Definitive treatment for primary urethral cancer: A single institution's experience with organ-preserving brachytherapy.

BACKGROUND: Radical urethectomy ± cystectomy has long represented the standard of care for rare primary urethral cancer (PUC). With our analysis, we want to demonstrate the efficacy and safety of brachytherapy (BT) of urethra for organ preservation. MATERIALS AND METHODS: We analyzed treatment procedures and results of 3 patients with PUC, which have been treated in our department between 2011 and 2020 with brachytherapy. One male patient underwent brachytherapy with chemoradiotherapy after transurethral resection (TUR). Brachytherapy has been performed as high-dose-rate (HDR) boost with a cumulative dose of 8 Gy (9.3 Gy EQD2-α/ß = 10 Gy). The 2 further female patients have been treated with sole pulsed-dose-rate (PDR) brachytherapy with a total dose of 49.9 Gy (50.3 Gy EQD2-α/ß = 10 Gy) and 62.2 Gy (64.6 Gy EQD2-α/ß = 10 Gy). RESULTS: Median follow-up was 103 months (41-153). No local recurrence occurred and all patients are still alive. For the male patient we documented Grade 3 cystitis. As late side effects the pre-existing Grade 2 incontinence worsened to Grade 3. Among female patients one developed Grade 3 vaginal synechiae. There was no Grade ≥4 toxicity. CONCLUSION: Brachytherapy in PUC is a feasible and promising option with high local control rate and tolerable toxicity. It provides a good alternative to surgery for organ preservation in selected patients.

Upfront Neck Dissection in Organ Preservation Protocol in Head-Neck SCC : Can it be a Game Changer?

The major prognostic factor in head-neck squamous cell carcinoma is the status of lymph nodes. Though there are studies addressing the role of neck dissection in organ preservation protocol, a lacuna still exists as far as the question of upfront neck dissection arises. Despite the potential benefits of upfront neck dissection; the benefits have not been well researched and thus its place in management of head-neck cancers undergoing organ preservation protocol is still questionable. We conducted an observational study in 22 patients with T1 - 2N2 - 3a biopsy proven squamous cell carcinoma of hypopharynx, oropharynx and laryngopharynx which were eligible for organ preservation protocol for their primary site. The primary outcome was to calculate their overall survival rate at 5 years. Overall 5 year survival rate was 68.12%, 5-year Disease free survival rate was 77.2%. The time to start for the primary site, after neck dissection however had a significant effect on overall survival. Those who had a delay of 21 days or less had 80.1% survival at 5 years compared to those who started at 30 days (61.3%) and drastically reduced in those who started at 39 days (20.4%). Log-rank test for the effect of nodal status showed a significant difference in terms of 5 year survival between the groups(p = .027). The 5 year survival rates for N2A, N3A and N2B nodal status were 88.8%, 50% ,and 54.5% ,respectively. We strongly favour upfront neck dissections in a subset of head-neck squamous cell carcinoma cases with T1 - 2N2 - 3a eligible for organ preservation regimen.

Outcomes of Distal Rectal Cancer Patients Who Did Not Qualify for Watch-and-Wait: Comparison of Intersphincteric Resection Versus Abdominoperineal Resection.

INTRODUCTION: Total mesorectal excision (TME) with intersphincteric resection and handsewn coloanal anastomosis (ISR-CAA) has been shown to be oncologically safe in patients with distal rectal cancer treated with preoperative chemoradiation. The introduction of the watch-and-wait (WW) strategy for rectal cancer patients with a clinical complete response to neoadjuvant therapy is changing the profile of patients undergoing TME surgery immediately following neoadjuvant treatment. The outcomes of ISR-CAA for patients with locally advanced rectal cancers not qualifying for WW have not been investigated. METHODS: We conducted a retrospective analysis comparing the outcomes of ISR-CAA and abdominoperineal resection (APR) in patients with distal rectal cancer treated with neoadjuvant therapy and not qualifying for WW, at a comprehensive cancer center with an established WW program. The primary outcome was local recurrence-free survival. RESULTS: Sixty-seven patients had ISR-CAA and 79 had APR. Median follow-up was 61.1 months. The two groups were similar in sex, tumor stage, grade, and distance from the anal verge, but patients in the APR group were older on average. An R0 resection was achieved in 94% of ISR-CAA patients and 91% of APR patients. Patients in the ISR-CAA group had a lower 5-year rate of local recurrence-free survival (79% vs. 93%; p = 0.038) compared with the APR group; however, 5-year disease-free survival did not differ significantly between groups (67% for ISR-CAA and 64% for APR; p = 0.19). CONCLUSIONS: The local recurrence rate after ISR-CAA may be higher than after APR for patients without a clinical complete response to neoadjuvant therapy requiring TME surgery.

