. Response assessment by VAB is not safe for the exclusion of residual cancer. Response assessment by biopsies after NAST may allow studying the new concept of extended neoadjuvant treatment for patients with residual disease in future trials.
Assuntos
Neoplasias da Mama, Humanos, Feminino, Neoplasias da Mama/tratamento farmacológico, Neoplasias da Mama/cirurgia, Neoplasias da Mama/patologia, Terapia Neoadjuvante/métodos, Neoplasia Residual/patologia, Mama/patologia, Biópsia Guiada por Imagem/métodosRESUMO
PURPOSE: To develop and validate a radiomics model based on high-resolution T2WI and a clinical-radiomics model for tumour-stroma ratio (TSR) evaluation with a gold standard of TSR evaluated by rectal specimens without therapeutic interference and further apply them in prognosis prediction of locally advanced rectal cancer (LARC) patients who received neoadjuvant chemoradiotherapy. METHODS: A total of 178 patients (mean age: 59.35, range 20-85 years; 65 women and 113 men) with rectal cancer who received surgery alone from January 2016 to October 2020 were enrolled and randomly separated at a ratio of 7:3 into training and validation sets. A senior radiologist reviewed after 2 readers manually delineated the whole tumour in consensus on preoperative high-resolution T2WI in the training set. A total of 1046 features were then extracted, and recursive feature elimination embedded with leave-one-out cross validation was applied to select features, with which an MR-TSR evaluation model was built containing 6 filtered features via a support vector machine classifier trained by comparing patients' pathological TSR. Stepwise logistic regression was employed to integrate clinical factors with the radiomics model (Fusion-TSR) in the training set. Later, the MR-TSR and Fusion-TSR models were replicated in the validation set for diagnostic effectiveness evaluation. Subsequently, 243 patients (mean age: 53.74, range 23-74 years; 63 women and 180 men) with LARC from October 2012 to September 2017 who were treated with NCRT prior to surgery and underwent standard pretreatment rectal MR examination were enrolled. The MR-TSR and Fusion-TSR were applied, and the Kaplan-Meier method and log-rank test were used to compare the survival of patients with different MR-TSR and Fusion-TSR. Cox proportional hazards regression was used to calculate the hazard ratio (HR). RESULTS: Both the MR-TSR and Fusion-TSR models were validated with favourable diagnostic power: the AUC of the MR-TSR was 0.77 (p = 0.01; accuracy = 69.8 %, sensitivity = 88.9 %, specificity = 65.9 %, PPV = 34.8 %, NPV = 96.7 %), while the AUC of the Fusion-TSR was 0.76 (p = 0.014; accuracy = 67.9 %, sensitivity = 88.9 %, specificity = 63.6 %, PPV = 33.3 %, NPV = 96.6 %), outperforming their effectiveness in the training set: the AUC of the MR-TSR was 0.65 (p = 0.035; accuracy = 66.4 %, sensitivity = 61.9 %, specificity = 67.3 %, PPV = 27.7 %, NPV = 90.0 %), while the AUC of the Fusion-TSR was 0.73 (p = 0.001; accuracy = 73.6 %, sensitivity = 71.4 %, specificity = 74.0 %, PPV = 35.73 %, NPV = 92.8 %). With further prognostic analysis, the MR-TSR was validated as a significant prognostic factor for DFS in LARC patients treated with NCRT (p = 0.020, HR = 1.662, 95 % CI = 1.077-2.565), while the Fusion-TSR was a significant prognostic factor for OS (p = 0.005, HR = 2.373, 95 % CI = 1.281-4.396). CONCLUSIONS: We developed and validated a radiomics TSR and a clinical-radiomics TSR model and successfully applied them to better risk stratification for LARC patients receiving NCRT and for better decision making.
