Infirm Patients Research Articles

Virtual Reality Videos for Symptom Management in Hospice and Palliative Care

ObjectiveTo learn more about the effect of virtual reality videos on patients’ symptoms near the end of life, including which are most effective, how long the effect lasts, and which patients benefit the most. Patients and MethodsWe conducted a prospective study of 30 patients in a regional hospice and palliative care program from March 11, 2022, through July 14, 2023. Using a head-mounted display virtual reality, all participants viewed a 15-minute video of serene nature scenes with ambient sounds. Fifteen patients also participated in a second session of viewing bucket-list video clips they selected. Symptoms were measured with the revised Edmonton Symptom Assessment Scale before, immediately after, and 2 days after each experience. Participants rated their bucket-list selections by level of previous experience, strength of connection, and overall video quality. Functional status was also recorded. ResultsNature scenes significantly improved total symptom scores (30% decrease, P<.001), as well as scores for drowsiness, tiredness, depression, anxiety, well-being, and dyspnea. The improved scores were not sustained 2 days later. Overall, bucket-list videos did not significantly improve symptoms. Neither previous experience with an activity nor a strong connection correlated with significant improvement; however, when patients rated video quality as outstanding, scores improved (31% decrease, P=.03). Patients with lower functional status tended to have more symptoms beforehand and improve the most. ConclusionSerene nature head-mounted display virtual reality scenes safely reduce symptoms at the end of life. Bucket-list experiences may be effective if they are high-quality. More infirm patients may benefit the most.

THE MANAGEMENT OF OSTEOPOROTIC VERTEBRAL FRACTURES AT A DISTRICT GENERAL HOSPITAL

IntroductionMost common osteoporotic fracture20-30% of patients with OVFs are presented to hospital while 2.2 million remain undiagnosed, as diagnosis is usually opportunistic66,000 OVFs occur annually in the UK with increase by 18,000 cases a year until 2025.20% chance of another OVF in next 12 months and 3 times risk of hip fracture.Acute painful OVFs poorly tolerated by infirm elderly patients, leading to significant morbidity and 8 times increase in age-adjusted mortality.Materials and MethodsClassify fracture severity and patents with ovfs in 12-month period.To assess follow-up status and if kyphoplasty was offered within 6 weeks as per NICE guidelines.To introduce Royal Osteoporosis Society and GIRFT guidelines on management of symptomatic osteoporotic vertebral fracturesResultsTotal no. of patients- 62Initial pain assessment=40Pain assessed at ≤6 weeks- 21Duration from decision to operate to kyphoplasty 8.7 weeks.11% had kyphoplasty of which 50% noted improvement in pain.11 deathsNearly similar findings to NoSH studyConclusionTo improve pain assessment on admission of patients with acute osteoporotic vertebral fractures.To follow GIRFT guidelines for early assessment and intervention in patients with acute osteoporotic vertebral fractures to improve pain, mobility and early discharge from hospital.Conflicts of interestNoneSources of fundingNone

Interim Results of a Phase I/II Study of Intermediate-Dose Post-Transplantation Cyclophosphamide after Reduced Intensity Conditioned HLA-Matched Bone Marrow Transplantation for Older or Infirm Patients

Interim Results of a Phase I/II Study of Intermediate-Dose Post-Transplantation Cyclophosphamide after Reduced Intensity Conditioned HLA-Matched Bone Marrow Transplantation for Older or Infirm Patients

Higher Risk Hospital Based Maxillofacial Sedation for ASA 3 and ASA 4 Patients using Propofol Based Target Controlled Infusions

There is a paucity of information regarding the administration of Target Controlled Infusion (TCI) sedation to American Society of Anesthesiology (ASA) class 3 and 4 patients for maxillofacial procedures. We report a selection of ASA 3 and ASA 4 patients who recently underwent dental extractions by maxillofacial surgeons and were managed under TCI propofol sedation in mainstream hospital settings. The utilisation of effective TCI propofol sedation, accompanied by an ultra short-acting narcotic (either alfentanil or remifentanil) given immediately prior to the administration of local anaesthetic (LA) by the surgeon, permits the avoidance of higher risk general anesthesia and its associated complications within this more infirm patient group. Effective use of TCI sedation in ASA 3 and ASA 4 maxillofacial patients requires the provision of skills routinely employed for sedation in healthy patients, with the appropriate dosage modifications necessitated by age and associated patient co-morbidities. Properly administered in a hospital setting, TCI sedation with propofol accompanied with an ultra-short acting narcotic is safe and effective.