The combination of post-mortem sevoflurane ventilation and in situ topical cooling provides improved 6h lung preservation in an uncontrolled DCD porcine model.

BACKGROUND: Recent clinical series on donation after uncontrolled cardiovascular death (uDCD) reported successful transplantation of lungs preserved by pulmonary inflation up to 3h post-mortem. This study aims to investigate the additive effects of in situ lowering of intrathoracic temperature and sevoflurane preconditioning on lung grafts in a porcine uDCD model. METHODS: After uDCD induction, donor pigs were allocated to one of the following groups: Control - static lung inflation only (SLI); TC - SLI + continuous intrapleural topical cooling (TC); or TC+Sevo - SLI + TC + sevoflurane. Lungs were retrieved 6h post-asystole and evaluated via ex vivo lung perfusion (EVLP) for 6h. A left single lung transplant was performed using lungs from the best performing group, followed by 4h of graft evaluation. RESULTS: Animals that received topical cooling achieved intrathoracic temperature < 15°C within 1 hour after chest filling of coolant. Only lungs from donors that received TC and TC+Sevo completed the planned post-preservation 6h EVLP assessment. Despite similar early performance of the two groups on EVLP, the TC+Sevo group was superior - associated with overall lower airway pressures, higher pulmonary compliances, less edema development, and less release of inflammatory cytokines. Transplantation was performed using lungs from the TC+Sevo group, and excellent graft function was observed post-reperfusion. CONCLUSION: Preservation of uDCD lungs with a combination of static lung inflation, topical cooling and sevoflurane treatment maintains good pulmonary function up to 6h post-mortem with excellent early post-lung transplant function. These interventions may significantly expand the clinical utilization of uDCD donor lungs.

Ice-cold storage or controlled hypothermia to preserve marginal grafts in high-risk heart transplantation.

BACKGROUND: To evaluate the effectiveness of the Paragonix SherpaPak cardiac transport system (PSP) compared to the standard ice-cold storage (ICS) in extended-criteria donor grafts implanted in high-risk recipients. METHODS: Data of all HTx at the University Centers of Udine and Bologna, between January 2020 and December 2023, employing extended-criteria donors in high-risk HTx conditions were retrospectively analyzed. Patient outcomes and complications after HTx were assessed. Endomyocardial biopsies were performed in donor hearts immediately after retrieval (T0), before implantation (T1) and at reperfusion (T2) to evaluate signs of myocardial damage. RESULTS: Overall, 90 patients who had heart transplantation (HTx) with a donor graft preserved with either ICS (n = 60) or PSP (n = 30) were included in the study. The 30-day mortality was 3% in both groups (p = 0.99), and 1-year survival 90% and 88% (p = 0.89) for recipients transplanted with PSP and ICS preserved grafts. Rates of moderate-to-severe graft dysfunction and bradi-arrhythmias for PSP and ICS groups were 7% versus 20% (p = 0.08), and 3% versus 15% (p = 0.09). Histologically, severe degrees of cellular and endothelial damage were absent in all PSP grafts while severe degree of contraction bands were higher in ICS hearts at T2. CONCLUSIONS: In high-risk donor-recipient matching, donor heart preservation with PSP seems to show a tendency toward better graft protection.

Tumor response rates based on initial TNM stage and tumor size in locally advanced rectal cancer: a useful tool for shared decision-making.