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Segunda Neoplasia Primária, Neoplasias Retais, Masculino, Humanos, Feminino, Adulto Jovem, Adulto, Pessoa de Meia-Idade, Idoso, Idoso de 80 Anos ou mais, Prognóstico, Radiômica, Imageamento por Ressonância Magnética/métodos, Reto/patologia, Neoplasias Retais/diagnóstico por imagem, Neoplasias Retais/terapia, Neoplasias Retais/patologia, Segunda Neoplasia Primária/patologia, Terapia Neoadjuvante/métodos, Estudos RetrospectivosRESUMO
BACKGROUND: Platinum-based neoadjuvant chemotherapy (NAC) is standard for patients with muscle-invasive bladder cancer (MIBC). Pathologic response (complete: ypT0N0 and partial: Assuntos
Cisplatino, Neoplasias da Bexiga Urinária, Humanos, Terapia Neoadjuvante/métodos, Gencitabina, Nivolumabe/uso terapêutico, Proteômica, Microambiente Tumoral, Neoplasias da Bexiga Urinária/tratamento farmacológico, Neoplasias da Bexiga Urinária/patologia, Biomarcadores Tumorais, Músculos/patologia, Imunoterapia, Invasividade Neoplásica, Cistectomia
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PURPOSE: Evidence supports the value of shorter, similarly efficacious, and potentially more cost-effective hypofractionated radiation therapy (RT) regimens in many clinical scenarios for breast cancer (BC) and prostate cancer (PC). However, practice patterns vary considerably. We used the most recent Centers for Medicare and Medicaid Services data to assess trends in RT cost and practice patterns among episodes of BC and PC. METHODS AND MATERIALS: We performed a retrospective cohort analysis of all external beam RT episodes for BC and PC from 2015 to 2019 to assess predictors of short-course RT (SCRT) use and calculated spending differences. Multivariable logistic regression defined adjusted odds ratios of receipt of SCRT over longer-course RT (LCRT) by treatment modality, age, year of diagnosis, type of practice, and the interaction between year and treatment setting. Medicare spending was evaluated using multivariable linear regression controlling for duration of RT regimen (SCRT vs LCRT) in addition to the above covariables. RESULTS: Of 143,729 BC episodes and 114,214 PC episodes, 63,623 (44.27%) and 25,955 (22.72%) were SCRT regimens, respectively. Median total spending for SCRT regimens among BC episodes was $9418 (interquartile range [IQR], $7966-$10,983) versus $13,602 (IQR, $11,814-$15,499) for LCRT. Among PC episodes, median total spending was $6924 (IQR, $4,509-$12,905) for stereotactic body RT, $18,768 (IQR, $15,421-$20,740) for moderate hypofractionation, and $27,319 (IQR, $25,446-$29,421) for LCRT. On logistic regression, receipt of SCRT was associated with older age among both BC and PC episodes as well as treatment at hospital-affiliated over freestanding sites (P < .001 for all). CONCLUSIONS: In this evaluation of BC and PC RT episodes from 2015 to 2019, we found that shorter-course RT resulted in lower costs than longer-course RT. SCRT was also more common in hospital-affiliated sites. Future research focusing on potential payment incentives encouraging SCRT when clinically appropriate in the 2 most common cancers treated with RT will be valuable as the field continues to prospectively evaluate cost-effective hypofractionation in other disease sites.
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Neoplasias da Mama, Neoplasias da Próstata, Masculino, Humanos, Idoso, Estados Unidos, Medicare, Estudos Retrospectivos, Terapia Neoadjuvante/métodosRESUMO
BACKGROUND: The outcome of patients with resectable mucosal melanoma is poor. Toripalimab combined with axitinib has shown impressive results in metastatic mucosal melanoma with an objective response rate of 48.3% and a median progression-free survival of 7.5 months in a phase Ib trial. It was hypothesized that this combination administered in the neoadjuvant setting might induce a pathologic response in resectable mucosal melanoma, so we conducted this trial. PATIENTS AND METHODS: This single-arm phase II trial enrolled patients with resectable mucosal melanoma. Patients received toripalimab 3 mg/kg once every 2 weeks (Q2W) plus axitinib 5 mg two times a day (b.i.d.) for 8 weeks as neoadjuvant therapy, then surgery and adjuvant toripalimab 3 mg/kg Q2W starting 2 ± 1weeks after surgery for 44 weeks. The primary endpoint was the pathologic response rate according to the International Neoadjuvant Melanoma Consortium recommendations. RESULTS: Between August 2019 and October 2021, 29 patients were enrolled and received treatment, of whom 24 underwent resection. The median follow-up time was 34.2 months (95% confidence interval 20.4-48.0 months). The pathologic response rate was 33.3% (8/24; 4 pathological complete responses and 4 pathological partial responses). The median event-free survival for all patients was 11.1 months (95% confidence interval 5.3-16.9 months). The median overall survival was not reached. Neoadjuvant therapy was tolerable with 8 (27.5%) grade 3-4 treatment-related adverse events and no treatment-related deaths. Tissue samples of 17 patients at baseline and after surgery were collected (5 responders and 12 nonresponders). Multiplex immunohistochemistry demonstrated a significant increase in CD3+ (P = 0.0032) and CD3+CD8+ (P = 0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy, particularly in pathological responders. CONCLUSIONS: Neoadjuvant toripalimab combined with axitinib in resectable mucosal melanoma demonstrated a promising pathologic response rate with significantly increased infiltrating CD3+ and CD3+CD8+ T cells after therapy.
