Dataset Information

Adaptive Neoadjuvant Chemotherapy Guided by (18)F-FDG PET in Resectable Non-Small Cell Lung Cancers: The NEOSCAN Trial.

ABSTRACT: Although perioperative chemotherapy improves survival in patients with resectable lung cancers, systemic recurrence remains common. Neoadjuvant chemotherapy permits response assessment and an opportunity to switch treatment regimens. Response measured by fludeoxyglucose ((18)F-FDG) positron emission tomography (PET) correlates with clinical outcomes better than computed tomography (CT) does. This trial assessed PET-measured response rate to alternative chemotherapy in patients with a suboptimal PET response after two cycles of neoadjuvant chemotherapy.This phase II study enrolled patients with resectable stage IB-IIIA lung cancers (primary tumor ? 2 cm and peak standard uptake value [SUVpeak] ? 4.5). Patients had a pretreatment (18)F-FDG PET/CT scan before two cycles of cisplatin (or carboplatin) plus gemcitabine (squamous cell carcinoma) or pemetrexed (adenocarcinoma) and then a repeat PET/CT scan. If SUVpeak in the primary tumor decreased by at least 35%, patients continued the initial chemotherapy. Individuals with less than a 35% PET response were switched to vinorelbine plus docetaxel. Postoperative radiotherapy was recommended to all patients with positive N2 nodes. A Simon's optimal two-stage design was used to evaluate the primary end point of a PET Response in Solid Tumors-defined response rate to vinorelbine plus docetaxel in previously nonresponding patients.Forty patients were enrolled. Fifteen patients (38% [95% confidence interval: 38-53]) had less than a 35% decrease in SUVpeak, and 13 received vinorelbine plus docetaxel. The study met its primary end point with 10 of 15 PET metabolic responses to alternate therapy (67%). Chemotherapy toxicities never precluded surgical exploration.Utilizing (18)F-FDG PET/CT to assess response and change preoperative chemotherapy in nonresponding patients can improve radiographic measures of response. This adaptive approach can also be used to test new drugs, attempting to optimize perioperative chemotherapy to achieve better long-term outcomes.

SUBMITTER: Chaft JE

PROVIDER: S-EPMC4808609 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Adaptive Neoadjuvant Chemotherapy Guided by (18)F-FDG PET in Resectable Non-Small Cell Lung Cancers: The NEOSCAN Trial.

Chaft Jamie E JE Dunphy Mark M Naidoo Jarushka J Travis William D WD Hellmann Matthew M Woo Kaitlin K Downey Robert R Rusch Valerie V Ginsberg Michelle S MS Azzoli Christopher G CG Kris Mark G MG

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20151225 4

<h4>Introduction</h4>Although perioperative chemotherapy improves survival in patients with resectable lung cancers, systemic recurrence remains common. Neoadjuvant chemotherapy permits response assessment and an opportunity to switch treatment regimens. Response measured by fludeoxyglucose ((18)F-FDG) positron emission tomography (PET) correlates with clinical outcomes better than computed tomography (CT) does. This trial assessed PET-measured response rate to alternative chemotherapy in patien ...[more]

PMID: 26724474

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Project description:BackgroundThe purpose of this study was to investigate the value of 18 [F]-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) in tailoring axillary surgery by predicting nodal response among patients with node-positive breast cancer after neoadjuvant chemotherapy (NAC).MethodsOne hundred thirty-three patients with breast cancer with biopsy-confirmed nodal metastasis were prospectively enrolled. 18 F-FDG PET/CT scan was performed before NAC (a second one after two cycles with baseline maximum standardized uptake value [SUVmax ] ≥2.5), and a subset of patients underwent targeted axillary dissection (TAD). All the patients underwent axillary lymph node dissection (ALND). The accuracy was calculated by a comparison with the final pathologic results.ResultsWith the cutoff value of 2.5 for baseline SUVmax and 78.4% for change in SUVmax , sequential 18 F-FDG PET/CT scans demonstrated a sensitivity of 79.0% and specificity of 71.4% in predicting axillary pathologic complete response with an area under curve (AUC) of 0.75 (95% confidence interval, 0.65-0.84). Explorative subgroup analyses indicated little value for estrogen receptor (ER)-negative, human epidermal growth factor receptor 2 (HER2)-positive patients (AUC, 0.55; sensitivity, 56.5%; specificity, 50.0%). Application of 18 F-FDG PET/CT could spare 19 patients from supplementary ALNDs and reduce one of three false-negative cases in TAD among the remaining patients without ER-negative/HER2-positive subtype.ConclusionApplication of the subtype-guided 18 F-FDG PET/CT could accurately predict nodal response and aid in tailoring axillary surgery among patients with node-positive breast cancer after NAC, which includes identifying candidates appropriate for TAD or directly proceeding to ALND. This approach might help to avoid false-negative events in TAD.Implications for practiceThis feasibility study showed that 18 [F]-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) could accurately predict nodal response after neoadjuvant chemotherapy (NAC) among patients with breast cancer with initial nodal metastasis except in estrogen receptor-negative, human epidermal growth factor receptor 2-positive subtype. Furthermore, the incorporation of 18 F-FDG PET/CT can tailor subsequent axillary surgery by identifying patients with residual nodal disease, thus sparing those patients supplementary axillary lymph node dissection. Finally, we have proposed a possibly feasible flowchart involving 18 F-FDG PET/CT that might be applied in post-NAC axillary evaluation.