BACKGROUND: It is accepted that tumor stage and size can influence response to neoadjuvant therapy in locally advanced rectal cancer (LARC). Studies on organ preservation to date have included a wide variety of size and TNM stage tumors. The aim of this study was to report tumor response based on each relevant TNM stage and tumor size. METHODS: Patients treated with LARC from 2014 to 2021 with cT2-3NxM0 tumors who received neoadjuvant chemoradiotherapy with or without induction chemotherapy were included. Tumors were staged and tumor size calculated on pelvic MRI at the time of diagnosis (cTNM). Tumor size was based on the largest dimension taken on the longest axis of each tumor. Clinical response was defined on the basis of post-treatment pelvic MRI and pathological response following surgery, when performed. Statistical analysis was performed using IBM SPSS Statistics™, version 20. Data from 432 patients were analyzed as follows: cT2N0 (n = 51), cT2N+ (n = 36), cT3N0 (n = 76), cT3N+ (n = 270). RESULTS: The rate of complete or near-complete response (cCR or nCR) varied from 77% in cT2N0 ≤ 3 cm to 20% in cT3N+ > 4 cm. Organ preservation without recurrence at 2 years was achieved in 86% of patients with cT2N0, 50% in cT2N+, 39% in cT3N0, and 12% in cT3N+. CONCLUSION: There is significant variation in tumor response according to tumor stage and size. Tumor response appears inversely proportional to increasing TNM stage and tumor size. This data can support both refinement of selective patient recruitment to organ preservation programs and shared decision-making.

Retrospective Analysis of Laryngeal Cancer Patients in a Tertiary Referral Center.

Objective: In this study, we aimed to evaluate the effects of demographic data and comorbid diseases on the prognosis and treatment diagnosed with laryngeal squamous cell cancer (LSCC). Methods: Medical records of LSCC patients treated and followed up in a single referral center between 2008 and 2019 were retrospectively reviewed. In addition to the demographic data, the results of overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional-free survival (LRFS), and factors affecting recurrence were analyzed. Results: We included 573 patients with a mean age of 60.1±9.8 years. Of the 573 patients, 94.2% (540) were men, 93.7% (537) were smokers, 40.1% had at least one comorbid disease, and 69.8% (400) presented with glottic LSCC. The five-year OS, DSS, DFS, and LRFS rates for all cases were 65.7%, 79.9%, 67%, and 74.7%, respectively. In early-stage LSCC treatment, the rates of OS (p=0.008), DFS (p=0.024) and LRFS (p=0.01) were statistically significantly higher in the endolaryngeal laser surgery (ELS) group compared with the radiotherapy (RT) group. In advanced-stage LSCC treatment, total laryngectomy had statistically significantly higher five-year DFS (p=0.003) and LRFS (p=0.002) rates compared to chemoradiotherapy. Conclusion: Our study showed that ELS provided higher rates of OS, DFS, and LRFS compared to RT in the treatment of early-stage LSCC. Recurrence was significantly higher in supraglottic tumors, advanced-stage tumors, and in patients with clinical N positivity.

The European Larynx Organ Preservation Study [MK-3475-C44].

The European Larynx Organ Preservation Study (ELOS; NCT06137378) is a prospective, randomized, open-label, two-armed parallel group controlled, phase II multicenter larynx organ preservation (LOP) trial in locoregionally advanced (LA) stage III, IVA/B head and neck squamous cell carcinoma of the larynx or hypopharynx (LHSCC) amenable for total laryngectomy (TL) with PD-L1 expression within tumor tissue biopsy, calculated as CPS ≥ 1. Induction chemotherapy (IC) with docetaxel and cisplatin (TP) followed by radiation will be compared to TP plus PD-1 inhibition by pembrolizumab (MK-3475; 200 mg i.v. starting day 1 q3w for 17 cycles). After a short induction early response evaluation (ERE) 21 ± 3 days after the first cycle of IC (IC-1), responders achieving endoscopic estimated tumor surface shrinkage (ETSS) ≥30% will get an additional two cycles of IC followed by intensity-modulated radiotherapy 70-72 Gy (EQD2/α/ß = 10) aiming at LOP. Nonresponders (ETSS < 30% or progressing disease) will receive TL and bilateral neck dissection followed by postoperative radiation or chemoradiation as recommended by the clinic's multidisciplinary tumor board. Pembrolizumab treatment will be continued in the intervention arm regardless of ETSS status after IC-1 in both responders and laryngectomized nonresponders, independent of subsequent decisions on adjuvant therapy after TL. Clinical Trial Registration: clinicaltrials.gov, identifier NCT06137378.

Antegrade persufflation of porcine kidneys improves renal function after warm ischemia.

