Treatment package time < 14 weeks improves recurrence free and disease specific survival in HPV positive OPC with high-risk features.

BACKGROUND: Guidelines recommend treatment package time < 85 days and time from surgery to radiation initiation < 6 weeks in head and neck cancer patients. However, HPV positive primaries treated with TORS and adjuvant radiotherapy traditionally demonstrate favorable outcomes. METHODS: Single center retrospective chart review of patients diagnosed with HPV positive treatment naïve primary squamous cell carcinoma treated with TORS and postoperative radiation therapy with or without Chemotherapy from 2012 to 2022 with data collection from December 2022-April 2023. Kaplan-Meier survival analysis with log-rank testing assessed the impact of time intervalsbetween diagnosis, TORS, radiation initiation and radiation completion on recurrence free and disease specific survival. Univariate Cox proportional hazards regression analysis was performed to identify factors associated with recurrence free and disease specific survival. Subgroup analysis was done with high risk (positive lymph nodes > 5, >1mm extracapsular extension, positive margins) patients who underwent concurrent Chemotherapy. RESULTS: Of 255 patients (225 males [89 %], average age 58 years, 163 [64 %] high-risk, median follow-up 4.3 years), 22 (8.6 %) had recurrence and 14 died due after disease recurrence.Only radiation length of 5-7 weeks prolonged survival in the entire population. In the high-risk cohort, time from TORS to radiation initiation < 6 weeks improvedrecurrence free survival, while total package time < 14 weeks wasassociated with greater recurrence free and disease specific survival.

Lysosomal mitochondrial interaction promotes tumor growth in squamous cell carcinoma of the head and neck.

Tumor growth and proliferation are regulated by numerous mechanisms. Communication between intracellular organelles has recently been shown to regulate cellular proliferation and fitness. The way lysosomes and mitochondria communicate with each other (lysosomal/mitochondrial interaction) is emerging as a major determinant of tumor proliferation and growth. About 30% of squamous carcinomas (including squamous cell carcinoma of the head and neck, SCCHN) overexpress TMEM16A, a calcium-activated chloride channel, which promotes cellular growth and negatively correlates with patient survival. TMEM16A has recently been shown to drive lysosomal biogenesis, but its impact on mitochondrial function is unclear. Here, we show that (1) patients with high TMEM16A SCCHN display increased mitochondrial content specifically complex I; (2) In vitro and in vivo models uniquely depend on mitochondrial complex I activity for growth and survival; (3) ß-catenin/NRF2 signaling is a critical linchpin that drives mitochondrial biogenesis, and (4) mitochondrial complex I and lysosomal function are codependent for proliferation. Taken together, our data demonstrate that LMI drives tumor proliferation and facilitates a functional interaction between lysosomes and mitochondria. Therefore, inhibition of LMI may serve as a therapeutic strategy for patients with SCCHN.

Drainage of anorectal abscesses in the operating room is associated with a decreased risk of abscess recurrence and fistula formation.

BACKGROUND: Timely incision and drainage (I&D) is first line management for anorectal abscesses. We aimed to define current practices in anorectal abscess management and identify factors associated with abscess recurrence and fistula formation. METHODS: Index episodes of anorectal abscesses treated with I&D in 2014-2018 at a multi-hospital healthcare system were included. Association with one-year abscess recurrence or fistula formation was evaluated using Cox proportional hazard regression. Fistulae were captured only among patients without fistulae at the index operation. RESULTS: A total of 458 patients met study criteria. One-year rate of abscess recurrence or fistula formation was 20.3%. When compared to bedside procedures, drainage in the operating room was associated with a reduced risk of either recurrence or fistula formation (aHR 0.20 [95%CI 0.114-0.367]). CONCLUSIONS: Improved exposure and patient comfort in the operating room may allow more complete drainage contributing to decreased rates of abscess recurrence or fistula formation.

Transoral Robotic Surgery for Recurrent Tumors of the Upper Aerodigestive Tract (RECUT): An International Cohort Study.

