Impaired Performance Status Research Articles

An oncologic emergency case of massive dedifferentiated liposarcoma of the small bowel mesentery

We report the case of a 71-year-old man who complained of abdominal distension, pedal edema, respiratory discomfort, and weight gain. Computed tomography revealed a giant, poorly enhancing tumor occupying the entire abdomen, with abdominal ascites. The tumor was causing hydronephrosis, compression of the inferior vena cava, and elevation of the diaphragm. The patient exhibited deterioration of performance status (PS3 on the ECOG scale) and required oxygen; therefore, emergency surgery was performed. Operative findings included bloody abdominal ascites and peritoneal dissemination. The large tumor arose from the small bowel mesentery, and infiltrated into the cecum and sigmoid colon. Tumor excision with ileocecal resection and sigmoidectomy was performed. Histopathological examination revealed dedifferentiated liposarcoma. The patient was discharged on postoperative day 22, but pre-discharge CT revealed a recurrent liposarcoma in the retroperitoneum. Therefore, chemotherapy was initiated and the treatment has been continued for over 6months after surgery. Due to the rarity of this disease, there is no consensus regarding treatment strategies for DDLPS with peritoneal dissemination or in patients with a poor general condition, especially in the setting of oncologic emergency. In this case, multimodal treatment was used to successfully manage this life-threatening state and obtain satisfactory therapeutic results.

Palliative Treatment of Locally Advanced Non Metastatic Lung Cancer

Introduction: To determine the proportion and the reasons which lead to palliative treatment in patients initially a candidate for concomitant chemoradiotherapy (CCRT). Methods: A retrospective study including patients followed for locally advanced lung cancer newly diagnosed from April 1, 2016, to 12/31/2017 in the radiotherapy department of the National Oncology Institute who received palliative treatment. Results: We collected 52 patients out of a total of 225 stage III patients (23%) followed by lung cancer candidates for CCRT who had undergone palliative treatment. The mean age in our series was 61.23 years [22 - 81] with 86% male. The majority of patients (71%) had Performance Status (PS) ≤ 2. Histological confirmation was obtained by pathological examination in all our patients. It was an adenocarcinoma (ADK) in 54% of cases; squamous cell carcinoma in 46% of cases. The reasons for palliative treatment were mainly due to dosimetric constraints: large tumor volume 22/52 (42%); the tumor location close to the bone marrow in 15 of 52 (29%) patients; and general Performance Status impairment (29%) in 15 of 52 patients. Palliative treatment consisted of palliative chemotherapy in 37 of 52 patients (71%), among whom 19 (51%) were stable after 2 months of chemotherapy, in palliative dose chest radiotherapy on the pulmonary parenchyma and/or mediastinum in 10 of 52 (19%) patients, and supportive care in 5 (10 %) patients. We observed 40/52 (77%) cases of stationary course, 04/52 (8%) cases of progress to metastases, and 08/52 (15%) deaths before radiotherapy. Conclusion: A large proportion of patients followed for locally advanced non-metastatic lung cancer are not eligible for curative treatment. The reasons for the palliative treatment of patients followed for lung cancer candidates for CCRT are variable but for a large proportion of patients due to the deterioration of their state of health during their diagnostic journey. Hence, there is the need to improve the early diagnosis and early management of patients with lung cancer to avoid delayed care.

Pre-treatment optimization with pulmonary rehabilitation in lung cancer: Making the inoperable patients operable.

BackgroundAnatomical lung resection offers the best prospect of long-term survival in patients with non-small cell lung cancer (NSCLC). However, some patients with significant dyspnoea, impaired performance status (PS), borderline or poor pulmonary function are considered inoperable and instead referred for radiotherapy, chemotherapy or palliative care. The aims of the study were to determine whether pre-operative pulmonary physiotherapy (Prehab), by improving clinical parameters, (i) makes patients suitable for surgery who were considered inoperable on subjective criteria of dyspnoea >3 and PS >2, and objective criteria of diffusing capacity for carbon monoxide (DLCO) <50%; and (ii) thereby allows them to safely receive curative surgery with reduced morbidity and mortality.MethodsFrom January 2017 to December 2018 a total of 306 patients were prospectively and sequentially assessed for Prehab and 216 patients with lung cancer studied. Their mean age (95% CI) was 71.7 ± 1.1 years, 50.5% (n = 109) were men and they received Prehab over 39.0 ± 7.0 days averaging 3.1 ± 0.6 sessions. Their dyspnoea scores, PS, level of activity, six minute walk test (6MWT) and frailty index prior to and following Prehab were determined. Following surgery the post-operative length of hospital stay (LOHS), complications and mortality at 30 days, 90 days and 1 year determined. Similar outcomes were determined for (i) high-risk patients with dyspnoea scores >3 and PS >2, and compared with low-risk patients having dyspnoea scores <2 and PS <2 (subjective criteria); and (ii) high-risk patients with DLCO <50% and compared with low-risk patients with DLCO >80% (objective criteria).FindingsIn the total cohort following Prehab, there was significant improvement in the dyspnoea scores <2 / ≥2 (40%/60% prior to Prehab vs. 65%/35% following Prehab, p = 0.00002), PS <2 / ≥2 (45%/55% prior to vs. 62%/38% following Prehab, p = 0.003), frailty index ≤3 / >3 (49%/51% vs 70%/30%, p = 0.0006), and 6MWT (306.6 ± 6.8 m vs 354.8 ± 52.7 m, p = 0.04). Post-operative major complication rates were 8.7%; median LOHS was 7 (IQR 6) days; hospital mortality at 30 days 1.3%, 90 days 4.7% and 1 year 16%. Using subjective criteria of dyspnoea scores >3 and PS >2, 100% of high-risk patients were considered inoperable. Following optimization with Prehab 84.2% of the high-risk patients were ready to proceed with radical treatment and 52.6% with surgery, and subsequently 42.8% of patients underwent surgery. Likewise, 78.8% of patients with DLCO <50% were considered inoperable. Following Prehab 86.5% of high-risk patients were ready to proceed with radical treatment and 59.1% with surgery, and 54.6% of high-risk patients underwent surgery. In each category there were no significant differences in complications, LOHS or mortality rates between the high-risk and low-risk patients.InterpretationOur prospective study showed that with Prehab there was clinical and statistically significant improvement in the dyspnoea scores, PS, level of activity and frailty, particularly in the high-risk group of patients. Importantly, Prehab made previously inoperable patients operable, allowing them to safely undergo curative lung resection. This strategy helps improve resection rates and may contribute to the long term survival of lung cancer patients.FundingThis is a Welsh Health Specialised Services Committee (WHSSC) commissioned service.