Introduction: Transplantation of kidneys from expanded criteria donors (ECD), including after circulatory death (DCD), is associated with a higher risk of adverse events compared to kidneys from standard criteria donors. In previous studies, improvements in renal transplant outcomes have been seen when kidneys were perfused with gaseous oxygen during preservation (persufflation, PSF). In the present study, we assessed ex-vivo renal function from a Diffusion Contrast Enhanced (DCE)-MRI estimation of glomerular filtration rate (eGFR); and metabolic sufficiency from whole-organ oxygen consumption (WOOCR) and lactate production rates. Methods: Using a porcine model of DCD, we assigned one kidney to antegrade PSF, and the contralateral kidney to static cold storage (SCS), both maintained for 24 h at 4°C. Post-preservation organ quality assessments, including eGFR, WOOCR and lactate production, were measured under cold perfusion conditions, and biopsies were subsequently taken for histopathological analysis. Results: A significantly higher eGFR (36.6 ± 12.1 vs. 11.8 ± 4.3 ml/min, p < 0.05), WOOCR (182 ± 33 vs. 132 ± 21 nmol/min*g, p < 0.05), and lower rates of lactate production were observed in persufflated kidneys. No overt morphological differences were observed between the two preservation methods. Conclusion: These data suggest that antegrade PSF is more effective in preserving renal function than conventional SCS. Further studies in large animal models of transplantation are required to investigate whether integration with PSF of WOOCR, eGFR or lactate production measurements before transplantation are predictive of post-transplantation renal function and clinical outcomes.

Organ preservation after neoadjuvant long-course chemoradiotherapy versus short-course radiotherapy.

BACKGROUND: Potential differences in organ preservation between total neoadjuvant therapy (TNT) regimens integrating long-course chemoradiotherapy (LCCRT) and short-course radiotherapy (SCRT) in rectal cancer remain undefined. PATIENTS AND METHODS: This natural experiment arose from a policy change in response to the COVID-19 pandemic during which our institution switched from uniformly treating patients with LCCRT to mandating that all patients be treated with SCRT. Our study includes 323 locally advanced rectal adenocarcinoma patients treated with LCCRT-based or SCRT-based TNT from January 2018 to January 2021. Patients who achieved clinical complete response were offered organ preservation with watch-and-wait (WW) management. The primary outcome was 2-year organ preservation. Additional outcomes included local regrowth, distant recurrence, disease-free survival (DFS), and overall survival (OS). RESULTS: Patient and tumor characteristics were similar between LCCRT (n = 247) and SCRT (n = 76) cohorts. Median follow-up was 31 months. Similar clinical complete response rates were observed following LCCRT and SCRT (44.5% versus 43.4%). Two-year organ preservation was 40% [95% confidence interval (CI) 34% to 46%] and 31% (95% CI 22% to 44%) among all patients treated with LCCRT and SCRT, respectively. In patients managed with WW, LCCRT resulted in higher 2-year organ preservation (89% LCCRT, 95% CI 83% to 95% versus 70% SCRT, 95% CI 55% to 90%; P = 0.005) and lower 2-year local regrowth (19% LCCRT, 95% CI 11% to 26% versus 36% SCRT, 95% CI 16% to 52%; P = 0.072) compared with SCRT. The 2-year distant recurrence (10% versus 6%), DFS (90% versus 90%), and OS (99% versus 100%) were similar between WW patients treated with LCCRT and SCRT, respectively. CONCLUSIONS: While WW eligibility was similar between cohorts, WW patients treated with LCCRT had higher 2-year organ preservation and lower local regrowth than those treated with SCRT, yet similar DFS and OS. These data support induction LCCRT followed by consolidation chemotherapy as the preferred TNT regimen for patients with locally advanced rectal cancer pursuing organ preservation.

Contact X-ray Brachytherapy as a sole treatment in selected patients with early rectal cancer - Multi-centre study.

