Reducing Salivary Toxicity with Adaptive Radiotherapy (ReSTART): A Randomized Controlled Trial Comparing Conventional IMRT to Adaptive IMRT in Head and Neck Squamous Cell Carcinomas.

BACKGROUND: The utility of Adaptive Radiotherapy (ART) in Head and Neck Squamous Cell Carcinoma (HNSCC) remains to be ascertained. While multiple retrospective and single-arm prospective studies have demonstrated its efficacy in decreasing parotid doses and reducing xerostomia, adequate randomized evidence is lacking. METHODS AND ANALYSIS: ReSTART (Reducing Salivary Toxicity with Adaptive Radiotherapy) is an ongoing phase III randomized trial of patients with previously untreated, locally advanced HNSCC of the oropharynx, larynx, and hypopharynx. Patients are randomized in a 1:1 ratio to the standard Intensity Modulated Radiotherapy (IMRT) arm {Planning Target Volume (PTV) margin 5 mm} vs. Adaptive Radiotherapy arm (standard IMRT with a PTV margin 3 mm, two planned adaptive planning at 10th and 20th fractions). The stratification factors include the primary site and nodal stage. The RT dose prescribed is 66Gy in 30 fractions for high-risk PTV and 54Gy in 30 fractions for low-risk PTV over six weeks, along with concurrent chemotherapy. The primary endpoint is to compare salivary toxicity between arms using salivary scintigraphy 12 months' post-radiation. To detect a 25% improvement in the primary endpoint at 12 months in the ART arm with a two-sided 5% alpha value and a power of 80% (and 10% attrition ratio), a sample size of 130 patients is required (65 patients in each arm). The secondary endpoints include acute and late toxicities, locoregional control, disease-free survival, overall survival, quality of life, and xerostomia scores between the two arms. DISCUSSION: The ReSTART trial aims to answer an important question in Radiation Therapy for HNSCC, particularly in a resource-limited setting. The uniqueness of this trial, compared to other ongoing randomized trials, includes the PTV margins and the xerostomia assessment by scintigraphy at 12 months as the primary endpoint.

Contralateral Nodal Relapse in Well-lateralised Oral Cavity Cancers Treated Uniformly with Ipsilateral Surgery and Adjuvant Radiotherapy With or Without Concurrent Chemotherapy: a Retrospective Study.

AIMS: To evaluate the incidence and pattern of contralateral nodal relapse (CLNR), contralateral nodal relapse-free survival (CLNRFS) and risk factors predicting CLNR in well-lateralised oral cavity cancers (OCC) treated with unilateral surgery and adjuvant ipsilateral radiotherapy with or without concurrent chemotherapy. MATERIALS AND METHODS: Consecutive patients of well-lateralised OCC treated between 2012 and 2017 were included. The primary endpoint was incidence of CLNR and CLNRFS. Univariable and multivariable analyses were carried out to identify potential factors predicting CLNR. RESULTS: Of the 208 eligible patients, 21 (10%) developed isolated CLNR at a median follow-up of 45 months. The incidence of CLNR was 21.3% in node-positive patients. CLNR was most common at level IB (61.9%) followed by level II. The 5-year CLNRFS and overall survival were 82.5% and 57.7%, respectively. Any positive ipsilateral lymph node (P = 0.001), two or more positive lymph nodes (P < 0.001), involvement of ipsilateral level IB (P = 0.002) or level II lymph node (P < 0.001), presence of extranodal extension (P < 0.001), lymphatic invasion (P = 0.015) and perineural invasion (P = 0.021) were significant factors for CLNR on univariable analysis. The presence of two or more positive lymph nodes (P < 0.001) was an independent prognostic factor for CLNR on multivariable analysis. CLNR increased significantly with each increasing lymph node number beyond two compared with node-negative patients. CONCLUSION: The overall incidence of isolated CLNR is low in well-lateralised OCC. Patients with two or more positive lymph nodes have a higher risk of CLNR and may be considered for elective treatment of contralateral neck.