Real-World Outcomes for Primary CNS Lymphoma from a Single Academic Institution: The Augusta Experience

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive, non-hodgkin lymphoma, characterized by exclusive confinement to the central nervous system. Outcomes are poor, with a 5 year overall survival of 30% with standard induction of high-dose-methotrexate (HD-MTX) based regimens followed by consolidation. Barring epidemiologic trends due to immunodeficiency disorders, PCNSL is a disease of the immunocompetent older patient (age &amp;gt;60 years). Incidence in those aged &amp;gt;70 years is 10 times higher than the general population. The overall survival hasn't significantly changed in 4 decades. We present retrospective data in a rural, elderly population in Georgia. Methods: We reviewed all patients diagnosed with PCNSL at our institution from January 1, 2013 to January 1, 2023. A retrospective chart review was conducted to assess for demographic factors, comorbidities, organ dysfunction, induction regimens, and consolidation treatments influencing patient care. Results: A total of 38 PCNSL patients were identified. 6 died and one was lost to follow-up prior to start of therapy and are not further analyzed here. All patients had DLBCL histology. The median age was 62.3 (21-82 years) with 54.8% male. Patients identified as non-Hispanic white (77.4%), African-American (9.68%), Asian (6.46%), Hispanic or Latino (3.23%), and multiracial (3.23%). The youngest patient aged 21 years had HIV/AIDS. 2 of 3 patients diagnosed in their 30s were on immunosuppression, for renal transplant and multiple sclerosis. No patients had hepatitis B or C. Medical comorbidities were common with 80.7% of patients having at least one which included HTN, TIIDM, history of CVA or CAD, and atrial fibrillation. 19.4% of patients had impaired renal function (CrCl &amp;lt;60 ml/min). Several patterns emerged when stratified by best treatment response at end of induction (EOI). Median follow-up was 12 mos (range: 0-66). Age, HIV status, gender, CrCl, positive CSF at baseline, or elevated LDH were not statistically significant predictors of response. This is probably due to the small sample size and missing data. Seizures at disease outset were associated with a statistically significant worse response to induction and all patients without seizures responded. This is likely a proxy for deep brain involvement and data are similar to CALGB 50202 where deep brain lesions independently correlated with a shorter progression-free-survival. Completion of ≥ 6 cycles of induction and a lower MTX level at discharge were predictors for response likely reflective of better organ function. Majority of patients with progressive disease received fewer than 6 cycles. A poorer EOI ECOG PS portended a worse response and all responders maintained an EOI PS of 0-2. Peak MTX level did not correlate with response. Sample size was too small to discriminate between discharge MTX thresholds of &amp;lt;0.05 vs 0.1 vs &amp;gt;0.15 however that will be an area of further investigation. Choice of induction regimen did not predict response statistically, however, all responders received HD-MTX-based combination chemotherapy (77.42%). 19.4% received HD-MTX alone and 3.2% received rituximab monotherapy. Only 8 (25.8%) of patients received consolidation. 7 received non-myeloablative therapy with 2 receiving additional WBRT and 1 patient received WBRT alone. Conclusion: PCNSL remains an area of high unmet need. Recently, IELSG43 and MARTA studies have shown that HD-MTX-based combination chemoimmunotherapy followed by autologous stem cell transplant leads to improved outcomes regardless of age; however, non-relapse mortality remains a concern. Our data comprising chiefly of an elderly cohort reiterate efficacy of combination chemo-immunotherapy and impact of number of induction cycles on response, despite age. Most common reasons for treatment discontinuation included performance status deterioration and death from disease or toxicity. A multidisciplinary approach with physical therapy, nutritionist, neurology, and geriatrics would be optimal, particularly for older and infirm patients. In addition, alternatives to consolidation such as targeted agent (e.g. Bruton tyrosine kinase inhibitor) maintenance should be considered to improve outcomes in the elderly. One patient at our center is receiving post-induction zanubrutinib with a complete remission to date (~16 mos). This will be a focus for a phase II clinical trial at our institution.

An 8-year pragmatic observation evaluation of the benefits of allogeneic HCT in older and medically infirm patients with AML