Project description:PurposeTo develop a comprehensive PET radiomics model to predict the pathological response after neoadjuvant toripalimab with chemotherapy in resectable stage III non-small-cell lung cancer (NSCLC) patients.MethodsStage III NSCLC patients who received three cycles of neoadjuvant toripalimab with chemotherapy and underwent 18F-FDG PET/CT were enrolled. Baseline 18F-FDG PET/CT was performed before treatment, and preoperative 18F-FDG PET/CT was performed three weeks after the completion of neoadjuvant treatment. Surgical resection was performed 4-5 weeks after the completion of neoadjuvant treatment. Standardized uptake value (SUV) statistics features and radiomics features were derived from baseline and preoperative PET images. Delta features were derived. The radiologic response and metabolic response were assessed by iRECIST and iPERCIST, respectively. The correlations between PD-L1 expression, driver-gene status, peripheral blood biomarkers, and the pathological responses (complete pathological response [CPR]; major pathological response [MPR]) were assessed. Associations between PET features and pathological responses were evaluated by logistic regression.ResultsThirty patients underwent surgery and 29 of them performed preoperative PET/CT. Twenty patients achieved MPR and 16 of them achieved CPR. In univariate analysis, five SUV statistics features and two radiomics features were significantly associated with pathological responses. In multi-variate analysis, SUVmax, SUVpeak, SULpeak, and End-PET-GLDM-LargeDependenceHighGrayLevelEmphasis (End-GLDM-LDHGLE) were independently associated with CPR. SUVpeak and SULpeak performed better than SUVmax and SULmax for MPR prediction. No significant correlation, neither between the radiologic response and the pathological response, nor among PD-L1, driver gene status, and baseline PET features was found. Inflammatory response biomarkers by peripheral blood showed no difference in different treatment responses.ConclusionThe logistic regression model using comprehensive PET features contributed to predicting the pathological response after neoadjuvant toripalimab with chemotherapy in resectable stage III NSCLC patients.

Project description:PURPOSE:The histological response to neoadjuvant chemotherapy is an important prognostic factor in patients with osteosarcoma (OS) and Ewing sarcoma (EWS). The aim of this study was to assess baseline primary tumour FDG uptake on PET/CT, and serum values of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), to establish whether these factors are correlated with tumour necrosis and prognosis. METHODS:Patients treated between 2009 and 2014 for localized EWS and OS, who underwent FDG PET/CT as part of their staging work-up, were included. The relationships between primary tumour SUVmax at baseline (SUV1), SUVmax after induction chemotherapy (SUV2), metabolic response calculated as [(SUV1?-?SUV2)/SUV1)]?×?100, LDH and ALP and tumour response/survival were analysed. A good response (GR) was defined as tumour necrosis >90 % in patients with OS, and grade II-III Picci necrosis (persitence of microscopic foci only or no viable tumor) in patients with Ewing sarcoma. RESULTS:The study included 77 patients, 45 with EWS and 32 with OS. A good histological response was achieved in 53 % of EWS patients, and 41 % of OS patients. The 3-year event-free survival (EFS) was 57 % in EWS patients and 48 % OS patients. The median SUV1 was 5.6 (range 0?-?17) in EWS patients and 7.9 (range 0?-?24) in OS patients (p?=?0.006). In EWS patients the GR rate was 30 % in those with a high SUV1 (?6) and 72 % in those with a lower SUV1 (p?=?0.0004), and in OS patients the GR rate was 29 % in those with SUV1 ?6 and 64 % in those with a lower SUV1 (p?=?0.05). In the univariate analysis the 3-year EFS was significantly better in patients with a low ALP level (59 %) than in those with a high ALP level (22 %, p?=?0.02) and in patients with a low LDH level (62 %) than in those with a high LDH level (37 %, p?=?0.004). In EWS patients the 3-year EFS was 37 % in those with a high SUV1 and 75 % in those with a low SUV1 (p?=?0.004), and in OS patients the 3-year EFS was 32 % in those with a high SUV1 and 66 % in those with a low SUV1 (p?=?0.1). Histology, age and gender were not associated with survival. In the multivariate analysis, SUV1 was the only independent pretreatment prognostic factor to retain statistical significance (p?=?0.017). SUV2 was assessed in 25 EWS patients: the median SUV2 was 1.9 (range 1?-?8). The GR rate was 20 % in patients with a high SUV2, and 67 % in those with a low SUV2 (p?=?0.02). A good metabolic response (SUV reduction of ?55 %) was associated with a 3-year EFS of 80 % and a poor metabolic response with a 3-year EFS of 20 % (p?=?0.05). In the OS patients the median SUV2 was 2.7 (range 0?-?4.5). Neither SUV2 nor the metabolic response was associated with outcome in OS patients. CONCLUSION:FDG PET/CT is a useful and noninvasive tool for identifying patients who are more likely to be resistant to chemotherapy. If this finding is confirmed in a larger series, SUV1, SUV2 and metabolic response could be proposed as factors for stratifying EWS patients to identify those with high-grade localized bone EWS who would benefit from risk-adapted induction chemotherapy.

Dataset Information

Adaptive Neoadjuvant Chemotherapy Guided by (18)F-FDG PET in Resectable Non-Small Cell Lung Cancers: The NEOSCAN Trial.

Publications

Adaptive Neoadjuvant Chemotherapy Guided by (18)F-FDG PET in Resectable Non-Small Cell Lung Cancers: The NEOSCAN Trial.

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