Brachytherapy for Organ and Function Preservation in Soft-Tissue Sarcomas in Adult and Paediatric Patients.

Adjuvant radiotherapy is an integral component in the management of soft-tissue sarcomas. Brachytherapy is a very convenient and conformal way of delivering adjuvant radiotherapy in such tumours, which spares the surrounding normal tissue. Randomised studies have established the efficacy of brachytherapy in the adjuvant setting, with a 5-year local control of 80-85%. High dose rate, low dose rate and pulsed dose rate have shown equivalent local control, but high dose rate has gained popularity owing to patient convenience, radiation safety and flexibility in dose optimisation. Freehand insertion perioperative brachytherapy (intraoperative placement and postoperative treatment) is the most commonly used technique in soft-tissue sarcomas, with intraoperative radiotherapy and radioactive seed placement being the less commonly used techniques. Brachytherapy can be used as monotherapy or in combination with external beam radiotherapy, such as in cases of close/positive margins for safe dose escalation. Although the quantum of side-effects with external beam radiotherapy has considerably reduced with the evolution of technology and the introduction of intensity modulation (intensity-modulated radiotherapy), brachytherapy still scores better in terms of dose conformality, especially in recurrent tumours (previously irradiated) and when used to treat paediatric and geriatric patients.

Non-surgical organ preservation in laryngeal and hypopharyngeal cancers: an audit from the clinic.

BACKGROUND: There is increasing concern regarding efficacy of organ preservation protocol in laryngeal and hypopharyngeal cancers. METHOD: This study retrospectively assessed disease-related and functional outcomes of 191 patients with non-metastatic laryngeal or hypopharyngeal squamous cell carcinoma treated with curative intent (radiotherapy with or without chemotherapy). RESULTS: Seventy-six patients (39.8 per cent) had a primary cancer in the larynx, and 115 patients (60.2 per cent) had a primary cancer in the hypopharynx. The median follow up was 39 months. The 3-year time to progression, overall survival, local control and laryngectomy free survival was 56.2 per cent, 76.3 per cent, 73.2 per cent and 67.2 per cent, respectively. At the time of analysis, 83 patients (43.5 per cent) were alive and disease free at their last follow up and did not require tube feeding or tracheostomy. The laryngo-oesophageal dysfunction-free survival was 61 per cent at 3 years. CONCLUSION: Organ conservation protocols remain the standard of treatment in appropriately selected patients with laryngeal and hypopharyngeal cancers.

Effect of incorporation of soy protein isolate and inulin on quality characteristics and shelf-life of low-fat duck meat sausages.

OBJECTIVE: Low fat duck meat sausages were prepared by replacing the fat in the formulations with soy protein isolate (SPI) and inulin to find the best formulation having superior shelflife without affecting its quality attributes. METHODS: Four sausage mix formulations were prepared viz.control (0% SPI and inulin), T1 (2.5% inulin), T2 (2.5% SPI), and T3 (2.5% SPI+2.5% inulin) replacing duck fat as per the recipe. Five batches of duck meat sausages of each formulation were prepared, and the final products were evaluated for physico-chemical, organoleptic, and microbiological qualities. RESULTS: The % moisture and crude protein content of the sausages revealed an increasing trend (p<0.01) from control to the treated formulations, while the % total ash contents were found to be non-significant (p>0.05). On the contrary, the per cent ether extract decreased significantly (p<0.01) from the control to the treated groups. In terms of calorie value, control samples exhibited the highest values with a significant (p<0.01) regression from control to treated formulation, respectively. The colour profile study (L, a*, b*) of the formulations were found to be non-significant. Texture profile study in terms of springiness, cohesiveness, chewiness, and resilience revealed no significant difference in all the treatment groups except the hardness scores, which revealed a significantly (p<0.01) increasing trend from control to the treated formulations. The total viable count showed a significant decrease in the treated groups. However, there was a significant increase in the bacterial load during the storage till day 15th. The total viable psychrophilic bacterial count showed a significant (p<0.01) increase in bacterial load from day 5th to 15th day of storage. Colititre counts were negative for all the formulations until the 15th day of storage. CONCLUSION: The present study results may conclude that duck meat sausages could be prepared satisfactorily by replacing duck fat with SPI and inulin at the rate of 2.5% of each with superior quality attributes.