Background and purpose: Radical surgery is the standard of care for early rectal cancer. However, alternative organ-preserving approaches are attractive, especially in frail or elderly patients as these avoid surgical complications. We have assessed the efficacy of sole Contact X-ray Brachytherapy (CXB) treatment in stage-1 rectal cancer patients who were unsuitable for or declined surgery. Materials and methods: This retrospective multi-centre study (2009-2021) evaluated 76 patients with T1/2-N0-M0 rectal adenocarcinomas who were treated with CXB alone. Outcomes were assessed for the entire cohort and sub-groups based on the T-stage and the criteria for receiving CXB alone; Group A: patients who were fit enough for surgery but declined, Group B: patients who were high-risk for surgery and Group C: patients who had received prior pelvic radiation for a different cancer. Results: With a median follow-up of 26(IQR:12-49) months, initial clinical Complete Response (cCR) was 82(70-93)% with rates of local regrowth 18(8-29)%, 3-year actuarial local control (LC) 84(75-95)%, distant relapse 3 %, and no nodal relapse. 5-year disease-free survival (DFS) and overall survival (OS) were 66(48-78)% and 58(44-75)%. Lower OS was observed in Groups B [HR:2.54(95 %CI:1.17, 5.59), p = 0.02] and C [HR:2.75(95 %CI:1.15, 6.58), p = 0.03]. Previous pelvic radiation predicted lower cCR and OS. The main toxicity was G1-2 rectal bleeding (26 %) and symptoms of impaired anal sphincter function were not reported in any patients. Conclusion: CXB treatment alone achieved a high cCR rate with satisfactory LC and DFS. Inferior oncological outcomes were observed in patients who had received prior pelvic radiotherapy. CXB alone, with its favourable toxicity profile and avoidance of general anaesthesia and surgery risks, therefore, can be considered for patients who are unsuitable for or refuse surgery.

Paediatric donor lung preservation using Paragonix BAROguard.

Paediatric lung transplantation is a lifesaving option in selected patients with end-stage lung disease. Favourable long-term outcomes are limited by impaired mucus clearance, increased risk of infection resulting from immunosuppression, and chronic lung allograft dysfunction. Organ preservation techniques play an important role in the quality of donated organs. Barotrauma to donated lungs may arise from a combination of excessive recruitment manoeuvres and altitude change during air transportation. The Paragonix BAROguard Donor Lung Preservation System is an FDA-approved advanced organ recovery system that maintains continuous airway pressure of 15 cm of water during transportation of the donated lung(s) to the recipient. The Paragonix LUNGguard monitors temperature during transportation of donor lung(s), while the new BAROguard monitors both temperature and pressure during transportation of donor lung(s). In this publication, we present technical aspects of advanced preservation of paediatric donor lungs using the Paragonix BAROguard Donor Lung Preservation System.

Production of physiological amounts of hemostatic proteins by human donor livers during ex situ long-term normothermic machine perfusion for up to 7 days.

BACKGROUND: Normothermic machine perfusion (NMP) is used for preservation and assessment of human donor livers prior to transplantation. During NMP, the liver is metabolically active, which allows detailed studies on the physiology of human livers. OBJECTIVES: To study the production of hemostatic proteins in human donor livers during NMP for up to 7 days. METHODS: In this observational study, 9 livers underwent NMP for up to 7 days with a heparinized perfusate based on red blood cells and colloids using a modified Liver Assist device (XVIVO). Perfusate samples were collected before NMP and daily thereafter for measurement of antigen and activity levels of a comprehensive panel of hemostatic proteins after heparin neutralization. RESULTS: Within 1 day, perfusate samples displayed the potential for coagulation activation as evidenced by international normalized ratio and activated partial thromboplastin assays. This was accompanied by detection of substantial quantities of functionally active coagulation proteins and inhibitors, although the specific activity of many proteins was decreased, compared with that in normal plasma. Perfusate levels of hemostatic proteins increased in the first days, reaching a stable level after 3 to 4 days of perfusion. CONCLUSION: During long-term NMP of human livers, functionally active hemostatic proteins are released into the perfusate in substantial quantities, but some proteins appear to have decreased functional properties compared with proteins in normal human plasma. We propose that NMP may be used as a platform to test efficacy of drugs that stimulate or inhibit the production of coagulation factors or to test liver-mediated clearance of prohemostatic protein therapeutics.

The Rise of Patients Declining Rectal Cancer Surgery in the Era of Total Neoadjuvant Therapy.