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Anticorpos Monoclonais Humanizados, Melanoma, Humanos, Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico, Axitinibe/efeitos adversos, Axitinibe/uso terapêutico, Melanoma/tratamento farmacológico, Melanoma/cirurgia, Terapia Neoadjuvante/métodos, Estadiamento de NeoplasiasRESUMO
PURPOSE: This trial evaluates the addition of the PD-L1 antibody atezolizumab (ATZ) to standard-of-care fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) as a perioperative treatment for patients with resectable esophagogastric adenocarcinoma (EGA). METHODS: DANTE started as multicenter, randomized phase II trial, which was subsequently converted to a phase III trial. Here, we present the results of the phase II proportion, focusing on surgical pathology and safety outcomes on an exploratory basis. Patients with resectable EGA (≥cT2 or cN+) were assigned to either four preoperative and postoperative cycles of FLOT combined with ATZ, followed by eight cycles of ATZ maintenance (arm A) or FLOT alone (arm B). RESULTS: Two hundred ninety-five patients were randomly assigned (A, 146; B, 149) with balanced baseline characteristics between arms. Twenty-three patients (8%) had tumors with microsatellite instability (MSI), and 58% patients had tumors with a PD-L1 combined positive score (CPS) of ≥1. Surgical morbidity (A, 45%; B, 42%) and 60-day mortality (A, 3%; B, 2%) were comparable between arms. Downstaging favored arm A versus arm B (ypT0, 23% v 15% [one-sided P = .044]; ypT0-T2, 61% v 48% [one-sided P = .015]; ypN0, 68% v 54% [one-sided P = .012]). Histopathologic complete regression rates (pathologic complete response or TRG1a) were higher after FLOT plus ATZ (A, 24%; B, 15%; one-sided P = .032), and the difference was more pronounced in the PD-L1 CPS ≥10 (A, 33%; B, 12%) and MSI (A, 63%; B, 27%) subpopulations. Complete margin-free (R0) resection rates were relatively high in both arms (A, 96%; B, 95%). The incidence and severity of adverse events were similar in both groups. CONCLUSION: Within the limitations of the exploratory nature of the data, the addition of ATZ to perioperative FLOT is safe and improved postoperative stage and histopathologic regression.
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Adenocarcinoma, Anticorpos Monoclonais Humanizados, Neoplasias Esofágicas, Neoplasias Gástricas, Humanos, Adenocarcinoma/tratamento farmacológico, Adenocarcinoma/cirurgia, Adenocarcinoma/patologia, Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos, Antígeno B7-H1/uso terapêutico, Docetaxel/uso terapêutico, Neoplasias Esofágicas/tratamento farmacológico, Neoplasias Esofágicas/cirurgia, Junção Esofagogástrica/patologia, Fluoruracila/efeitos adversos, Leucovorina/efeitos adversos, Terapia Neoadjuvante/métodos, Oxaliplatina/uso terapêutico, Neoplasias Gástricas/tratamento farmacológico, Neoplasias Gástricas/cirurgia, Neoplasias Gástricas/patologiaRESUMO
PURPOSE: The Coexpression Extrapolation (COXEN) gene expression model with chemotherapy-specific scores [for methotrexate, vinblastine, adriamycin, cisplatin (ddMVAC) and gemcitabine/cisplatin (GC)] was developed to identify responders to neoadjuvant chemotherapy (NAC). We investigated RNA-based molecular subtypes as additional predictive biomarkers for NAC response, progression-free survival (PFS), and overall survival (OS) in patients treated in S1314. EXPERIMENTAL DESIGN: A total of 237 patients were randomized between four cycles of ddMVAC (51%) and GC (49%). On the basis of Affymetrix transcriptomic data, we determined subtypes using three classifiers: TCGA (k = 5), Consensus (k = 6), and MD Anderson (MDA; k = 3) and assessed subtype association with path response to NAC and determined associations with COXEN. We also tested whether each classifier contributed additional predictive power when added to a model based on predefined stratification (strat) factors (PS 0 vs. 1; T2 vs. T3, T4a). RESULTS: A total of 155 patients had gene expression results, received at least three of four cycles of NAC, and had pT-N response based on radical cystectomy. TCGA three-group classifier basal-squamous (BS)/neuronal, luminal (Lum), Lum infiltrated, and GC COXEN score yielded the largest AUCs for pT0 (0.59, P = 0.28; 0.60, P = 0.18, respectively). For downstaging (Assuntos
Terapia Neoadjuvante, Neoplasias da Bexiga Urinária, Humanos, Cisplatino/uso terapêutico, Cistectomia/métodos, Desoxicitidina/uso terapêutico, Músculos/patologia, Terapia Neoadjuvante/métodos, Invasividade Neoplásica, Intervalo Livre de Progressão, Estudos Retrospectivos, Neoplasias da Bexiga Urinária/tratamento farmacológico, Neoplasias da Bexiga Urinária/genética, Neoplasias da Bexiga Urinária/patologia
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Treatment strategies for oesophagogastric junction adenocarcinoma have not been standardized despite its poor prognosis due to differences in the incidence rates between Western countries and Asia. This randomized Phase II/III trial was initiated in June 2023 to determine which neoadjuvant chemotherapy regimen, docetaxel, oxaliplatin and S-1 or fluorouracil, oxaliplatin and docetaxel, is a more promising treatment in Phase II and confirm the superiority of neoadjuvant chemotherapy with docetaxel, oxaliplatin and S-1 or fluorouracil, oxaliplatin and docetaxel followed by surgery and postoperative chemotherapy over upfront surgery and postoperative chemotherapy in terms of overall survival in patients with Clinical Stage III or IVA oesophagogastric junction adenocarcinoma in Phase III. A total of 460 patients, including 150 patients in Phase II and 310 patients in Phase III, are planned to be enrolled from 85 hospitals in Japan over 5 years. This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031230182 (https://jrct.niph.go.jp/latest-detail/jRCTs031230182).