Outcomes of surgical versus non-surgical treatment of resectable T4a laryngeal and hypopharyngeal carcinoma.

OBJECTIVE: Surgery is the recommended treatment for resectable T4a laryngeal and hypopharyngeal carcinoma. Non-surgical treatment is an option in a select few patients. METHOD: This retrospective study was undertaken to assess the treatment outcomes in patients with resectable T4a carcinoma of the larynx and hypopharynx who received either surgical or non-surgical treatment at our institute and to assess factors influencing these outcomes. RESULTS: A total of 120 patients were included in the study. They were divided into groups A, B and C based on the presence of extralaryngeal spread through laryngeal membrane, cartilage or both. The overall survival was better among patients who received surgery than those who received non-surgical treatment in the three groups. The factor influencing overall survival was the treatment given in the form of surgical versus non-surgical treatment. CONCLUSION: Surgery is the preferred treatment for T4a laryngeal and hypopharyngeal carcinoma, even in patients with extralaryngeal spread without cartilage erosion.

Association of race and gender with primary caregiver relationships and eligibility for advanced heart failure therapies.

BACKGROUND: Caregiver support is considered necessary after heart transplant (HT) and left ventricular assist device (LVAD) for patients with end-stage heart failure (HF). Few studies have demonstrated how caregivers differ by gender and race, and whether that impacts therapy eligibility. METHODS: We examined caregiver relationships among 674 patients (32% women, 55% Black) evaluated at Emory University from 2011 to 2017. Therapy readiness was assessed using the Stanford Integrated Assessment for Transplant (SIPAT). Evaluation outcome according to caregiver relationship was compared using χ2 analysis. Multivariable logistic regression determined the association between caregiver and eligibility according to gender and race. RESULTS: Women and Black patients were less likely to have spouses as their support person (P < .001). Women were less likely to be considered eligible for advanced therapies (adjusted odds ratio [aOR] .64, 95% confidence interval [CI] .46-.89; P = .008), with Black women having lower eligibility than White women (aOR .28, 95% CI .11-.72; P = .008). Social support and SIPAT scores did not significantly influence eligibility by gender or race. CONCLUSION: Lack of caregiver support is considered a relative contraindication to advanced therapies. Type of caregiver in our cohort varied according to race and gender but did not explain differences in eligibility for advanced therapies.

Post-cricoid and Upper Oesophagus Cancers Treated with Organ Preservation Using Intensity-modulated Image-guided Radiotherapy: a Phase II Prospective Study of Outcomes, Toxicity and Quality of Life.

