Schaner Philip E, Williams Benjamin B, Chen Eunice Y, Pettus Jason R, Schreiber Wilson A, Kmiec Maciej M, Jarvis Lesley A, Pastel David A, Zuurbier Rebecca A, DiFlorio-Alexander Roberta M, Paydarfar Joseph A, Gosselin Benoit J, Barth Richard J, Rosenkranz Kari M, Petryakov Sergey V, Hou Huagang, Tse Dan, Pletnev Alexandre, Flood Ann Barry, Wood Victoria A, Hebert Kendra A, Mosher Robyn E, Demidenko Eugene, Swartz Harold M, Kuppusamy Periannan
Department of Medicine, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth College, and Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States.
Department of Radiology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth College, and Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States.
Front Oncol. 2021 Oct 1;11:743256. doi: 10.3389/fonc.2021.743256. eCollection 2021.
The overall objective of this clinical study was to validate an implantable oxygen sensor, called the 'OxyChip', as a clinically feasible technology that would allow individualized tumor-oxygen assessments in cancer patients prior to and during hypoxia-modification interventions such as hyperoxygen breathing.
Patients with any solid tumor at ≤3-cm depth from the skin-surface scheduled to undergo surgical resection (with or without neoadjuvant therapy) were considered eligible for the study. The OxyChip was implanted in the tumor and subsequently removed during standard-of-care surgery. Partial pressure of oxygen (pO) at the implant location was assessed using electron paramagnetic resonance (EPR) oximetry.
Twenty-three cancer patients underwent OxyChip implantation in their tumors. Six patients received neoadjuvant therapy while the OxyChip was implanted. Median implant duration was 30 days (range 4-128 days). Forty-five successful oxygen measurements were made in 15 patients. Baseline pO values were variable with overall median 15.7 mmHg (range 0.6-73.1 mmHg); 33% of the values were below 10 mmHg. After hyperoxygenation, the overall median pO was 31.8 mmHg (range 1.5-144.6 mmHg). In 83% of the measurements, there was a statistically significant (p ≤ 0.05) response to hyperoxygenation.
Measurement of baseline pO and response to hyperoxygenation using EPR oximetry with the OxyChip is clinically feasible in a variety of tumor types. Tumor oxygen at baseline differed significantly among patients. Although most tumors responded to a hyperoxygenation intervention, some were non-responders. These data demonstrated the need for individualized assessment of tumor oxygenation in the context of planned hyperoxygenation interventions to optimize clinical outcomes.
本临床研究的总体目标是验证一种名为“氧芯片”的可植入式氧传感器，作为一种临床可行的技术，能够在诸如高氧呼吸等低氧修正干预之前及期间，对癌症患者进行个体化的肿瘤氧评估。
计划接受手术切除（无论有无新辅助治疗）且肿瘤距皮肤表面深度≤3厘米的任何实体瘤患者被认为符合本研究条件。将氧芯片植入肿瘤，随后在标准治疗手术期间取出。使用电子顺磁共振（EPR）血氧测定法评估植入部位的氧分压（pO）。
23名癌症患者在其肿瘤中植入了氧芯片。6名患者在植入氧芯片时接受了新辅助治疗。植入的中位持续时间为30天（范围4 - 128天）。15名患者进行了45次成功的氧测量。基线pO值各不相同，总体中位值为15.7 mmHg（范围0.6 - 73.1 mmHg）；33%的值低于10 mmHg。高氧治疗后，总体中位pO为31.8 mmHg（范围1.5 - 144.6 mmHg）。在83%的测量中，对高氧治疗有统计学显著（p≤0.05）反应。
使用氧芯片通过EPR血氧测定法测量基线pO以及对高氧治疗的反应在多种肿瘤类型中临床可行。患者之间基线时的肿瘤氧含量差异显著。虽然大多数肿瘤对高氧治疗有反应，但有些无反应。这些数据表明，在计划进行高氧治疗干预以优化临床结果的背景下，需要对肿瘤氧合进行个体化评估。
