ABSTRACT
Background: Induction FOLFOX followed by PET-directed CRT prior to surgery demonstrated positive results in the CALGB 80803 study. We investigated the safety and efficacy of adding D, an anti-PD-L1 antibody, to PET-directed CRT. Methods: Patients (pts) with locally advanced esophageal/GEJ adenocarcinoma were enrolled. Pts received 2 cycles of mFOLFOX6 prior to repeat PET/CT. PET responders (≥35% reduction in SUV (PETr)) received 5-FU/capecitabine and oxaliplatin with RT to 50.4Gy, while induction PET non-responders (PETnr) received carboplatin/paclitaxel with RT. All Pts received D 1,500 mg q4W ×2 starting 2 weeks prior to CRT. Esophagectomy was planned 6-8 weeks after CRT. Pts with R0 resections received adjuvant D 1,500mg q4W ×6. The primary endpoint was the pathologic complete response (pCR) rate. Results: 36 pts were enrolled. Clinical ≥T3 disease was seen in 32 pts (88.9%, cT4 = 3) and ≥N1 in 23 (63.9%) pts. PD-L1 CPS was ≥1 in 25 (71.4%) of 35 tested with 14 (40%) ≥5. Microsatellite instability (MSI) was identified in 3 (8.3%) pts. 25 (70%) pts were PETr. Preop treatment was well tolerated with no new safety signals. Three pts had disease progression prior to surgery. pCR was identified in 8 (22.2%) pts and 22 (64.7%) had major pathologic response (MPR;ypTanyN0 + ≥90% response). Those with MSI tumors had ≥90% treatment response (1 pCR, 1: ypT1aN0 99% response, 1: ypT2N0, 90% response). 17 (73.9%) of 23 cN+ pts had ypN0 disease. MPR was associated with PD-L1 ≥1 (p = 0.03) and with a higher tumor mutational burden (TMB;p = 0.016) on MSK-IMPACT testing. Adjuvant D was commenced in 27 pts, with a median number of 6 cycles. Early discontinuation was due to risks of visits due to COVID19 (4, 15%), progressive disease (3, 11%), late surgical complications (2, 7%) and immune toxicity (1, 4%). With a median follow-up of 30 months, OS rates were 92% [95%CI: 83%-100%] and 85 % [95%CI: 74%-98%] at 12 and 24 months post induction. 12 and 24-month PFS rates were 81% [95%CI: 69%-95%] and 71% [95%CI: 58%-88%] respectively. In the 33 operated pts, 12 and 24-month disease free survival was 82% [95%CI: 70%-96%] and 78% [95%CI: 65%-94%], respectively. In addition to SUV on PET, total lesion glycolysis (TLG) was correlated with pathologic response. In cases with borderline change in SUV, TLG could predict response to treatment. One PETnr with 30.8% reduction in SUV had 88.1% reduction in TLG and pCR. Conversely, a PETr (-36.3%) who had an increase in TLG (39.3%) had only 40% treatment response on pathology. Conclusions: The addition of D to induction FOLFOX and PETdirected CRT prior to surgery is safe and appears effective with a high rate of pathologic response, as well as encouraging survival data. PD-L1 CPS≥1 and higher TMB may be associated with MPR. TLG is a novel PET variable that should be studied prospectively. Additional correlatives and comparison to a cohort treated with standard PET-directed CRT will be presented.
ABSTRACT
Introduction: UBT is the most accurate non-invasive test for H.pylori infection. The orally given urea, labelled with C13, is hydrolysed by the enzyme urease of H.pylori and C13O2 is measured expired in breath. UBT was our gold standard diagnostic test for H.pylori. This practice changed abruptly in March 2020, when our first wave of coronavirus -2 (SARS-CoV-2) started. UBT carries the risk of contamination by SARS-CoV-2 in the aerosol droplets generated by exhaled air. The British Society of Gastroenterology guideline at that time graded UBT as Aerosol Generating Procedure and therefore at high risk for transmission. Only emergency gastroenterology high risk procedures were recommended during restrictions which effectively terminated our standard UBT service. To maintain a non-invasive diagnostic option we developed a novel virtual test. C13 UBT At Home, is performed by patients at home with step by step instructions involving live video conference interaction between the patients and technicians. Aims & Methods: To determine the acceptability and the accuracy of the novel C13 UBT At Home service. Patients on a UBT waiting list were contacted and invited to undergo the alternative virtual breath test. Willing participants were pre assessed over phone to explain the process. Technical aspects (internet, smart phone or laptop requirements), navigation through the video call system attendanywhere and routine clinical parameters including PPI and antibiotic use were discussed. Suitable patients collected a Home UBT kit (Patient information sheet, test documentation, pre and post collection tubes, collection straw, urea tablet and feedback questionnaire) from a drop off point up to a week prior to their scheduled appointment. The test was performed as standard by the patient at home with live interaction for all active steps. The 20 minute rest between samples 1 and 2 collection was offline which allowed technicians to do concurrent cases. Patients were requested to fill in a feedback questionnaire after the test and to return it with the samples to the drop off point within 48 hours for analysis. The questionnaire included 6 questions covering pre procedure, procedure and post procedure domains. In addition to patient satisfaction, positivity rate, sample error rate and activity numbers were compared between UBT at home and a standard UBT cohort which was reinstated in 2021. Results: 300 patients were enrolled, mean age 41 years (range 7-85), 177 female (59%). Overall response rate was 96% (288), 96% (285) rated the entire UBT at home process as either excellent or good. All other parameters except connection to the hospital video call system, which was subject to external factors were also rated excellent/good by >90%. Accuracy between UBT tests was similar: positivity rate 23% (69/299) versus 22% (74/326), sample error rate 0.33% (1/300) versus 0.6% (2/326) for the UBT at home and standard tests respectively. Currently 3 of every 4 UBT's is now virtual despite reduced restrictions. Conclusion: UBT at home is possible and acceptable to patients with equivalent accuracy to standard UBT and should be continued to improve patient choice and satisfaction.