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

Abstract

Introduction Although perioperative chemotherapy improves survival in patients with resectable lung cancers, systemic recurrence remains common. Neoadjuvant chemotherapy permits response assessment and opportunity to switch treatment regimens. Response measured by fluorodeoxyglucose PET correlates better than CT with clinical outcomes. The NEOSCAN trial assessed PET-measured response rate to alternative chemotherapy in patients with a suboptimal PET response after 2 cycles of neoadjuvant chemotherapy. Methods This phase 2 study enrolled patients with resectable stage IB-IIIA lung cancers (primary tumor ≥2 cm and SUVpeak≥4.5). Patients had a pretreatment FDG PET/CT before 2 cycles of cisplatin (or carboplatin) + gemcitabine (squamous) or pemetrexed (adenocarcinomas) then repeat PET/CT. If SUVpeak in the primary tumor decreased by ≥35%, patients continued the initial chemotherapy. Individuals with <35% PET response were switched to vinorelbine + docetaxel. Post operative radiotherapy was recommended to all patients with positive N2 nodes. A Simon-optimal two stage design was used to evaluate the primary endpoint of a PERCIST-defined response rate to vinorelbine + docetaxel in previously non-responding patients. Results 40 patients were enrolled. 15 patients (38%, 95% CI: 38–53%) had <35% decrease in SUVpeak and 13 received vinorelbine + docetaxel. The study met its primary endpoint with 10/15 (67%) PET metabolic responses to alternate therapy. Chemotherapy toxicities never precluded surgical exploration. Conclusions Utilizing FDG PET/CT to assess response and change preoperative chemotherapy in non-responding 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.

Neoadjuvant Chemoradiotherapy vesus Chemotherapy alone Followed by Surgery for Resectable Stage III Non-Small-Cell Lung Cancer: a Meta-Analysis

“…Unanswered questions remain about definitive chemoradiotherapy, including the optimal chemotherapy agents; dose, duration, density of chemotherapy 26 , radiation fractionation and radiation dose 27 28 29 30 . However, we were not sure tumor cells would be more sensitive to radiotherapy or chemotherapy when diagnosed, especially for squamous cell carcinoma patients 31 , best modality for assessing response in advanced disease utilizing 18F-FDG PET/CT has been testing 32 , studies on identifying markers to predict the response to CRT should be pursued 33 34 , moreover, strategies to select patients for the most appropriate therapy according to the molecular profile of individual tumors could contribute to further improvements in treatment outcome. In conclusion, clinicians needed to investigate the higher quality of trials combined with the histopathological type and genotyping of lung cancer, and probe the best method of treatment for resectable Stage III Non-Small-Cell Lung Cancer.…”

Current Status and Future Perspectives on Neoadjuvant Therapy in Lung Cancer

“…Changes in primary tumors provide a reliable way to assess the impact of neoadjuvant treatment on an individual's tumor and presents an opportunity to change the induction regimen before surgery. 19 Neoadjuvant approaches can more rapidly translate clinical research findings to early drug approvals. The use of pCR for accelerated approval of HER2-targeted therapy for breast cancer shows that the neoadjuvant setting has the potential to expedite the development of new therapies.…”

“…[53][54][55][56] A PET adaptive study has been performed, assigning switch therapy in patients who do not respond by a predefined SUV criterion. 19 Whereas PET response to neoadjuvant therapy may be associated with improved outcomes, no definition of PET response has been universally adopted. As these functional imaging studies are performed preand post-therapy as part of routine care and in research protocols, efforts should be made to uniformly collect and analyze this data.…”

Before or After: Evolving Neoadjuvant Approaches to Locally Advanced Non-Small Cell Lung Cancer

“…In fact, a 35% decrease of FDG uptake after one cycle of neoadjuvant chemotherapy discriminated responders from non-responders ( 83 ). Taking these findings further, a recent phase II study assessed the timing of treatment switch to optimize response rates ( 84 ). In this phase II study, 40 patients with resectable stage IB to IIIA NSCLC received neoadjuvant chemotherapy with a platinum-based doublet (carboplatin or cisplatin plus gemcitabine or pemetrexed).…”