BACKGROUND: The treatment landscape for rectal cancer is rapidly evolving, particularly with the increasing use of neoadjuvant therapies. Still, up to 50% of patients with stage II-III disease require surgical resection post-neoadjuvant therapy to achieve the best oncologic outcomes. Many patients, however, hope to avoid surgery. This study aimed to assess trends and factors associated with declining recommended oncologic resection after systemic therapy nationally and in our institution. PATIENTS AND METHODS: This is a retrospective analysis using the National Cancer Database from 2009 to 2021 and an institutional cohort at an academic center between 2009 and 2022 including adults with stage I-III rectal adenocarcinoma who underwent neoadjuvant therapy and were suitable for surgery. RESULTS: Of 96,997 patients nationally, the rate of declining surgery increased from 2.3% in 2009 to 6.3% in 2021, a trend mirrored in our institutional cohort of 365 patients (0% in 2009/2010 to approximately 6-12% in 2021/2022). Locally, patients who declined surgery had higher rates of tobacco use, temporary loss to follow-up during therapy, and a more robust, albeit incomplete, tumor response to neoadjuvant therapy compared with controls who underwent surgery. Despite a stoma being the most cited reason for declining surgery, 30.4% of patients who declined oncologic resection died with a stoma. CONCLUSIONS: Our findings underscore a notable trend of patients declining oncologic resections following neoadjuvant therapy for rectal cancer. By shedding light on the outcomes of patients who opt against surgery, we address a critical gap in the literature essential for informing patients about potential risks.

Survival, function, and immune profiling after beating heart transplantation.

OBJECTIVE: Ex vivo normothermic perfusion of cardiac allografts has expanded the donor pool for heart transplant. Using a beating heart implantation method avoids the second cardioplegic arrest and subsequent ischemia-reperfusion injury typically associated with ex vivo heart perfusion. We sought to describe our institutional experience with beating heart transplantation. METHODS: This was a single-institution retrospective study of adult patients who underwent heart transplantation using ex vivo heart perfusion (EVHP) and a beating heart implantation technique between October 2022 and March 2024. Primary outcomes of interest included survival, initiation of mechanical circulatory support, and rejection. A subanalysis of our institutional series of nonbeating deceased after circulatory death (DCD) heart transplantations was performed as well. RESULTS: Twenty-four patients underwent isolated heart transplantation with the use of ex vivo heart perfusion and beating heart implantation between October 2022 and March 2024; 21 (87.5%) received hearts from DCD donors, and 3 (12.5%) received hearts from deceased after brain death (DBD) donors. The median duration of follow-up was 192 days (interquartile range [IQR], 124-253.5 days), and 23 out of 24 patients (95.8%) were alive at last follow-up. No patients required initiation of mechanical circulatory support. The majority of patients had pathologic grade 0 rejection at the time of biopsy (n = 16; 66.7%), and the median cell-free DNA percent was 0.04% (IQR, 0.04%-0.09%). The rate of mechanical circulatory support initiation in the 22-patient nonbeating DCD heart transplant cohort was significantly higher, at 36.4% (P < .005). CONCLUSIONS: A beating heart implantation technique can be used for transplantation of DCD and DBD hearts on EVHP and is associated with excellent survival and low levels of rejection.

Orthostatic Ex-Vivo Lung Perfusion (EVLP): A Proof of Concept.

The key goal in lung donation remains the improvement of graft preservation with the ultimate objective of increasing the number and quality of lung transplants (LTx). Therefore, in recent years the field of graft preservation focused on improving outcomes related to solid organ regeneration and restoration. In this contest Ex-Vivo Lung Perfusion (EVLP) plays a crucial role with the purpose to increase the donor pool availability transforming marginal and/or declined donor lungs suitable for transplantation. Aim of this proof of concept is to test the safety, suitability and feasibility of a new tilting dome for EVLP designed considering the dorsal lung areas as the "Achilles' heel" of the EVLP due to a more fluid accumulation than in the supine standard position.

Elective vs. emergency tracheotomy complications in advanced hypopharyngeal cancer.