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Adenocarcinoma, Neoplasias Esofágicas, Neoplasias Gástricas, Humanos, Docetaxel/uso terapêutico, Oxaliplatina/uso terapêutico, Neoplasias Gástricas/patologia, Japão, Terapia Neoadjuvante/métodos, Resultado do Tratamento, Junção Esofagogástrica/patologia, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico, Neoplasias Esofágicas/patologia, Fluoruracila/uso terapêutico, Adenocarcinoma/patologia, Ensaios Clínicos Controlados Aleatórios como Assunto, Ensaios Clínicos Fase II como Assunto, Ensaios Clínicos Fase III como AssuntoRESUMO
Neoadjuvant chemotherapy (NAC) alone or combined with target therapies represents the standard of care for localized triple-negative breast cancer (TNBC). However, only a fraction of patients have a response, necessitating better understanding of the complex elements in the TNBC ecosystem that establish continuous and multidimensional interactions. Resolving such complexity requires new spatially-defined approaches. Here, we used spatial transcriptomics to investigate the multidimensional organization of TNBC at diagnosis and explore the contribution of each cell component to response to NAC. Starting from a consecutive retrospective series of TNBC cases, we designed a case-control study including 24 patients with TNBC of which 12 experienced a pathologic complete response (pCR) and 12 no-response or progression (pNR) after NAC. Over 200 regions of interest (ROI) were profiled. Our computational approaches described a model that recapitulates clinical response to therapy. The data were validated in an independent cohort of patients. Differences in the transcriptional program were detected in the tumor, stroma, and immune infiltrate comparing patients with a pCR with those with pNR. In pCR, spatial contamination between the tumor mass and the infiltrating lymphocytes was observed, sustained by a massive activation of IFN-signaling. Conversely, pNR lesions displayed increased pro-angiogenetic signaling and oxygen-based metabolism. Only modest differences were observed in the stroma, revealing a topology-based functional heterogeneity of the immune infiltrate. Thus, spatial transcriptomics provides fundamental information on the multidimensionality of TNBC and allows an effective prediction of tumor behavior. These results open new perspectives for the improvement and personalization of therapeutic approaches to TNBCs.
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Neoplasias de Mama Triplo Negativas, Humanos, Estudos de Casos e Controles, Terapia Neoadjuvante/métodos, Prognóstico, Estudos Retrospectivos, Neoplasias de Mama Triplo Negativas/tratamento farmacológico, Neoplasias de Mama Triplo Negativas/genética, FemininoRESUMO
PURPOSE: The aim of our study was to elucidate the impact of bevacizumab added to neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment and correlate the changes with the clinical outcome of the patients. EXPERIMENTAL DESIGN: IHC and multiplex immunofluorescence for lymphoid and myeloid lineage markers were performed in matched tumor samples from 23 patients with ovarian cancer enrolled in GEICO 1205/NOVA clinical study before NACT and at the time of interval cytoreductive surgery. RESULTS: Our results showed that the addition of bevacizumab to NACT plays a role mainly on lymphoid populations at the stromal compartment, detecting a significant decrease of CD4+ T cells, an increase of CD8+ T cells, and an upregulation in effector/regulatory cell ratio (CD8+/CD4+FOXP3+). None of the changes observed were detected in the intra-epithelial site in any arm (NACT or NACT-bevacizumab). No differences were found in myeloid lineage (macrophage-like). The percentage of Treg populations and effector/regulatory cell ratio in the stroma were the only two variables significantly associated with progression-free survival (PFS). CONCLUSIONS: The addition of bevacizumab to NACT did not have an impact on PFS in the GEICO 1205 study. However, at the cellular level, changes in CD4+, CD8+ lymphocyte populations, and CD8+/CD4+FOXP3 ratio have been detected only at the stromal site. On the basis of our results, we hypothesize about the existence of mechanisms of resistance that could prevent the trafficking of T-effector cells into the epithelial component of the tumor as a potential explanation for the lack of efficacy of ICI in the first-line treatment of advanced epithelial ovarian cancer. See related commentary by Soberanis Pina and Oza, p. 12.