AIMS: To prospectively examine the outcomes, toxicity and quality of life (QoL) of patients with post-cricoid and upper oesophagus (PCUE) cancers treated with an organ-preservation approach of (chemo)-radiotherapy using intensity-modulated image-guided radiotherapy (IM-IGRT). MATERIALS AND METHODS: This phase II prospective study was conducted at a tertiary cancer centre from February 2017 to January 2020. Forty patients with squamous cell carcinoma of PCUE of stage T1-3, N0-2, M0 were accrued. Gross exolaryngeal extension/dysfunctional larynx were major exclusion criteria. Patients received 63-66 Gy in once-daily fractions using volumetric modulated arc therapy with daily IGRT. Outcome measures included disease-related outcomes, patterns of failure, Radiation Therapy Oncology Group toxicities, feeding tube dependency and QoL. RESULTS: The median follow-up was 22 months. Twenty-six (87.5%) patients had locoregionally advanced disease and 34 (85%) patients received (chemo)-radiotherapy. A complete response was observed in 26 (65%) patients. The 2-year locoregional control, event-free survival and cause-specific survival were 59.6%, 40.2% and 44.8%, respectively. The volume of primary tumour (GTVPvol) exceeding 28 cm3 had inferior overall survival (P = 0.005) on univariate analysis. Multivariable analysis showed GTVPvol and positron emission tomography-computed tomography maximum standardised uptake value to be independently predictive for event-free and overall survival. A feeding tube requirement at presentation was seen in 11 (27.5%) patients, whereas long-term feeding tube dependency at 6 months was seen in 10 (37%) patients. For QoL, a statistical improvement in pain, appetite loss and swallowing was observed over time. CONCLUSION: Although the outcomes of PCUE cancers remain dismal, the use of state of the art diagnostic modalities, careful case selection and modern radiotherapy techniques improved outcomes as compared with before in this exclusive analysis of PCUE cancers.

Salvage radiotherapy for postoperative locoregional failure in esophageal cancer: a systematic review and meta-analysis.

Locoregional recurrences following surgery for esophageal cancers represent a significant clinical problem with no standard recommendations for management. We conducted this systematic review and meta-analysis with the objective of studying safety and efficacy of salvage radiotherapy in this setting. All prospective and retrospective cohort studies, which studied patients who developed locoregional recurrence following initial radical surgery for esophageal cancer and subsequently received salvage radiation therapy (RT)/chemoradiation with all relevant information regarding survival outcome and toxicity available, were included. The quality of eligible individual studies was assessed using the Newcastle-Ottawa Scale score for risk of bias. R package MetaSurv was used to obtain a summary survival curve from survival probabilities and numbers of at-risk patients collected at various time points and to test the overall heterogeneity using the I2 statistic. Thirty studies (27 retrospective, 3 prospective) published from 1995 to 2020 with 1553 patients were included. The median interval between surgery and disease recurrence was 12.5 months. The median radiation dose used was 60 Gy and 57% received concurrent chemotherapy. The overall incidence of acute grade 3/4 mucositis and dermatitis were 8 and 4%, respectively; grade 3/4 acute pneumonitis was reported in 5%. The overall median follow-up of all studies included was 27 months. The 1-, 2- and 3-year overall survival (OS) probabilities were 67.9, 35.9 and 30.6%, respectively. Factors which predicted better survival on multivariate analysis were good PS, lower group stage, node negativity at index surgery, longer disease-free interval, nodal recurrence (as compared to anastomotic site recurrence), smaller disease volume, single site of recurrence, RT dose >50 Gy, conformal RT, use of concomitant chemotherapy and good radiological response after radiotherapy. Salvage radiotherapy with or without concomitant chemotherapy for locoregional recurrences after surgery for esophageal cancer is safe and effective. Modern radiotherapy techniques may improve outcomes and reduce treatment-related morbidity.

A unified approach to design controller in cascade control structure for unstable, integrating and stable processes.

This article presents a unified approach of controller design in cascade control structure (CCS) for unstable, integrating and stable processes with dead-time to achieve enhanced load disturbance rejection. The design of inner and outer loop controllers in CCS is based, partially on the direct synthesis approach and partially on the pole placement method. First, the parameters of the inner loop controller are obtained and then the outer loop controller is designed by considering the inner loop as a part of the primary plant. The proposed design approach deals with a wide range of processes having unstable, integrating and stable dynamics in a unified way. It is applied directly on the higher and lower order processes, as the proposed strategy is acquitted from the approximation of the dead-time and model order reduction of the plant. Simulations have been conducted to show the efficacy of the present approach. The results shows that the present approach provides enhanced regulatory performance as compared to the recently reported approaches from the literature.

The Practice of Paediatric Radiation Oncology in Low- and Middle-income Countries: Outcomes of an International Atomic Energy Agency Study.

