J Clin Oncol 2021 Jun 02
Randomized Phase II Study of PET Response-Adapted Combined Modality Therapy for Esophageal Cancer: Mature Results of the CALGB 80803 (Alliance) Trial.
Abstract
Purpose
To evaluate the use of early assessment of chemotherapy responsiveness by positron emission tomography (PET) imaging to tailor therapy in patients with esophageal and esophagogastric junction adenocarcinoma.
Methods
After baseline PET, patients were randomly assigned to an induction chemotherapy regimen: modified oxaliplatin, leucovorin, and fluorouracil (FOLFOX) or carboplatin-paclitaxel (CP). Repeat PET was performed after induction; change in maximum standardized uptake value (SUV) from baseline was assessed. PET nonresponders (< 35% decrease in SUV) crossed over to the alternative chemotherapy during chemoradiation (50.4 Gy/28 fractions). PET responders (≥ 35% decrease in SUV) continued on the same chemotherapy during chemoradiation. Patients underwent surgery at 6 weeks postchemoradiation. Primary end point was pathologic complete response (pCR) rate in nonresponders after switching chemotherapy.
Results
Two hundred forty-one eligible patients received Protocol treatment, of whom 225 had an evaluable repeat PET. The pCR rates for PET nonresponders after induction FOLFOX who crossed over to CP (n = 39) or after induction CP who changed to FOLFOX (n = 50) was 18.0% (95% CI, 7.5 to 33.5) and 20% (95% CI, 10 to 33.7), respectively. The pCR rate in responders who received induction FOLFOX was 40.3% (95% CI, 28.9 to 52.5) and 14.1% (95% CI, 6.6 to 25.0) in responders to CP. With a median follow-up of 5.2 years, median overall survival was 48.8 months (95% CI, 33.2 months to not estimable) for PET responders and 27.4 months (95% CI, 19.4 months to not estimable) for nonresponders. For induction FOLFOX patients who were PET responders, median survival was not reached.
Conclusion
Early response assessment using PET imaging as a biomarker to individualize therapy for patients with esophageal and esophagogastric junction adenocarcinoma was effective, improving pCR rates in PET nonresponders. PET responders to induction FOLFOX who continued on FOLFOX during chemoradiation achieved a promising 5-year overall survival of 53%.
Related Questions
Are there patients for whom CROSS followed by surgery and adjuvant nivolumab should still be considered, following data from MATTERHORN and ESOPEC?
ESOPEC does not invalidate CROSS—it redefines the preferred option for fit patients; in the real world, not every patient will be able to tolerate FLOT or d-FLOT: Yes. Despite the emergence of perioperative FLOT-based strategies from ESOPEC and MATTERHORN, CROSS, followed by surgery and adjuvant niv...
In a patient with gastroesophageal adenocarcinoma treated with neoadjuvant chemoimmunotherapy who had a good response but is unable to undergo surgery, how would you approach radiation therapy?
As the ARTDECO study did not show a difference in local control between 50.4 Gy and 61.6 Gy (given with carbo/taxol, but FOLFOX is also an option per PRODIGE5, depending on chemotherapy used as part of the initial chemo-IO), I would suggest 50.4 Gy.
For a patient with T3N1M0 esophageal adenocarcinoma, who suffered esophageal perforation necessitating metallic stent placement, would you favor a neoadjuvant chemoradiation or perioperative chemotherapy approach?
In situations of esophageal perforation, the main concern will be the dissemination of disease particularly in the thoracic cavity, i.e. pleura. Therefore, I favor a systemic therapy approach upfront. Should the patient have a good response to systemic therapy, then chemoradiation could be considere...
Does an esophageal stent impact your radiation treatment plan for a patient with non-metastatic GE junction adenocarcinoma?
While the presence of a stent might not directly affect my radiation dose and volumes, due to numerous other considerations, it would certainly affect my overall treatment plan. I highly encourage avoiding a stent in the setting of radiation due to toxicity concerns in addition to the complications ...
How do you dose FOLFOX when given with concurrent chemoradiation in esophageal adenocarcinoma?
I don’t use FOLFOX within this setting.
How would you manage a patient with synchronous locally advanced rectal adenocarcinoma (T3N2) and a large T2N0 adenocarcinoma of mid and distal esophagus?
A tough situation no doubt. Def need an MDT agreement with medical oncology and surgery. The patient should be evaluated for surgical (especially esophageal resectability). I am going to try to be creative here : I would vote 5x5 to rectal mass then get on mFOLFOX6 based chemo per CALGB 80803 trial...
How would you treat a patient with T4N1M0 GEJ adenocarcinoma with local progression after concurrent chemoRT who still has resectable disease?
This is a tricky but thankfully rare scenario.My answer depends on the nature of the local progression. The more favorable situation involves local persistence of the primary tumor with a modest increase in locoregional lymph nodes. This situation would essentially represent a lack of response to ch...
Based on the results of CALGB 80803, would you consider induction and/or concurrent FOLFOX in neoadjuvant treatment of esophageal adenocarcinoma?
Great question. The CROSS regimen has been our standard for resectable GE junction and esophagus adenocarcinomas, but the data from the CALGB 80803 study are compelling.For some patients with questionable disease resectability, usually due to extensive nodal involvement, we have been giving “inducti...