Post-treatment PET/CT for p16-positive oropharynx cancer treated with definitive proton therapy.

Objectives: Given emerging data suggesting that uncertainty in the relative biologic effectiveness at the distal end of the Bragg peak results in increased mucosal injury in patients with oropharynx cancer receiving adjuvant proton therapy, we evaluated the results of post-treatment positron emission tomography-computed tomography (PET/CT) in patients with p16-positive oropharynx cancer (p16+OPC) treated with definitive intensity-modulated proton therapy (IMPT). Material and Methods: A retrospective cohort study of patients with p16+OPC treated with definitive IMPT between 2016 and 2022 was performed at a single institution. Patients with PET/CT scans within 6 months following completion of IMPT were included in the study. Positive post-treatment scans were defined by a maximum standard uptake values (SUVmax) >4.0 or a <65% reduction in SUVmax in either the primary tumor or lymph node. The Fisher's exact test was used to evaluate factors associated with positive post-treatment PET/ CT values. Results: Sixty-two patients were included for analysis. Median follow-up was 21 months (range: 3-71 months) with a median time to post-treatment PET/CT of 3 months (range: 2-6 months). Median post-treatment SUVmax of the primary disease and nodal disease was 0 (mean: 0.8, range: 0-7.7) and 0 (mean: 0.7, range: 0-9.5), respectively. Median post-treatment percent reduction in SUVmax for the primary site and lymph node was 100% (mean: 94%, range: 31.3-100%) and 100% (mean: 89%, range: 23-100%), respectively. Eleven patients had a positive post-treatment PET/CT with one biopsy-proven recurrence. Negative and positive predictive values (NPV and PPV) were 98% and 9.1%, respectively. There were no factors associated with positive post-treatment PET/CT. Conclusion: Similar to patients treated with photon-based radiation therapy, post-treatment PET/CT has a high NPV for patients with p16+OPC treated with definitive proton therapy and should be used to guide patient management. Additional patients and more events are needed to confirm the PPV of a post-treatment PET/CT in this favorable patient cohort.

Contralateral Lower Extremity Ischemia on Femoral Veno-Arterial Extracorporeal Membrane Oxygenation.

Ipsilateral lower extremity ischemia is a common and morbid complication during veno-arterial extracorporeal membrane oxygenation (VA-ECMO). The cannula can impede ipsilateral distal arterial flow leading to critical limb ischemia. Cannula size, placement, and utilization of distal perfusion catheters are strategies that have been used to prevent this complication. We report the novel case of a 19-year-old female on VA-ECMO complicated by contralateral lower extremity ischemia. Diagnosis was made by computed tomography, and with repositioning of the femoral arterial cannula, she had a complete resolution of symptoms.

Gross tumor volume margin and local control in p16-positive oropharynx cancer patients treated with intensity modulated proton therapy.

BACKGROUND: To determine if the extent of high-dose gross tumor volume (GTV) to clinical target volume (CTV) expansion is associated with local control in patients with p16-positive oropharynx cancer (p16+ OPC) treated with definitive intensity modulated proton therapy (IMPT). METHODS: We performed a retrospective analysis of patients with p16+ OPC treated with IMPT at a single institution between 2016 and 2021. Patients with a pre-treatment PET-CT and restaging PET-CT within 4 months following completion of IMPT were analyzed. RESULTS: Sixty patients were included for analysis with a median follow-up of 17 months. The median GTV to CTV expansion was 5 mm (IQR: 2 mm). Thirty-three percent of patients (20 of 60) did not have a GTV to CTV expansion. There was one local failure within the expansion group (3%). CONCLUSION: Excellent local control was achieved using IMPT for p16+ OPC independent of GTV expansion. IMPT with minimal target expansions represent a potential harm-minimization technique for p16-positive oropharynx cancer.

Bedside angiography of distal perfusion catheter for veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: The aim of this study was to evaluate the ipsilateral lower extremity (ILE) outcomes of patients who underwent bedside angiography via the distal perfusion catheter while on femoral veno-arterial extracorporeal membrane oxygenation (VA ECMO). METHODS: This is a retrospective analysis of all patients placed on VA ECMO at a single center from January 2017 to December 2019 who underwent bedside angiography via the distal perfusion catheter. RESULTS: Twenty-four patients underwent bedside angiography via the distal perfusion catheter after being placed on VA ECMO. A vasodilator was directly administered in three patients for suspected spasm. One patient had distal thrombus and underwent thrombectomy and fasciotomy. One patient had a dislodged catheter and underwent thrombectomy, fasciotomy, and replacement of the catheter. One patient had severe ILE ischemia, however was not intervened upon due to critical acuity. Finally, one patient had inadvertent placement in the saphenous vein and had a new catheter placed in the SFA. No patients underwent amputation. Ultimately, 21 patients (87.5%) had no ILE compromise at the end their ECMO course. Survival to decannulation was 66.7% (n = 16). CONCLUSIONS: Bedside angiography of the distal perfusion catheter is feasible and can be a useful adjunct in informing the need for further intervention to the ILE. CLASSIFICATIONS: extracorporeal membrane oxygenation, ischemia.

Mesothelin Enhances Tumor Vascularity in Newly Forming Pancreatic Peritoneal Metastases.

Over 90% of pancreatic ductal adenocarcinomas (PDAC) express mesothelin (MSLN). Overexpression or knockdown of MSLN has been implicated in PDAC aggressiveness. This activity has been ascribed to MSLN-induced activation of MAPK or NF-κB signaling pathways and to interaction of MSLN with its only known binding partner, MUC16. Here, we used CRISPR/Cas9 gene editing to delete MSLN from PDAC, then restored expression of wild-type (WT) or Y318A mutant MSLN by viral transduction. We found that MSLN KO cells grew in culture and as subcutaneous tumors in mouse xenografts at the same rate as WT cells but formed intraperitoneal metastases poorly. Complementation with WT MSLN restored intraperitoneal growth, whereas complementation with Y318A mutant MSLN, which does not bind MUC16, was ineffective at enhancing growth in both MUC16(+) and MUC16(-) models. Restoration of WT MSLN did enhance growth but did not affect cell-to-cell binding, cell viability in suspension or signaling pathways previously identified as contributing to the protumorigenic effect of MSLN. RNA deep sequencing of tumor cells identified no changes in transcriptional profile that could explain the observed phenotype. Furthermore, no histologic changes in tumor cell proliferation or morphology were observed in mature tumors. Examination of nascent MSLN KO tumors revealed decreased microvascular density as intraperitoneal tumors were forming, followed by decreased proliferation, which resolved by 2 weeks postimplantation. These data support a model whereby MSLN expression by tumor cells contributes to metastatic colonization. IMPLICATIONS: MSLN confers a growth advantage to tumor cells during colonization of peritoneal metastasis. Therapeutic blockade of MSLN might limit peritoneal spread.