AbstractWe designed a prospective, observational study enrolling patients presenting for treatment of acute myeloid leukemia (AML) at 13 institutions to analyze associations between hematopoietic cell transplantation (HCT) and survival, quality of life (QOL), and function in: the entire cohort, those aged ≥65 years, those with high comorbidity burden, intermediate cytogenetic risk, adverse cytogenetic risk, and first complete remission with or without measurable residual disease. Patient were assessed 8 times over 2 years. Time-dependent regression models were used. Among 692 patients that were evaluable, 46% received HCT with a 2-year survival of 58%. In unadjusted models, HCT was associated with reduced risks of mortality most of the subgroups. However, after accounting for covariates associated with increased mortality (age, comorbidity burden, disease risks, frailty, impaired QOL, depression, and impaired function), the associations between HCT and longer survival disappeared in most subgroups. Although function, social life, performance status, and depressive symptoms were better for those selected for HCT, these health advantages were lost after receiving HCT. Recipients and nonrecipients of HCT similarly ranked and expected cure as main goal of therapy, whereas physicians had greater expectations for cure than the former. Accounting for health impairments negates survival benefits from HCT for AML, suggesting that the unadjusted observed benefit is mostly owing to selection of the healthier candidates. Considering patients’ overall expectations of cure but also the QOL burdens of HCT motivate the need for randomized trials to identify the best candidates for HCT. This trial was registered at www.clinicaltrials.gov as #NCT01929408.

Benign Peripheral Non-cranial Nerve Sheath Tumors of the Neck.

Benign peripheral non-cranial nerve sheath tumors are rare lesions, including both schwannomas and neurofibromas. These tumors arise from Schwann cells, and may originate from any peripheral, cranial, or autonomic nerve. Most of them are localized and sporadic but multifocal systemic forms can occur. Cervical sympathetic chain, brachial plexus, cervical plexus and spinal roots and nerves are the major nerve systems commonly affected. Dumbbell-shaped intra- and extradural tumors occur most commonly in the cervical spine, as well as purely extradural and paravertebral tumors. The management of these tumors has improved greatly owing to the developments in imaging techniques and surgical innovations such as endoscopically assisted approaches and robotic surgery. Microsurgical intracapsular excision of the tumor helped by the use of intraoperative fluorescent dyes and intraoperative neurophysiological monitoring minimize postoperative neural deficit, since most schwannomas are encapsulated. Most tumors can be removed with a low rate of complications and recurrence. Radiotherapy should be considered for growing lesions that are not amenable to surgery. In asymptomatic patients, observation and serial scans is an option for elderly infirm patients.

Surgeons Consider Initial Nonoperative Treatment With Potential for Future Conversion to Reverse Arthroplasty a Reasonable Option for Older, Relatively Infirm, and Less-Active Patients.

Two recent developments favor initial nonoperative treatment of proximal humerus fractures among the older, relatively infirm, less-active patients that represent most patients with such fractures: (1) evidence of minimal benefit of open reduction, internal fixation over nonoperative treatment, and (2) evidence of the effectiveness of the reverse total shoulder arthroplasty. As one step in determining the feasibility of a strategy of initial nonoperative treatment of proximal humerus fracture among older, relatively infirm, less-active people, we performed a survey-based experiment to measure factors associated with surgeon recommendation for initial nonoperative treatment. Members of the Science of Variation Group viewed 8 hypothetical patients with radiographs of complex proximal humeral fractures and 7 randomized patient variables. For each scenario, surgeons were asked whether they would recommend (1) initial nonoperative treatment with bailout reverse arthroplasty or (2) immediate reverse arthroplasty. The mean percentage of recommendations for initial nonoperative treatment was 63%, with wide variation by surgeon (range 0%-100%). In multilevel mixed-effects logistic regression, recommendation for initial nonoperative treatment was associated with specific radiographs, older age, having a comorbidity, being homebound, surgical subspecialists, and more than 20 years in practice. These findings suggest that surgeons may consider initial nonoperative treatment with potential for future conversion to reverse arthroplasty an acceptable treatment option, particularly for older, less-active, more infirm individuals, and relatively less displaced fractures with little comminution.

Effect of an Acute Insect Preload vs. an Almond Preload on Energy Intake, Subjective Food Consumption and Intestinal Health in Healthy Young Adults.

Protein is considered the most satiating macronutrient, and its effect on satiety and food intake is source-dependent. For the first time, we compared the effect of the administration of an insect or almond preload, both containing 20 g of protein, on appetite and food intake in human subjects. Participants consumed both foods and a vehicle as a liquid preload on three separate days. They were then offered a breakfast and lunch buffet meal at which food intake was measured. Visual analogue scale (VAS) questionnaires were completed following the three preloads to assess appetite and other sensations. At breakfast, reduced energy intake was observed for both preloads compared with vehicle. At lunch, food intake only differed in the insect group, which consumed more than the vehicle. Insect preload increased the total amount of protein ingested with a slight increase in total energy consumed, differently than almond, which significantly increased total protein and energy consumed. There was no correlation between indigestion-sensation ratings and food intake. Moreover, the insect preload resulted in lower sleepiness and tiredness ratings compared with the almond preload. Thus, insect-derived protein may be suitable as a safe ingredient for snacks intended for elderly or infirm patients who require increased protein intake.