AIMS: Childhood cancer survival is suboptimal in most low- and middle-income countries (LMICs). Radiotherapy plays a significant role in the standard care of many patients. To assess the current status of paediatric radiotherapy, the International Atomic Energy Agency (IAEA) undertook a global survey and a review of practice in eight leading treatment centres in middle-income countries (MICs) under Coordinated Research Project E3.30.31; 'Paediatric radiation oncology practice in low and middle income countries: a patterns-of-care study by the International Atomic Energy Agency.' MATERIALS AND METHODS: A survey of paediatric radiotherapy practices was distributed to 189 centres worldwide. Eight leading radiotherapy centres in MICs treating a significant number of children were selected and developed a database of individual patients treated in their centres comprising 46 variables related to radiotherapy technique. RESULTS: Data were received from 134 radiotherapy centres in 42 countries. The percentage of children treated with curative intent fell sequentially from high-income countries (HICs; 82%) to low-income countries (53%). Increasing deficiencies were identified in diagnostic imaging, radiation staff numbers, radiotherapy technology and supportive care. More than 92.3% of centres in HICs practice multidisciplinary tumour board decision making, whereas only 65.5% of centres in LMICs use this process. Clinical guidelines were used in most centres. Practice in the eight specialist centres in MICs approximated more closely to that in HICs, but only 52% of patients were treated according to national/international protocols whereas institution-based protocols were used in 41%. CONCLUSIONS: Quality levels in paediatric radiotherapy differ among countries but also between centres within countries. In many LMICs, resources are scarce, coordination with paediatric oncology is poor or non-existent and access to supportive care is limited. Multidisciplinary treatment planning enhances care and development may represent an area where external partners can help. Commitment to the use of protocols is evident, but current international guidelines may lack relevance; the development of resources that reflect the capacity and needs of LMICs is required. In some LMICs, there are already leading centres experienced in paediatric radiotherapy where patient care approximates to that in HICs. These centres have the potential to drive improvements in service, training, mentorship and research in their regions and ultimately to improve the care and outcomes for paediatric cancer patients.

Sex differences in eligibility for advanced heart failure therapies.

OBJECTIVES: We investigated sex-based differences in eligibility for and outcomes after receipt of advanced heart failure (HF) therapies. BACKGROUND: Although women are more likely to die from HF than men, registry data suggest that women are less likely to receive heart transplant (HT) or left ventricular assist device (LVAD) for largely unknown reasons. METHODS: We performed a single-center retrospective cohort study of patients evaluated for advanced HF therapies from 2012 to 2016. Logistic regression was used to determine the association of sex with eligibility for HT/LVAD. Competing risks and Kaplan-Meier analysis were used to examine survival. RESULTS: Of 569 patients (31% women) evaluated, 223 (39.2%) were listed for HT and 81 (14.2%) received destination (DT) LVAD. Women were less likely to be listed for HT (adjusted odds ratio [OR] 0.36, 95% confidence interval [CI] 0.21-0.61; P < .0001), based on allosensitization (P < .0001) and obesity (P = .02). Women were more likely to receive DT LVAD (adjusted OR 2.29, 95% CI 1.23-4.29; P = .01). Survival was similar between men and women regardless of whether they received HT and DT LVAD or were ineligible for therapy. CONCLUSION: Women are less likely to be HT candidates, but more likely to receive DT LVAD.

Validating patient prioritization in the 2018 Revised United Network for Organ Sharing Heart Allocation System: A single-center experience.