BACKGROUND: Transoral robotic surgery (TORS) is an emerging minimally invasive surgical treatment for residual, recurrent, and new primary head and neck cancers in previously irradiated fields, with limited evidence for its oncological effectiveness. METHODS: A retrospective observational cohort study of consecutive cases performed in 16 high-volume international centers before August 2018 was conducted (registered at clinicaltrials.gov [NCT04673929] as the RECUT study). Overall survival (OS), disease-free survival, disease-specific survivals (DSS), and local control (LC) were calculated using Kaplan-Meier estimates, with subgroups compared using log-rank tests and Cox proportional hazards modeling for multivariable analysis. Maximally selected rank statistics determined the cut point for closest surgical resection margin based on LC. RESULTS: Data for 278 eligible patients were analyzed, with median follow-up of 38.5 months. Two-year and 5-year outcomes were 69.0% and 62.2% for LC, 71.8% and 49.8% for OS, 47.2% and 35.7% for disease-free survival, and 78.7% and 59.1% for disease-specific survivals. The most discriminating margin cut point was 1.0 mm; the 2-year LC was 80.9% above and 54.2% below or equal to 1.0 mm. Increasing age, current smoking, primary tumor classification, and narrow surgical margins (≤1.0 mm) were statistically significantly associated with lower OS. Hemorrhage with return to theater was seen in 8.1% (n = 22 of 272), and 30-day mortality was 1.8% (n = 5 of 272). At 1 year, 10.8% (n = 21 of 195) used tracheostomies, 33.8% (n = 66 of 195) used gastrostomies, and 66.3% (n = 53 of 80) had maintained or improved normalcy of diet scores. CONCLUSIONS: Data from international centers show TORS to treat head and neck cancers in previously irradiated fields yields favorable outcomes for LC and survival. Where feasible, TORS should be considered the preferred surgical treatment in the salvage setting.

Consensus of free flap complications: Using a nomenclature paradigm in microvascular head and neck reconstruction.

BACKGROUND: We aim to define a set of terms for common free flap complications with evidence-based descriptions. METHODS: Clinical consensus surveys were conducted among a panel of head and neck/reconstructive surgeons (N = 11). A content validity index for relevancy and clarity for each item was computed and adjusted for chance agreement (modified kappa, K). Items with K < 0.74 for relevancy (i.e., ratings of "good" or "fair") were eliminated. RESULTS: Five out of nineteen terms scored K < 0.74. Eliminated terms included "vascular compromise"; "cellulitis"; "surgical site abscess"; "malocclusion"; and "non- or mal-union." Terms that achieved consensus were "total/partial free flap failure"; "free flap takeback"; "arterial thrombosis"; "venous thrombosis"; "revision of microvascular anastomosis"; "fistula"; "wound dehiscence"; "hematoma"; "seroma"; "partial skin graft failure"; "total skin graft failure"; "exposed hardware or bone"; and "hardware failure." CONCLUSION: Standardized reporting would encourage multi-institutional research collaboration, larger scale quality improvement initiatives, the ability to set risk-adjusted benchmarks, and enhance education and communication.

Improving Quality of Life in Hematopoietic Stem Cell Transplantation Survivors Through a Positive Psychology Intervention.

Despite advances in transplantation medicine, psychological distress and quality of life and functional deficits continue to compromise survivorship after hematopoietic stem cell transplantation (HSCT). With increasing numbers of HSCT survivors, supportive oncology interventions that target health-related outcomes in HSCT survivorship are needed. Here we aimed to test the feasibility and acceptability of a group format phone-delivered positive psychology (PP) intervention in HSCT survivors. This is a one-arm pilot study design that adapted and tested an individual PP intervention used in cardiac disease to a phone-delivered group-based program for HSCT survivors who were .4 to 39 years post-transplantation. All participants received an 8-session weekly PP intervention. We assessed feasibility by the enrollment and intervention completion rates. We examined acceptability on a 10-point Likert scale of ease and utility. Unstructured qualitative interviews were used to obtain participant feedback on the intervention for future application in a larger trial. Self-reported assessments on psychological, functional, and quality of life outcomes were administered at baseline and at follow-up (the end of the intervention). Of 64 eligible participants, 29 (45%) enrolled in the study. For the main aim of intervention feasibility and acceptability, participants completed 96% of all PP sessions and rated the ease (7.6 ± 1.7) and utility (8.1 ± 1.1) of sessions highly. Of the self-reported assessments obtained, the PP intervention resulted in improvements in the resilience scale (mean difference, 2.4 ± 5.4; P = .03). From unstructured qualitative interviews, participants reported the PP exercises and intervention helped them to focus on positive emotions and the group format fostered a sense of community and social support. An 8-week phone-delivered group format PP intervention is feasible and acceptable in HSCT survivors. The piloted intervention could be tested with minor modifications in a randomized study to definitively examine the impact of the group format PP intervention on health-related outcomes.