Updated Outcomes of Split Course Radiotherapy in Elderly or Infirm Patients With Advanced Cancers of the Head and Neck.

Head and neck cancers are often treated with extended courses of radiotherapy (RT), which may prove excessively toxic for frail patients. Split course RT (SCRT) delivers two courses of RT separated by 4-6 weeks, personalizing treatment intensity based on response. In this study, we present our updated experience using this technique. From a single institution database, we identified patients considered for SCRT. For patients undergoing a second course of RT, cumulative incidence of locoregional recurrence (LRR) and overall survival (OS) are reported. A total of 98 patients were included, of whom seventy-five percent underwent a second course of RT. The most common fractionation was 30 Gy in 10 fractions for each course, with a median cumulative dose of 60 Gy. In those undergoing a second course of RT, median OS was 9.7 months and cumulative incidence of LRR at 6, 12, and 24 months was 17.0%, 23.1%, and 29.4%, respectively. SCRT offers an attractive treatment paradigm to personalize radiation intensity based on patient tolerance, while maintaining reasonable safety and efficacy in those unfit for standard full course RT.

The Measurable Residual Disease Status of Acute Myeloid Leukemia in First Complete Remission at Allogeneic Hematopoietic Cell Transplantation Interacts with Conditioning Intensity to Predict Outcome

BACKGROUND: Allogeneic hematopoietic cell transplant (allo-HCT) is offered to selected patients with acute myeloid leukemia (AML) in first complete remission (CR1). Despite overall survival (OS) benefits compared to non-HCT therapy, transplant related mortality (TRM) & relapse incidence (RI) remain obstacles. Reduced intensity (RIC) & non-myeloablative (NMA) conditioning regimens have reduced early toxicity & permit extension of allo-HCT to older or infirm patients but RI offsets this benefit. Disease status at allo-HCT predicts subsequent relapse. Patients with AML CR1 & measurable residual disease (MRD POS) have a higher RI than those who are MRD NEG. We hypothesised that in AML CR1, MRD status would interact with conditioning intensity to predict survival & toxicity in patients <50y & ≥50y. METHODS: This was a multicentre, retrospective registry study by the Acute Leukemia Working Party of the European Society for Blood & Bone Marrow Transplantation. Eligibility: Age ≥18y, first allo-HCT 2000-15, diagnosis of AML with a molecular marker, CR1 & availability of MRD status (polymerase chain reaction / immunophenotyping as per center policy), peripheral blood stem cells (PBSC) or bone marrow (BM) from a matched related (MRD), volunteer unrelated (VUD) or haplo-identical donor.Univariate & Cox Regression multivariate analyses (MVA) were applied to data. Measured outcomes included 2y OS, leukemia free survival (LFS), non-relapse mortality (NRM), graft vs host disease (GVHD) & GVHD-free/relapse-free survival (GRFS).RESULTS: A total of 2292 patients, 1192 male, were eligible. Conditioning intensity was high intensity “myeloablative” (MAC) in 1254 (55%), RIC in 867 (38%) & NMA in 171 (7%). Patients were defined by age, MRD status & conditioning. This yielded 4 paired groups of patients: <50y MRD POS MAC (N=240) vs RIC/NMA (N=58); <50y MRD NEG MAC (N=665) vs RIC/NMA (N=195); ≥50y MRD POS MAC (N=126) vs RIC/NMA (N=230) & ≥50y MRD NEG MAC (N=223) vs RIC/NMA (N=555). Groups were comparable for the following parameters: Cytogenetic risk groups (intermediate in 71% & high risk in 29%); FLT3 or NPM1 mutation status (reported in 55% & 45%); CR rate with first induction (69% & reported in 1706 [74%]). While donor source & gender were also comparable, there was significantly greater use of PBSC than BM within all groups. In vivo T-cell depletion (TCD) was used in 46% & 59% of MAC & RIC allo-HCT overall & retained significance within all paired groups.Univariate analysis of all patients confirmed the predictive effect of MRD status on allo-HCT outcomes. Patients <50y & MRD POS benefited from MAC vs NMA/RIC allo-HCT with RI 36.6% vs 50.7% (P=0.013), LFS 49% vs 36.5% (P=0.004), OS 59.4% vs 43.7% (P=0.008) & GRFS 35.3% vs 28.2% (P=0.025). In contrast, patients who were <50y MRD NEG, ≥50y MRD POS or ≥50y MRD NEG derived no survival benefits from MAC compared to RIC/NMA allo-HCT.Next, Cox regression analysis was performed, adjusting for age by decade, cytogenetic risk, stem cell source, donor & TCD. In <50y MRD POS, RIC/NMAwas inferior to MAC for RI (HR 1.7 CI 1.05-2.79) & LFS (HR 1.6 CI 1.01-2.40) with a trend to lower OS. Use of TCD reduced acute GVHD grades III-IV (HR 0.32 CI 0.12-0.843).In <50y MRD NEG, RIC/NMA & MAC allo-HCT had equivalent RI, NRM, LFS & OS but less chronic GVHD following RIC/NMA regimens (HR 0.7 CI 0.52- 0.99). Adverse factors in this group were poor risk cytogenetics (impacting RI, LFS & OS) & use of VUD vs MRD, associated with higher aGVHD & cGVHD rates. TCD conferred reduced GVHD & LFS without significant effect on OS. Use of PBSC increased NRM & GVHD toxicity without significant effect on LFS or OS.In ≥50y MRD POS patients, RI, NRM, LFS & OS were unaffected by conditioning intensity. Poor risk cytogenetics exerted adverse effects on RI (HR 1.8 CI 1.26-2.57), LFS (HR 1.7 CI 1.28-2.31) & OS (HR 1.8 CI 1.32-2.47). Increasing recipient age associated with increased risk of aGVHD (III-IV) (HR 3.2 CI 1.36 - 7.61) but no other parameter altered outcome.In ≥50y MRD NEG patients, no benefits accrued to MAC for RI, NRM, LFS & OS & there was a trend to lower NRM in RIC/NMA (HR 0.7 CI 0.48-1.03). TCD increased RI & reduced NRM & GRFS without effect on LFS or OS.CONCLUSION: MAC allo-HCT benefits <50y MRD POS patients. RIC allo-HCT may be sufficient for other groups. Procedural toxicity may be reduced further by in vivo TCD. MRD impact on allo-HCT needs prospective evaluation & standardization of molecular & immunophenotyping assays. DisclosuresMohty:Sanofi: Honoraria, Speakers Bureau. Savani:Jazz Pharmaceuticals: Speakers Bureau.