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Terapia Neoadjuvante, Neoplasias Ovarianas, Humanos, Feminino, Carcinoma Epitelial do Ovário/tratamento farmacológico, Bevacizumab/uso terapêutico, Terapia Neoadjuvante/métodos, Microambiente Tumoral, Neoplasias Ovarianas/patologia, Fatores de Transcrição Forkhead, Quimioterapia AdjuvanteRESUMO
OBJECTIVE: This systematic review examined the diagnostic performance of magnetic resonance imaging (MRI) for assessing axillary lymph node status (ALNS) after neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science to identify relevant studies and used the QUADAS-2 tool to assess methodological quality of eligible studies. We used STATA version 12.0 to perform data pooling, heterogeneity testing, subgroup analysis, and sensitivity analysis. RESULTS: For the 21 enrolled studies, including 2875 patients, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were respectively 0.63 (95% CI: 0.53-0.72), 0.75 (95% CI: 0.68-0.81), 2.52 (95% CI: 1.98-3.19), 0.50 (95% CI: 0.39-0.63), and 5.08 (95% CI: 3.38-7.63). The AUC was 0.76 (95% CI: 0.72-0.79). I2 values of sensitivity (I2 = 94.41%) and specificity (I2 = 88.97%) were both > 50%. For the initial positive ALN patients, the pooled sensitivity and specificity were 0.64 (95% CI: 0.53-0.75) and 0.74 (95% CI: 0.64-0.82), respectively. Sensitivity analyses by focusing on studies with MRI performed post-NAC, studies using DCE-MRI, or studies with low risk of bias showed similar results to the primary analyses. CONCLUSION: MRI may have suboptimal diagnostic value in assessing ALNS after NAC for breast cancer patients. Due to the inconsistency of NAC regimens, the variability of axillary surgery, and the lack of time interval between MRI and surgery, further studies are needed to confirm our findings. CLINICAL RELEVANCE STATEMENT: Our study provided the diagnostic value of MRI in assessing axillary lymph node status after neoadjuvant chemotherapy for breast cancer patients. KEY POINTS: ⢠MRI may have suboptimal diagnostic value in assessing axillary lymph node status after NAC for general breast cancer patients. ⢠The initial axillary lymph node status has little impact on the diagnostic efficacy of MRI. ⢠The substantial heterogeneity among studies highlights the need for further studies to provide more high-quality evidence in this field.
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Neoplasias da Mama, Humanos, Feminino, Neoplasias da Mama/diagnóstico por imagem, Neoplasias da Mama/tratamento farmacológico, Neoplasias da Mama/patologia, Terapia Neoadjuvante/métodos, Metástase Linfática/patologia, Linfonodos/patologia, Imageamento por Ressonância Magnética/métodos, Axila/patologia, Biópsia de Linfonodo SentinelaRESUMO
BACKGROUND: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) following neoadjuvant chemoradiotherapy (nCRT) may not always receive resection despite the possible achievement of a pathologic complete response (pCR) being associated with superior survival benefit. We aimed to compare outcomes among ESCC patients with or without pCR and those refusing surgery. METHODS: In total, 111 medically operable, non-cervical ESCC patients after the same protocol of nCRT (platinum/5-fluorouracil plus radiation 50Gy) were prospectively enrolled between 2011 and 2021. Eighty-three of them underwent esophagectomy comprising pCR (n = 32) and non-pCR (n = 51), while 28 operable patients declined surgery (refusal-of-surgery group). Predictors and survival data were analyzed. RESULTS: In terms of esophagectomy, 38.5% (32/83) patients achieved pCR. The pCR group exhibited better pretreatment performance status than the non-pCR group (adjusted odds ratio: 0.11, 95% confidence interval: 0.03-0.58; p = 0.01). Among pCR, non-pCR, and refusal-of-surgery groups, the 5-year overall survival (OS) rates were 56%, 29% and 50% (p = 0.08) and progression-free survival (PFS) rates were 52%, 28% and 36% (p = 0.07) respectively. The pCR group had significantly better OS and PFS than the non-PCR group (adjusted hazard ratio: 2.33 and 1.93, p = 0.02 and 0.049 respectively) but not the refusal-of-surgery group. CONCLUSION: Better pretreatment performance status is associated with higher chance of pCR. Consistent with previous studies, we found attainment of pCR confers the best OS and PFS. Suboptimal OS in the refusal-of-surgery group reflects some of them would have residual disease in addition to complete remission. Further studies are needed to identify prognostic factors of pCR to select candidates who could validly decline esophagectomy.