The 2018 Revised United Network for Organ Sharing Heart Allocation System (HAS) was proposed to reclassify status 1A candidates into groups of decreasing acuity; however, it does not take into account factors such as body mass index (BMI) and blood group which influence waitlist (WL) outcomes. We sought to validate patient prioritization in the new HAS at our center. We retrospectively evaluated patients listed for heart transplantation (n = 214) at Emory University Hospital from 2011 to 2017. Patients were reclassified into the 6-tier HAS. Multistate modeling and competing risk analysis were used to compare outcomes of transplantation and WL death/deterioration between new tiers. Additionally, a stratified sensitivity analysis by BMI and blood group was performed. Compared with tier 4 patients, there was progressively increasing hazard of WL death/deterioration in tier 3 (HR: 2.52, 95% CI: 1.37-4.63, P = .003) and tier 2 (HR: 5.03, 95% CI: 1.99-12.70, P < .001), without a difference in transplantation outcome. When stratified by BMI and blood group, this hierarchical association was not valid in patients with BMI ≥30 kg/m2 and non-O blood groups in our cohort. Therefore, the 2018 HAS accurately prioritizes the sickest patients in our cohort. Factors such as BMI and blood group influence this relationship and iterate that the system can be further refined.

Taxane-based Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Nasopharyngeal Carcinoma: Prospective Results from a Non-endemic Cohort.

AIMS: To report the outcomes of induction chemotherapy (ICT) followed by chemoradiotherapy (CTRT) for a large cohort of locoregionally advanced nasopharyngeal cancer (LA-NPC) from a non-endemic region. MATERIALS AND METHODS: Between January 2008 and July 2015, 201 patients with histologically proven, non-metastatic NPC were treated with ICT followed by CTRT at our institute. All the patients received two to three cycles of a taxane-based ICT regimen. Radiotherapy was delivered using an intensity-modulated radiotherapy (IMRT) technique in all patients. RESULTS: After a median follow-up of 37 months (range: 7-110 months), the 3-year disease-free survival (DFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival of the entire cohort was 72, 85, 83 and 87.4%, respectively. On multivariate analysis, histology was an independent predictor of DFS, LRFS and overall survival, with keratinising squamous cell carcinoma histologies predicting a worse outcome. The nodal stage was an independent predictor of DFS, DMFS and overall survival. Age, gender, ethnicity, tumour stage and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 19% of patients at last follow-up and grade 2 or worse xerostomia was seen in 24% of patients. Thirty-nine per cent of patients developed clinical hypothyroidism at last follow-up. CONCLUSION: ICT followed by concurrent CTRT in the IMRT era provides excellent locoregional control, distant control and overall survival rates in patients with LA-NPC. However, distant failure continues to be a problem and may require further systemic intensification.

Decisional regret in left ventricular assist device patient-caregiver dyads.

BACKGROUND: The objective of this study was to investigate decisional regret among left ventricular assist device (LVAD) patients and their caregivers. METHODS: This study was a single center, cross-sectional survey of patients after LVAD implantation and their caregivers. Subjects were recruited at their outpatient heart failure appointments. Patients and caregivers at least three months from LVAD implantation completed a 5-item, validated decisional regret scale. Summative scores on a 0-100 point scale were determined for patient and caregivers (0 = no regret). Subgroup analysis included gender, LVAD indication (bridge to transplant (BTT) or destination therapy (DT)), time from LVAD implantation, and caregiver relationship. Dyad discordance was defined as a patient-caregiver difference of ≥2 points on any regret scale question. RESULTS: Fifty patients were approached for participation. Thirty-three LVAD patient-caregiver dyads were enrolled in the study (19 male, 14 female patients; 8 male, 25 female caregivers). Patients had a mean age of approximately 50 years. Caregivers had a mean age of approximately 54 years. Patients had a median regret score of 10 (Interquartile range (IQR): 0-30), while caregivers had a median regret score of 20 (IQR: 0-25). Median regret scores of female patients were significantly higher than that of male patients (27.5 vs 0, p = 0.0038). BTT patients had numerically lower regret than DT patients, but this was not statistically significant. Patients who had been implanted for greater than three years had the highest regret scores. Discordance in at least one domain of the regret scale was present in 19 out of 33 (57.6%) dyads. CONCLUSIONS: While decisional regret was reasonably low in this population, comparatively, there was significantly increased decisional regret among female patients and patients further from LVAD implantation. Differences between patients and caregivers were also observed. These findings highlight the need for robust support and continual attention to expectations before and after LVAD implantation.