Multisite 11-year experience of less-intensive vs intensive therapies in acute myeloid leukemia

AbstractLess-intensive induction therapies are increasingly used in older patients with acute myeloid leukemia (AML). Using an AML composite model (AML-CM) assigning higher scores to older age, increased comorbidity burdens, and adverse cytogenetic risks, we defined 3 distinct prognostic groups and compared outcomes after less-intensive vs intensive induction therapies in a multicenter retrospective cohort (n = 1292) treated at 6 institutions from 2008 to 2012 and a prospective cohort (n = 695) treated at 13 institutions from 2013 to 2017. Prospective study included impacts of Karnofsky performance status (KPS), quality of life (QOL), and physician perception of cure. In the retrospective cohort, recipients of less-intensive therapies were older and had more comorbidities, more adverse cytogenetics, and worse KPS. Less-intensive therapies were associated with higher risks of mortality in AML-CM scores of 4 to 6, 7 to 9, and ≥10. Results were independent of allogeneic transplantation and similar in those age 70 to 79 years. In the prospective cohort, the 2 groups were similar in baseline QOL, geriatric assessment, and patient outcome preferences. Higher mortality risks were seen after less-intensive therapies. However, in models adjusted for age, physician-assigned KPS, and chance of cure, mortality risks and QOL were similar. Less-intensive therapy recipients had shorter length of hospitalization (LOH). Our study questions the survival and QOL benefits (except LOH) of less-intensive therapies in patients with AML, including those age 70 to 79 years or with high comorbidity burdens. A randomized trial in older/medically infirm patients is required to better assess the value of less-intensive and intensive therapies or their combination. This trial was registered at www.clinicaltrials.gov as #NCT01929408.

Maximising Capacity and Saving Cost in an Outpatient Chemotherapy Centre during a Pandemic: A Quality Improvement Project