Carfilzomib for Treatment of Refractory Chronic Graft-versus-Host Disease: A Chronic GVHD Consortium Pilot Phase II Trial.

Previously reported experimental and clinical data suggest that proteasome inhibition may have immunomodulatory activity relevant to graft-versus-host disease (GVHD). To explore the safety and activity of carfilzomib in advanced chronic GVHD, we conducted a multicenter pilot phase II trial through the Chronic GVHD Consortium. Carfilzomib was administered at 20 mg/m2 on day 1, then 36 mg/m2 on days 8 and 15 of a 28-day treatment cycle (cycle 1), and then 36 mg/m2 on days 1, 8, and 15 of a 28-day treatment cycle (cycles 2 to 6). The primary endpoint was 6-month treatment failure, a composite endpoint including death, relapse, and requirement for an additional line of systemic immunosuppressive therapy. A total of 20 subjects were enrolled at 4 institutions. The median time from chronic GVHD onset to enrollment was 1.5 years (interquartile range, 0.5 to 3.7 years). Chronic GVHD was National Institutes of Health category moderate (30%) or severe (70%), predominantly classic (90% versus overlap 10%), and involved multiple diverse organ sites. The number of previous lines of systemic therapy for chronic GVHD was ≤2 in 6 patients (30%) and ≥3 in the other 14 (70%). Doses were held primarily for infection (50% of total held doses); only 3 patients (15%) completed all planned doses of the 6 cycles of carfilzomib. Serious adverse effects occurred in 40% of the patients, and 7 patients died, between .3 and 9 months after the last carfilzomib dose, but no deaths were attributed to carfilzomib. The 6-month treatment failure rate was not significantly improved versus the historical benchmark rate (40% versus 44%; P = .36). Overall survival was 80% at 6 months and 65% at 12 months. Failure-free survival at 12 months was 32%. These pilot phase II data suggest that carfilzomib therapy in this advanced chronic GVHD population did not improve over the expected 6-month treatment failure rates achieved under conventional practices and is not recommended for further study for this indication.

Rates and Risk Factors for Post-Traumatic Stress Disorder Symptomatology among Adult Hematopoietic Cell Transplant Recipients and Their Informal Caregivers.

Hematopoietic cell transplant (HCT) can cause significant distress in patients and their informal caregivers. Despite advances in reduced-intensity conditioning and supportive care, few recent studies have reported rates of clinically significant post-traumatic stress disorder (PTSD) symptomatology. Goals of the current study were to examine rates of PTSD and distress in patients and caregivers and to identify sociodemographic and clinical risk factors for PTSD. As part of an annual survivorship survey, 2157 HCT recipients and their caregivers were mailed self-report measures of PTSD and distress. Patients also completed self-report measures of sociodemographic information (eg, age, sex, employment status). Clinical variables (eg, time since transplant, transplant type) were captured in the transplant database. A total of 691 recipients (56% age 60 or above at the time of survey, 47% women, median 10.1 years post-HCT) and 333 caregivers provided PTSD data and were included in the current analyses. More caregivers reported PTSD (6.6%) than patients (3.3%; P = .02). Patients or caregivers who had PTSD reported significantly higher distress related to uncertainty, family strain, medical demands, finances, identity, and health burden (P < .0001) compared with those without PTSD. Patient but not caregiver PTSD was associated with more recent transplant (P = .01 and P = .16, respectively). Rates of PTSD are relatively low in long-term survivors of HCT and their caregivers. Nevertheless, results are consistent with other studies of cancer caregiving suggesting that caregivers often experience greater distress than patients. Timely referral to psychosocial services should be offered to both HCT recipients and caregivers reporting symptoms of PTSD.