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Neoplasias Esofágicas, Carcinoma de Células Escamosas do Esôfago, Humanos, Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico, Neoplasias Esofágicas/tratamento farmacológico, Terapia Neoadjuvante/métodos, Estudos Prospectivos, Estadiamento de Neoplasias, Esofagectomia/métodos, Resultado do Tratamento, Quimiorradioterapia, Estudos RetrospectivosRESUMO
PURPOSE: Compared to White women, there are higher mortality rates in Black/African American (BAA) women with hormone receptor-positive breast cancer (HR + BC) which may be partially due to differences in treatment resistance. We assessed factors associated with response to neoadjuvant endocrine therapy (NET). METHODS: The National Cancer Database (NCDB) was queried for women with clinical stage I-III HR + BC diagnosed 2006-2017 and treated with NET. Univariate and multivariate analyses described associations between the sample, duration of NET, and subsequent treatment response, defined by changes between clinical and pathological staging. RESULTS: The analytic sample included 9864 White and 1090 BAA women. Compared to White women, BAA women were younger, had more co-morbidities, were higher stage at presentation, and more likely to have > 24 weeks of NET. After excluding those with unknown pT/N/M, 3521 White and 365 BAA women were evaluated for NET response. On multivariate analyses, controlling for age, stage, histology, HR positivity, and duration of NET, BAA women were more likely to downstage to pT0/Tis (OR 3.0, CI 1.2-7.1) and upstage to Stage IV (OR 2.4, CI 1.002-5.6). None of the women downstaged to pT0/Tis presented with clinical stage III disease; only 2 of the women upstaged to Stage IV disease presented with clinical Stage I disease. CONCLUSION: Independent of NET duration and clinical stage at presentation, BAA women were more likely to experience both complete tumor response and progression to metastatic disease. These results suggest significant heterogeneity in tumor biology and warrant a more nuanced therapeutic approach to HR + BC.
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Neoplasias da Mama, Humanos, Feminino, Neoplasias da Mama/tratamento farmacológico, Neoplasias da Mama/patologia, Negro ou Afro-Americano, Estadiamento de Neoplasias, Terapia Neoadjuvante/métodos, BrancosRESUMO
Watch-and-wait has emerged as a new strategy for the management of rectal cancer when a complete clinical response is achieved after neoadjuvant therapy. In an attempt to standardize this new clinical approach, initiated by the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), and with the participation of the Spanish Association of Coloproctology (AECP), the Spanish Society of Pathology (SEAP), the Spanish Society of Gastrointestinal Endoscopy (SEED), the Spanish Society of Radiation Oncology (SEOR), and the Spanish Society of Medical Radiology (SERAM), we present herein a consensus on a watch-and-wait approach for the management of rectal cancer. We have focused on patient selection, the treatment schemes evaluated, the optimal timing for evaluating the clinical complete response, the oncologic outcomes after the implementation of this strategy, and a protocol for surveillance of these patients.
Assuntos
Neoplasias Retais, Conduta Expectante, Humanos, Consenso, Recidiva Local de Neoplasia/tratamento farmacológico, Neoplasias Retais/patologia, Terapia Neoadjuvante/métodos, Quimiorradioterapia/métodos, Resposta Patológica Completa, Resultado do TratamentoRESUMO
OBJECTIVE: This study aims to report the 2-year outcomes of patients with clinical stage N2-3 esophageal squamous cell carcinoma who received neoadjuvant chemotherapy and immunotherapy followed by surgery from a phase 2 NICE trial. METHODS: Eligible patients with clinical stage N2-3 esophageal squamous cell carcinoma were screened and enrolled, then treated with regimen of nab-paclitaxel (100 mg/m2, days 1, 8, 15), carboplatin (area under the curve = 5, day 1), camrelizumab (200 mg, day 1) of two 21-day cycles and esophagectomy 4 to 6 weeks after the last chemotherapy. Oncologic outcomes, recurrence patterns, overall survival (OS), and recurrence-free survival (RFS) were explored. RESULTS: From November 20, 2019, to December 22, 2020, 60 patients were recruited. After a median follow-up of 27.4 months, disease recurrence was observed in 19 (37.3%) patients, with 5 (9.8%) locoregional recurrence, 9 (17.6%) distant metastasis, and 5 (9.8%) combined recurrence. Lung was the most commonly involved metastatic site. The median time to recurrence was 10.8 months (interquartile range, 7.5-12.7 months). The 2-year OS and RFS rates were 78.1% and 67.9%, respectively. Patients who achieved major pathologic response (MPR) had a significantly greater 2-year OS rate (91.4% vs 47.7%; P < .001) and RFS rate (77.1% vs 45.9%; P = .003). On multivariable analysis, MPR was indicated as an independent prognostic factor for disease recurrence (hazard ratio, 0.39; 95% confidence interval, 0.21-0.82; P = .029). CONCLUSIONS: In patients receiving neoadjuvant chemotherapy and immunotherapy, distant metastasis remains the predominant recurrence pattern. MPR is associated with lower recurrence and better survival. Long-term results derived from randomized controlled trials are further required. TRIAL REGISTRATION NUMBER: ChiCTR1900026240.