Introduction Blood transfusion is an integral part of routine outpatient Haematology-Oncology care. Blood product administration requires the concerted effort of nursing and laboratory staff in accredited institutions. One of the challenges with scheduling transfusions is the unpredictability surrounding transfusion requirements and the amount of time required to administer blood products. This mismatch between capacity availability for ad hoc transfusions and clinical need has resulted in physicians pre-booking transfusion slots so patients can be transfused if needed. However, when patients do not require transfusions, their cancelled slots represent capacity which could have otherwise been used to administer chemotherapy. This problem is exacerbated in a pandemic, where demand for inpatient beds necessitates the transition of elective chemotherapy to the outpatient setting insofar as is possible. Aim We hypothesized that reducing the number of transfusion slots booked could help to save healthcare-related costs and improve capacity utilisation. We also sought to right-site blood transfusions away from the chemotherapy infusion unit and to an acute cancer care unit (ACCU). Methods On 1 May 2020, two simple workflow changes were made. First, we introduced a policy where transfusions could not be pre-booked. Physicians were reassured that their patients would be transfused before their patient's crossmatch sample expired and that urgent transfusions would be done on the same day. The only exceptions to this policy were regularly transfused patients (e.g. thalassaemia major patients on chronic transfusions) and infirm patients. Secondly, ad hoc blood transfusions were moved from the chemotherapy unit to the acute cancer care unit. Ad hoc transfusion timing was prioritised according to clinical need. Consecutive patients treated at the National University Cancer Institute, Singapore, from 1 July 2019 to 31 July 2020 were included. Scheduled appointments were extracted from the hospital's scheduling system and analysed. Patients who had appointments booked for blood product transfusions were included. Data was extracted from drug ordering systems to determine the number of blood products administered. Patients were divided into a historical control group (before 1 May) and a study group (after 1 May). The primary outcome measures were cancellation rate (defined as the number of cancellations over total number of slots booked for transfusion) and number of chair hours wasted. Secondary outcome measures included the number of patients who had to be admitted for blood transfusion due to lack of slot availability and cost savings reflected in unit chair hours made available. Categorical data were analysed by the chi-square test. Analysis was done with SPSS v22 (IBM, USA). Results Between 1 July 2019 and 31 July 2020, a total of 3144 slots were booked for transfusion. Each slot was booked for four hours. 1548 blood products were administered. In the control group, there were 1630 cancellations. This equated to 6520 hours of chemotherapy chair time (average of 652 hours/month). There were no nett cancellations in the study group, as total number transfused exceeded the number booked. Assuming the booking rate would have been similar without our intervention, the study resulted in 1956 unutilised chair hours saved. This reflects capacity created for administration of chemotherapy, and cost savings of 1956x, where x is the unit cost of one chair hour. The cancellation rate was 58.3% (1630 cancelled, 2800 booked) in the control group. This decreased to -9.9% in the study group (378 administered (i.e., no nett cancellations), 344 booked, p&amp;lt;0.001, Figure 1). No patients had to be admitted for elective blood transfusion after 1 May 2020. One patient had to be admitted emergently for blood transfusion because of concurrent cardiac failure. The primary reason for admission was intravenous diuresis. All ad hoc transfusions were administered in ACCU. Conclusion Efficient utilisation brought about by two simple workflow changes can help to create capacity and save costs. Such strategies are especially critical in a pandemic, where healthcare resources are under major strain and existing capacity must be maximised. Disclosures No relevant conflicts of interest to declare.

Intensive Care Unit Capacity, Cancellation of Elective Surgery, and the US Pandemic Response.

Intensive Care Unit Capacity, Cancellation of Elective Surgery, and the US Pandemic Response.

AML-145: Multicenter 11-Year Experience of Outcomes After Intensive Versus Less-Intensive Therapy for Patients with Acute Myeloid Leukemia: Focus on Older and Medically Infirm Patients

Context Acute myeloid leukemia (AML) has a median survival of 6-12 months, with no major improvement over the last two decades. AML is a disease of elderly patients. Less-intensive induction therapies increasingly used in older patients, presuming they are more effective/better tolerated than intensive therapies. Objective Compare survival, quality of life (QOL), and function between less-intensive versus intensive therapies. Design, Setting, and Patients We studied a retrospective cohort (n=1,295) treated from 2008-2012 at six institutions, followed by a prospective observational cohort (n=692) treated from 2013-2017 at thirteen institutions. Both cohorts were ages 18-80 years. Main outcome measures Survival estimates were obtained with the Kaplan-Meier method. We used an AML-composite model (AML-CM) assigning higher scores to increasing age, comorbidity burden, and adverse cytogenetics. Less- and more-intensive induction therapies were compared within distinct prognostic groups defined by AML-CM. We used a competing-risk Cox regression model to test the impact of allogeneic transplant (HCT). Prospective QOL and function were compared between less-intensive and intensive groups across time using logistic regression. Results 20% and 21% of patients received less-intensive therapies in the retrospective and prospective cohorts, respectively. In both cohorts, less-intensive therapies were used more often with increasing age, comorbidity burden, and cytogenetic/molecular risks, and also with Karnofsky Performance Status (KPS) ≤ 70%. Retrospective cohort patients with AML-CM scores of 4-6, 7-9, and ≥10, respectively, had significantly higher hazard ratios (HR) for death after less-intensive therapies, independent from receipt of HCT [in HCT-adjusted models, AML-CM=4-6: HR=1.82 (95% CI=1.25-2.63); =7-9: HR=1.67 (95% CI=1.22-2.27); >10: HR=1.32 (95% CI=0.99-1.72)]. Patients aged 70-79 years had similar results [HR=1.37 (95% CI=1.02-1.85), p=0.04]. Higher mortality risks were also seen in the prospective cohort after less-intensive therapies. In models adjusted for age, physician-assigned KPS and physician perceptions of chances of cure, mortality risks were similar between less-intensive and intensive therapies; QOL and function were also similar. Conclusions We did not find that receiving less-intensive induction led to better survival, QOL, or function compared to intensive therapies, including in those aged 70-79 years or with high comorbidity burden. This challenges current practice and demonstrates the need for a randomized trial. This research was, in part, funded by a Patient-Centered Outcome Research Institute award (CE-1304-7451), in part, by a Research Scholar Grant from the American Cancer Society (RSG-13-084-01-CPHPS), and, in part, supported by an American Society for Hematology Bridge Award.

