CORR Insights®: Transcutaneous Oximetry Does Not Reliably Predict Wound-healing Complications in Preoperatively Radiated Soft Tissue Sarcoma

Where Are We Now?

Wound dehiscence and infection are the nemesis of every surgeon, regardless of the era of practice, level of experience, or specialty [6]. Today, the problem of surgical wound healing is far from solved, particularly in oncology, despite increased advancements in basic science [4].

Wound complications and infection in radiated tissue are of great relevance across all surgical oncology specialties, including musculoskeletal oncology. Although radiation-induced tissue damage and associated changes in capillary density have been recognized since shortly after the discovery of radiography at the end of the 19th century [12], radiotherapy remains a key component of multidisciplinary cancer treatment.

In soft tissue sarcomas, the importance of wound complications after radiation cannot be overemphasized because of several interacting issues that all may result in harm to the patient, namely: (1) a high incidence of wound complications in lower extremity surgery [11]; (2) management is difficult and may be characterized by prolonged and exhausting treatment, resulting in multiple hospitalizations and surgical procedures; (3) treatment of wound complications may delay subsequent chemotherapy (if chemotherapy is indicated) and negatively affect prognosis; and (4) there is a financial burden for the patient associated with the treatment (which is magnified if complications or persistent disability arise as a result of it).

In the current study, Nystrom et al. [9] prospectively assessed skin oxygenation in patients undergoing surgery for lower extremity soft tissue sarcoma after preoperative radiation at three timepoints (before radiation, right after radiation, and within 24 hours before the surgery), which were selected based on the rationale that radiotherapy would predictably interfere in a time-dependent fashion with skin oxygenation. They found no benefit from measurement of transcutaneous oxygen tension (TcO₂) in anticipating wound complications, using a TcO₂ reading with a cutoff of 25 mmHg and as a continuous variable. They also found no correlation between wound complications and increased skin oxygenation between the end of radiation and the time of surgery.

Despite the obvious relationship between hypoxia and wound breakdown, numerous variables may have contributed to this null result. As pointed out by the authors [9], transcutaneous oximetry provides limited focal sampling and, despite the use of multiple leads, only a small portion of the wound surface is assessed. In addition, even with the standardized radiation regimen of 50 Gy in 25 fractions they used for all patients, variability in tumor volume and anatomic compartment may cause differences in the volumetric conformity during the radiation treatment plan (radiation conformity index), extent of radiated skin, and relationship with the incision site and length. Surgical factors such as soft tissue handling, skin undermining, and retractor placement, not to mention variability in postoperative management such as the nonstandardized use of vacuum-assisted closure, are important variables for wound healing [7, 14]. Ultimately, postoperative blood supply and skin oxygenation appear to be more relevant for wound healing than preoperative assessment using TcO₂.

Where Do We Need To Go?

We know how structural diversity affects the response to radiotherapy, and it may vary based on the dose, fractionation, and quality of radiation [8]. However, endothelial degeneration, capillary occlusion, and ischemia are key pathologic and clinical features of postradiation sequelae [8]. Therefore, the natural question is why oximetry didn’t make a difference, despite the promise seen in the authors’ published pilot study [10] that “proposed using preoperative measurement of TcO₂ at the proposed incision site to classify patients into high-risk and low-risk categories for the development of wound complications after resection” [9].

Although improved detection of diminished skin perfusion seems the most pressing area of inquiry that we should explore, complex postradiation sequelae and surgical complications require broader investigation. Radiation oncology continues to improve, both in terms of treatment efficacy and mitigating or avoiding side effects. The cornerstone of radiobiology for most of the 20th century was the delivery of photon treatments to a relatively wide field at around 2 Gy per fraction, usually 5 days per week for 4 to 7 weeks for curative intent, with shorter and intensified regimens more commonly used for palliation. However, recent advances in technology, imaging, and computing, and the use of charged particles and incorporation of biologic treatments, have considerably expanded the field [5]. The principle of combining biology and technology with hypofractionation and increasingly conformal treatments to target cancer with increased efficacy (and minimal tissue radiation and side effects) is quickly moving from prospective trials to routine care for several types of malignancy. This work in progress includes radiation-enhancing nanoparticles, a new class of agents designed to accumulate in target tissue and amplify radiobiological effects [3].

How Do We Get There?

In my view, the value of any clinical test is directly proportional to the extent the information provided may affect a patient’s management. In this clinical context, an assessment of wound viability in terms of skin perfusion provides more functional and actionable information than transcutaneous oximetry does. Intraoperative use of intravenous indocyanine green (ICG) and near-infrared fluorescence imaging is now well established as a simple and reliable method to visualize tissue vascularity. It is routinely practiced in plastic surgery to assess skin perfusion and flap viability. Indeed, within 3 minutes after the intravenous injection of ICG, ischemic skin can be easily identified by the lack of fluorescence as a discrete and well-demarcated darker area, facilitating excision and giving the surgeon greater confidence in primary closure. Because of its simplicity and immediate applicability, the technique is seeing wider use in musculoskeletal oncology, and its use was recently reported in soft tissue sarcoma surgery [15].

How this approach could be applied and validated in the current context is crucial. As reported in the current study [9], a prospective trial and a systematic review failed to demonstrate convincing evidence of its utility in breast [13] and abdominal [16] reconstructive surgery. Clearly, ensuring that flaps are well vascularized at the time of closure may be more predictive than assessing preoperative transcutaneous oxygenation, and what happens to the skin after surgery is much more relevant for the fate of the wound. Excessive pressure on tissue is a known risk factor for poor perfusion and necrosis [2]; the same principle applies to compression associated with wound closure, which may cause wound dehiscence [1]. Postoperative swelling, hematoma, and even a mildly compressive dressing may critically affect the delicate equilibrium of radiated skin and cause ischemia.

Although a randomized study would clearly be the ideal way to validate the ICG technique, adequately powering a study has proven to be challenging in sarcomas and rare conditions in general; it usually requires multicenter participation and long enrollment periods. In these circumstances, a study with a lower level of evidence may be acceptable, and the prospectively collected data of the treatment arm (ICG) may be compared with those of a control group represented by good-quality historical data, in a 2:1 or 3:1 retrospective match based on a preliminary power analysis. This could be an easier and more practical task while retaining scientific rigor to answer a well-posed question.

Meticulous definition of the research question and outcome measurements are two critical elements of a trial. Equally important are an accurate description of the technique methods and perioperative management, including timing of fluorescence imaging and type of suture and dressing to minimize the risk of significant deviations. As mentioned, tumor size and anatomic location (medial, lateral, or posterior compartment), radiotherapy details (radiation modality, total dose, and fractionation), and patient characteristics should be matched as closely as possible. Postoperative wound surveillance should be performed at specific time intervals to document postoperative baseline and subsequent changes. Surveillance might provide insight into the physiopathology of postradiation skin necrosis that has occurred after the trialists have done what they can to make good decisions about wound closure using standardized approaches. The results of such a study would then help researchers determine whether a higher-quality randomized prospective study would be necessary to answer the clinical question.