The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.     

Long term cutaneous complications related to bone conduction hearing implants. A retrospective study (2004–2018)

ObjectiveThe aim of this study was to establish the frequency of cutaneous complications due to surgically implanted bone conduction hearing aids in recipients treated at a tertiary otolaryngology center. Additionally, based on the literature review, we propose a scale to standardize the report of cutaneous reactions related to transcutaneous systems to objectify future studies.MethodsA retrospective chart review was conducted for patients who were implanted with bone conduction hearing systems between 2004 and 2018. Patients with minimum follow up of 6 months were included. Patient demographics, surgical characteristics and clinical course was analyzed by number and skin reactions. Transcutaneous and percutaneous systems were analyzed separately. The study was approved by the local IRB.ResultsA total of 104 devices were implanted on 88 patients with an average follow up of 4.04 (range of 0.5 - 10 years). Out of the total of patients, 49 (55.7%) developed at least one episode of inflammatory/infectious skin reaction at surgical incision site. A total of 148 episodes of local infections during the entire follow-up period were registered, mostly mild in severity with no triggering factors identified. The majority of the initial episodes of infection occurred within the first 3 years of follow-up. Out of the total of patients, 47 (53.4%) reported pain at the surgical site at some point throughout follow-up, not associated with clinically evident infection.ConclusionThe incidence of skin complications in our series seemed higher compared to previous reports. Minor complications were the most common and responded well to topical treatment. No triggering factors were identified as the cause of the infections, nor to explain the frequency or the severity of such an adverse reaction. Isolated pain was present in the majority of patients with conductive hearing devices, even without signs of active infection. Due to its high incidence it should be assessed in all patients that receive an implant.Based on a search of the literature, a scale to standardize cutaneous complications of transcutaneous implants was undertaken, but further studies are needed to validate such a scale.