Surgical Infection Society Guidance for Operative and Peri-Operative Care of Adult Patients Infected by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated viral infection (coronavirus disease 2019, COVID-19) is a virulent, contagious viral pandemic that is affecting populations worldwide. As with any airborne viral respiratory infection, surgical and non-surgical patients may be affected. Methods: Review and synthesis of pertinent English-language literature pertaining to COVID-19 infection among adult patients. Results: COVID-19 disease that requires hospitalization results in critical illness approximately 25% of the time and requires mechanical ventilation with positive airway pressure. Acute kidney injury, a marked hypercoagulable state, and sometimes myocarditis can be features of COVID-19 in addition to the characteristic severe acute lung injury. Even if not among the most seriously afflicted, older patients with medical comorbidities are both predisposed to infection and risk increased morbidity and mortality, however, all persons presenting for surgical intervention should be suspected of infection (and thus transmissibility) even if asymptomatic. Although most elective surgery has been curtailed by administrative or governmental fiat, patients will still need urgent or emergency operative intervention for time-sensitive disease processes such as malignant neoplasia or for true emergencies such as perforated viscus or traumatic injury. It is possible to provide safe surgical care for SARS-CoV-2-positive patients and minimize nosocomial transmission to healthcare workers. Conclusions: This guidance will facilitate appropriate protection of patients and staff, and maintenance of infection control measures to assist surgical personnel and facilities to prepare for COVID-19-infected adult patients requiring urgent or emergent operative intervention and to provide optimal patient care.

Treatment of Frail Older Adults and Elderly Patients With Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia: Results of a Prospective Trial With Minimal Chemotherapy

BackgroundThe treatment of acute lymphoblastic leukemia (ALL) in older adults and elderly patients is a challenge, and modern protocols include targeted therapy and immunotherapy in combination with attenuated or minimal chemotherapy. However, frail patients are excluded from these trials, and reports on the outcome of this subgroup of patients are scarce. Our objective was to analyze the outcome of unfit older adults and elderly patients with Philadelphia chromosome-negative ALL included in a prospective trial (ALL-07FRAIL). Patients and MethodsOlder adults and elderly patients with Charlson Comorbidity Index (CCI) ≥ 4 were included. Induction therapy consisted of vincristine and dexamethasone, and maintenance therapy with mercaptopurine and methotrexate for 2 years. ResultsSeventy-two patients with a median age of 67 years (range, 57-89 years) and a median CCI of 5 (range, 4-12) were included. The rates of early withdrawal, early death, resistance, and complete response (CR) were 5%, 10%, 31%, and 54%, respectively. Six patients with CR abandoned the study, 5 died in CR, and 23 relapsed (cumulative relapse incidence 75%). The medians of disease-free and overall survival (OS) were 6.9 months (95% confidence interval [CI], 0.3-13.5 months) and 7.6 months (95% CI, 6.3-8.9 months), respectively. The most frequent toxic events were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases). Eastern Cooperative Oncology Group score but not the CCI had significant impact on OS. ConclusionComplete remission with very attenuated chemotherapy can be attained in one-half of older or elderly infirm patients with ALL. These results suggest that some of these patients could benefit from the concomitant or subsequent use of immunotherapy and/or targeted therapy.