Squamous cell carcinoma of the hypopharyngeal region is a rare, aggressive disease with a poor prognosis and a high mortality rate, and represents up to 95% of all hypopharyngeal tumors. Patients with upper aerodigestive tract tumors can develop airway compromise before or during chemoradiotherapy. The present study aims to investigate the complication differences between elective tracheostomy and emergency-setting tracheostomy for patients with advanced hypopharyngeal squamous cell. The study group included 36 patients and analyzed the number and type of complications, functional outcomes and comparation of the laboratory testing in all the patients at 3 specific points (before tracheotomy, during the radiation therapy and at least 3 months after completion of radiation therapy). In addition, univariate analysis was performed in order to evaluate the prognosis of local control rates. The type and number of complications between elective and emergency-setting tracheostomy varied, but all the complications were resolved, and no hypoxic complications secondary to displacement of the tracheostomy tube or death cases related to the tracheostomy occurred. A total of 20/36 patients presented with complications, with 73% (16 patients) from the emergency tracheostomy cohort and 36% (4 patients) from the elective tracheostomy group. More than half of the elective tracheostomy (6/11 patients) responded favorably to the treatment, with a higher frequency than the patients with emergency tracheostomy (5/22 patients). The present study did not encounter significant statistical differences (P>0.05) of the treatment end-result regarding the type of tracheostomy performed, but the prediction analysis found for the patients aged under 60 years old, elective tracheostomy was associated with a higher chance of favorable treatment end result.

Is precision medicine the solution to improve organ preservation in laryngeal/hypopharyngeal cancer? A position paper by the Preserve Research Group.

In locally advanced (LA) laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC), larynx preservation (LP) strategies aim at the cure of the disease while preserving a functional larynx, thus avoiding total laryngectomy and the associated impact on the quality of life. In the last decades, apart from transoral and open-neck organ preservation approaches, several non-surgical regimens have been investigated: radiotherapy alone, alternate, concurrent or sequential chemoradiation, and bioradiotherapy. Despite major progress, the identification of reliable and effective predictors for treatment response remains a clinical challenge. This review examines the current state of LP in LA-LHSCC and the need for predictive factors, highlighting the importance of the PRESERVE trial in addressing this gap. The PRESERVE trial represents a pivotal initiative aimed at finding the optimal therapy for laryngeal preservation specific to each patient through a retrospective analysis of data from previous LP trials and prospectively validating findings. The goal of the PRESERVE trial is to develop a comprehensive predictive classifier that integrates clinical, molecular, and multi-omics data, thereby enhancing the precision and efficacy of patient selection for LP protocols.

Comparative analysis of organ preservation attempt and radical surgery in clinical T2N0 mid to low rectal cancer.

PURPOSE: Debate persists regarding the feasibility of adopting an organ-preserving strategy as the treatment modality for clinical T2N0 rectal cancer. This study aimed to compare the outcomes of attempting organ-preserving strategies versus radical surgery in patients with clinical T2N0 mid to low rectal cancer. METHODS: Patients diagnosed with clinical T2N0 rectal cancer, with lesions located within 8 cm from the anal verge as determined by pre-treatment magnetic resonance imaging between January 2010 and December 2020 were included. RESULTS: Of 119 patients, 91 and 28 were categorized into the organ-preserving attempt group and the radical surgery group, respectively. The median follow-up duration was 48.8 months (range, 0-134 months). The organ-preserving attempt group exhibited a reduced incidence of stoma formation (44.0% vs. 75.0%; p = 0.004) and a lower occurrence of grade 3 or higher surgical complications (5.8% vs. 21.4%; p = 0.025). Univariate analyses revealed no significant association between treatment strategy and 3-year local recurrence-free survival (organ-preserving attempt 87.9% vs. radical surgery 96.2%; p = 0.129), or 3-year disease-free survival (79.6% vs. 84.9%; p = 0.429). Multivariate analysis did not identify any independent prognostic factors associated with oncologic outcomes. CONCLUSION: Compared with radical surgery, attempted organ preservation resulted in lower incidences of stoma formation and severe surgical complications, whereas oncological outcomes were comparable. Attempting organ preservation may be a safe alternative to radical surgery for clinical T2N0 mid to low rectal cancer.

Alliance A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer.

BACKGROUND: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after TNT may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. METHODS: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N +) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N + vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (± 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 evaluable patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha = 0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse event rates. Biospecimens including archival tumor tissue, plasma and buffy coat, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and had accrued 330 patients as of May 2024. Study support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . DISCUSSION: Building on data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed The Janus Rectal Cancer Trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT05610163; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).