Assuntos
Neoplasias Esofágicas, Carcinoma de Células Escamosas do Esôfago, Humanos, Carcinoma de Células Escamosas do Esôfago/terapia, Carcinoma de Células Escamosas do Esôfago/patologia, Neoplasias Esofágicas/terapia, Neoplasias Esofágicas/patologia, Terapia Neoadjuvante/efeitos adversos, Terapia Neoadjuvante/métodos, Cisplatino, Resultado do Tratamento, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico, Recidiva Local de Neoplasia/patologia, ImunoterapiaRESUMO
PURPOSE: Addition of adjuvant capecitabine improves overall survival for patients with breast cancer lacking pathologic complete response to standard-of-care neoadjuvant chemotherapy. Combining radiosensitizing capecitabine concurrent with radiation may further improve disease control, although the feasibility and tolerability of chemoradiation in this setting is unknown. This study aimed to determine the feasibility of this combination. Secondary objectives included the effect of chemoradiation on physician-reported toxicity, patient-reported skin dermatitis, and patient-reported quality of life compared with patients with breast cancer treated with adjuvant radiation. METHODS AND MATERIALS: Twenty patients with residual disease following standard neoadjuvant chemotherapy were enrolled in a prospective single-arm trial and treated with adjuvant capecitabine-based chemoradiation. Feasibility was defined as ≥75% of patients completing chemoradiation as planned. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 5.0 and the patient-reported radiation-induced skin reaction scale. Quality of life was measured using the RAND Short-Form 36-Item Health Survey. RESULTS: Eighteen patients (90%) completed chemoradiation without interruption or dose reduction. The incidence of grade ≥3 radiation dermatitis was 5% (1 of 20 patients). Patient-reported radiation dermatitis did not show a clinically meaningful difference following chemoradiation (mean increase, 55 points) compared with published reports of patients with breast cancer treated with adjuvant radiation alone (mean increase, 47 points). On the other hand, patient-reported quality of life demonstrated a clinically meaningful decline at the end of chemoradiation (mean, 46; SD, 7) compared with the reference population of patients treated with adjuvant radiation alone (mean, 50; SD, 6). CONCLUSIONS: Adjuvant chemoradiation with capecitabine is feasible and tolerable in patients with breast cancer. Although current studies using adjuvant capecitabine for residual disease following neoadjuvant chemotherapy have specified sequential treatment of capecitabine and radiation, these results support the conduct of randomized trials in this setting to investigate the efficacy of concurrent radiation with capecitabine and provide patient-reported toxicity estimates for trial design.
Assuntos
Neoplasias da Mama, Dermatite, Neoplasias Retais, Humanos, Feminino, Capecitabina, Neoplasias da Mama/tratamento farmacológico, Neoplasias da Mama/radioterapia, Terapia Neoadjuvante/efeitos adversos, Terapia Neoadjuvante/métodos, Qualidade de Vida, Estudos de Viabilidade, Estudos Prospectivos, Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos, Quimiorradioterapia Adjuvante, Quimioterapia Adjuvante/efeitos adversos, Quimioterapia Adjuvante/métodos, Fluoruracila, Neoplasias Retais/patologiaRESUMO
OBJECTIVE: To identify which dynamic contrast-enhanced (DCE-)MRI features best predict histological response to neoadjuvant chemotherapy in patients with an osteosarcoma. METHODS: Patients with osteosarcoma who underwent DCE-MRI before and after neoadjuvant chemotherapy prior to resection were retrospectively included at two different centers. Data from the center with the larger cohort (training cohort) was used to identify which method for region-of-interest selection (whole slab or focal area method) and which change in DCE-MRI features (time to enhancement, wash-in rate, maximum relative enhancement and area under the curve) gave the most accurate prediction of histological response. Models were created using logistic regression and cross-validated. The most accurate model was then externally validated using data from the other center (test cohort). RESULTS: Fifty-five (27 poor response) and 30 (19 poor response) patients were included in training and test cohorts, respectively. Intraclass correlation coefficient of relative DCE-MRI features ranged 0.81-0.97 with the whole slab and 0.57-0.85 with the focal area segmentation method. Poor histological response was best predicted with the whole slab segmentation method using a single feature threshold, relative wash-in rate <2.3. Mean accuracy was 0.85 (95%CI: 0.75-0.95), and area under the receiver operating characteristic curve (AUC-index) was 0.93 (95%CI: 0.86-1.00). In external validation, accuracy and AUC-index were 0.80 and 0.80. CONCLUSION: In this study, a relative wash-in rate of <2.3 determined with the whole slab segmentation method predicted histological response to neoadjuvant chemotherapy in osteosarcoma. Consistent performance was observed in an external test cohort.