Oropharyngeal Cancers in the East and the West - Implications of Aetiopathogenesis on Prognosis and Research.

There has been a surge in human papillomavirus (HPV)-positive oropharyngeal cancers (OPCs) in the West. Although the prognosis of HPV-positive OPC is good, de-escalation strategies have so far not been able to confirm comparable cancer control. We examine the strategies implemented across the globe to safely reduce toxicities in HPV-positive disease. HPV-negative OPC has a poorer prognosis and is more prevalent in Eastern countries. We outline the intensification strategies currently used in HPV-negative cancers, with an aim to better prognosis. With recent improvements in clinical trial frameworks in Eastern countries such as India, we discuss areas where joint collaborative research between Western and Eastern countries could further improve outcomes in OPC.

Oral Cavity Cancer in the Indian Subcontinent - Challenges and Opportunities.

Oral cavity cancer (OCC) poses a global challenge that plagues both the Orient and the Occident, accounting for an estimated 350 000 new cases and 177 000 deaths in 2018. OCC is a major public health problem in the Indian subcontinent, where it ranks among the top three cancer types in both incidence and mortality. Major risk factors are the use of tobacco, betel quid and alcohol consumption. OCC is a heterogeneous group of multiple histologies that affects multiple subsites. The oral cavity includes the lips, buccal mucosa, teeth, gingiva, anterior two-thirds of the tongue, floor of the mouth and hard palate. OCC is defined as cancer of lips, mouth and tongue as defined by the International Classification of Diseases coding scheme. The epidemiology, aetio-pathogenesis and treatment philosophy are similar within this group. Although salivary gland malignancies, sarcomas, mucosal melanomas and lymphomas can also arise within the oral cavity, this review will focus on squamous cell cancer, which is the predominant histology in OCC. We review and contrast data from developing and developed countries. We also highlight the unique regional challenges that countries in the East face; citing India as an example, we elaborate on the opportunities and scope for improvement in the management of OCC.

Mortality in status 2 patients listed for heart transplantation in the United States: Will understanding cause of death help justify implantation of left ventricular assist devices into less sick patients?

OBJECTIVE: It remains unclear whether left ventricular assist device (LVAD) implantation in non-inotrope dependent patients is of clinical benefit. This study sought to evaluate cause of death in patients listed for heart transplant (HT) to determine the relative risks and benefits of implanting LVAD into patients who are less sick than those included in the original clinical trials. METHODS: We examined death as the primary outcome in 23,098 patients listed for HT from 2006 to 2014 using proportional subdistribution hazards modeling. Cause of death was examined as a secondary outcome using χ2 tests. RESULTS: 1859 (8.1%) patients were removed from the wait list for death, including 229 (2.7%) status 1A, 349 (4.6%) status 1B, 246 (13.2%) status 2, and 1035 (26.0%) status 7 patients (P < 0.0001). Status 2 patients who received LVAD while listed had a higher risk of death compared to those who did not (adjusted HR 1.68; 95% CI 1.09-2.59; P = 0.02), while there was no increased risk of death in status 1A (HR 1.02; 95% CI 0.68-1.51; P = 0.9) and status 1B (HR 0.89; 95% CI 0.65-1.23; P = 0.5) who received LVAD. Status 2 patients who received LVAD were more likely to die cerebrovascular causes (0.6% vs. 0.1%, P = 0.009) and organ failure (70.6% vs. 29.4%, P = 0.003). CONCLUSIONS: LVAD implantation in status 2 patients listed for HT is associated with a higher risk of death. More research is needed to determine the impact LVAD implantation will have on mortality in patients with ambulatory, non-inotrope dependent HF.