Identification of Prognostic Biomarkers in the Urinary Peptidome of the Small Renal Mass

Renal cell carcinoma (RCC) is often diagnosed incidentally as a small renal mass (SRM; pT1a, ≤4 cm). Increasing concerns surrounding the overtreatment of patients with benign or clinically silent SRMs has resulted in a recent shift in treatment recommendations, especially in elderly and infirm patients. There are currently no biomarkers that can predict progression. We used a quantitative label-free liquid chromatography-tandem mass spectrometry peptidomics approach and targeted parallel-reaction monitoring to identify early, noninvasive diagnostic and prognostic biomarkers for early-stage RCC-SRMs. In total, 115 urine samples, including 33 renal oncocytoma (≤4 cm) cases, 30 progressive and 26 nonprogressive clear cell RCC-SRM cases, and 26 healthy controls were evaluated. Nine endogenous peptides that displayed significantly elevated expression in clear cell RCC-SRMs relative to healthy controls were identified. Peptides NVINGGSHAGNKLAMQEF, VNVDEVGGEALGRL, and VVAGVANALAHKYH showed significantly elevated expression in clear cell RCC-SRMs relative to renal oncocytoma. Additionally, peptides SHTSDSDVPSGVTEVVVKL and IVDNNILFLGKVNRP displayed significantly elevated expression in progressive relative to nonprogressive clear cell RCC-SRMs. Peptide SHTSDSDVPSGVTEVVVKL showed the most significant discriminatory utility (area under the curve, 0.76; 95% CI, 0.62-0.90; P=0.0027). Patients with elevated SHTSDSDVPSGVTEVVVKL expression had significantly shorter overall survival (hazard ratio, 4.13; 95% CI, 1.09-15.65; P=0.024) compared to patients with low expression. Pretreatment characterization of urinary peptides can provide insight into early RCC progression and may aid clinical decision-making and improve disease management.

Prognostic urinary miRNAs for the assessment of small renal masses

BackgroundRenal cell carcinoma (RCC) is often detected incidentally as a small renal mass (SRM; pT1a, ≤4 cm). It is clinically challenging to predict progression in patients with SRMs. This is largely due to the recent recognition of clinically progressive and non-progressive RCC-SRMs. It is critical to accurately stratify SRM patients according to risk to avoid unnecessary treatment. This is especially significant for elderly and infirm patients, where the risk of surgery outweighs mortality from SRMs. MethodsWe employed a qRT-PCR array-based approach and targeted qRT-PCR to identify and validate early, non-invasive diagnostic and prognostic biomarkers of RCC-SRMs. In total, we evaluated eighty urine samples, including 30 renal oncocytoma (≤4 cm) cases, 26 progressive and 24 non-progressive clear cell RCC-SRM (ccRCC-SRM) cases. ResultsWe identified nine urinary miRNAs which displayed significantly elevated expression in ccRCC-SRMs (pT1a; ≤4 cm) relative to renal oncocytoma (≤4 cm). Additionally, miR-328-3p displayed significantly down-regulated expression in progressive relative to non-progressive ccRCC-SRMs. Patients with elevated miR-328-3p expression had significantly longer overall survival (HR = 0.29, 95% CI = 0.08–1.03, p = 0.042) compared to patients with low miR-328-3p expression. We also found no significant association between miR-328-3p expression levels and gender, age, laterality, tumor size, or grade, suggesting that miR-328-3p is an independent prognostic biomarker. ConclusionsOur in-depth miRNA profiling approach identified novel biomarkers for early-stage ccRCC-SRMs. Pretreatment characterization of urinary miRNAs may provide insight into early RCC progression and could potentially aid clinical decision-making, improving patient management and reducing overtreatment.

Allogeneic Hematopoietic Cell Transplantation in the Outpatient Setting.

Conditioning with fludarabine and low-dose total-body irradiation before allogeneic hematopoietic cell transplantation (HCT) enabled treating older or medically infirm patients with advanced hematologic malignancies in the outpatient setting. Between December 1997 and June 2017, 1037 patients with hematologic malignancies received peripheral blood stem cell (PBSC) grafts from HLA-matched or 1 HLA antigen/allele-mismatched related or unrelated donors. Median age was 58 (range, 18 to 80) years. Serious comorbidities with Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) scores ≥3 were present in 52% of patients. We found that 47% of patients were either never hospitalized or only had an overnight hospital stay for infusion of late-arriving PBSCs while 53% were admitted for a median of 6 days. Main reasons for admission were infection, fever, graft-versus-host disease, and regimen-related toxicity. Two thirds of admissions occurred within 3 weeks of HCT. The 5-year risk of nonrelapse mortality (NRM) was 26% among hospitalized patients and 13% among nonhospitalized patients. Significant risk factors for hospitalization included unrelated transplants, 1 HLA antigen-mismatched transplant, high HCT-CI scores, and diagnosis of nonmyeloma malignancies. Significant risk factors for NRM were hospitalization, older age, unrelated transplants, and high HCT-CI scores. Ambulatory allogeneic HCT is feasible and safe.