Assuntos
Neoplasias Ósseas, Osteossarcoma, Humanos, Terapia Neoadjuvante/métodos, Estudos Retrospectivos, Resultado do Tratamento, Imageamento por Ressonância Magnética/métodos, Osteossarcoma/diagnóstico por imagem, Osteossarcoma/tratamento farmacológico, Neoplasias Ósseas/diagnóstico por imagem, Neoplasias Ósseas/tratamento farmacológicoRESUMO
Pancreatic cancer is a malignant disease with a dismal prognosis. While neoadjuvant therapy has shown promise in the treatment of pancreatic cancer, its role remains a subject of controversy among physicians. We aimed to evaluate the benefits of neoadjuvant therapy in patients with resectable and borderline resectable pancreatic cancer. Eligible studies were identified from MEDLINE, Embase, Cochrane Library, and Web of Science. Studies comparing neoadjuvant therapy with upfront surgery (with or without adjuvant therapy) in resectable and borderline resectable pancreatic cancer were included. The primary endpoint assessed was overall survival. A total of 10,022 studies were identified, and the meta-analysis finally enrolled 50 revealed studies. The meta-analysis suggested that neoadjuvant therapy significantly improved the overall survival (HR 0.74, p < 0.001) and recurrence-free survival (HR 0.75, p = 0.006) compared to the upfront surgery approach. Furthermore, neoadjuvant therapy leads to favorable postoperative outcomes, with an enhanced R0 resection rate (OR 1.90, p < 0.001) and reduced lymph node metastasis (OR 0.36, p < 0.001) and perineural invasion (OR 0.42, p < 0.001), although it is associated with a reduced resection rate (OR 0.42, p < 0.001). In addition, patients treated with neoadjuvant therapy experience superior survival benefits compared to those undergoing adjuvant therapy (HR 0.87, p = 0.019). These results are further corroborated by the subgroup analysis of randomized controlled trials. Neoadjuvant therapy has the potential to provide survival benefits and improve postoperative long-term outcomes for patients with resectable and borderline resectable pancreatic cancer. However, to validate and reinforce these findings, further well-designed and large trials are required.
Assuntos
Adenocarcinoma, Neoplasias Pancreáticas, Humanos, Terapia Neoadjuvante/métodos, Neoplasias Pancreáticas/tratamento farmacológico, Neoplasias Pancreáticas/cirurgia, Terapia Combinada, PrognósticoRESUMO
OBJECTIVE: To use a customized smartphone application to prospectively measure QOL and the real-time patient experience during neoadjuvant therapy (NT). BACKGROUND: NT is increasingly used for patients with localized gastrointestinal (GI) cancers. There is little data assessing patient experience and quality of life (QOL) during NT for GI cancers. METHODS: Patients with GI cancers receiving NT were instructed on using a customized smartphone application through which the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, a validated measure of health-related QOL, was administered at baseline, every 30 days, and at the completion of NT. Participants also tracked their moods and symptoms and used free-text journaling functionalities in the application. Mean overall and subsection health-related QOL scores were calculated during NT. RESULTS: Among 104 enrolled patients, the mean age was 60.5 ± 11.5 years and 55% were males. Common cancer diagnoses were colorectal (40%), pancreatic (37%), and esophageal (15%). Mean overall FACT-G scores did not change during NT ( P = 0.987). While functional well-being scores were consistently the lowest and social well-being scores the highest, FACT subscores similarly did not change during NT (all P > 0.01). The most common symptoms reported during NT were fatigue, insomnia, and anxiety (39.3%, 34.5%, and 28.3% of patient entries, respectively). Qualitative analysis of free-text journaling entries identified anxiety, fear, and frustration as the most common themes, but also the importance of social support systems and confidence in health care providers. CONCLUSIONS: While patient symptom burden remains high, results of this prospective cohort study suggest QOL is maintained during NT for localized GI cancers.