Characterisation of 22445 patients attending UK emergency departments with suspected COVID-19 infection: Observational cohort study.

Hospital emergency departments play a crucial role in the initial assessment and management of suspected COVID-19 infection. This needs to be guided by studies of people presenting with suspected COVID-19, including those admitted and discharged, and those who do not ultimately have COVID-19 confirmed. We aimed to characterise patients attending emergency departments with suspected COVID-19, including subgroups based on sex, ethnicity and COVID-19 test results. We undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22445 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. Outcomes were admission to hospital, COVID-19 result, organ support (respiratory, cardiovascular or renal), and death, by record review at 30 days. Mean age was 58.4 years, 11200 (50.4%) were female and 11034 (49.6%) male. Adults (age >16 years) were acutely unwell (median NEWS2 score of 4), frequently had limited performance status (46.9%) and had high rates of admission (67.1%), COVID-19 positivity (31.2%), organ support (9.8%) and death (15.5%). Children had much lower rates of admission (27.4%), COVID-19 positivity (1.2%), organ support (1.4%) and death (0.3%). Similar numbers of men and women presented to the ED, but men were more likely to be admitted (72.9% v 61.4%), require organ support (12.2% v 7.7%) and die (18.2% v 13.0%). Black or Asian adults tended to be younger than White adults (median age 54, 50 and 67 years), were less likely to have impaired performance status (43.1%, 26.8% and 51.6%), be admitted to hospital (60.8%, 57.3%, 69.6%) or die (11.6%, 11.2%, 16.4%), but were more likely to require organ support (15.9%, 14.3%, 8.9%) or have a positive COVID-19 test (40.8%, 42.1%, 30.0%). Adults admitted with suspected and confirmed COVID-19 had similar age, performance status and comorbidities (except chronic lung disease) to those who did not have COVID-19 confirmed, but were much more likely to need organ support (22.2% v 8.9%) or die (32.1% v 15.5%). Important differences exist between patient groups presenting to the emergency department with suspected COVID-19. Adults and children differ markedly and require different approaches to emergency triage. Admission and adverse outcome rates among adults suggest that policies to avoid unnecessary ED attendance achieved their aim. Subsequent COVID-19 confirmation confers a worse prognosis and greater need for organ support. ISRCTN registry, ISRCTN56149622, http://www.isrctn.com/ISRCTN28342533.

QOLP-23. PHASE II RANDOMISED PLACEBO-CONTROLLED DOUBLE-BLIND STUDY OF ACETAZOLAMIDE VERSUS PLACEBO FOR CEREBRAL OEDEMA IN RECURRENT AND/OR PROGRESSIVE HIGH-GRADE GLIOMA REQUIRING TREATMENT WITH DEXAMETHASONE

Abstract INTRODUCTION Symptoms of raised intracranial pressure (ICP) in recurrent or progressive high-grade glioma (HGG) generally require corticosteroid treatment, often causing toxicity with variable effects on reversing ICP symptoms. Acetazolamide reduces ICP in other clinical settings including case series in glioma. AIM To explore whether addition of oral acetazolamide enables safe dexamethasone dose reduction in management of raised ICP in recurrent and/or progressive HGG. METHODS Participants had recurrent, progressive and/or persistent residual HGG requiring recommencement of dexamethasone, dose increase or dexamethasone dependency; prior/current bevacizumab was an exclusion. Eligible participants were randomised 1:1 to acetazolamide 250mg twice daily or placebo for 8 weeks. Standardised protocols were used for dexamethasone dose changes in both arms, with planned dose decrease from day 5 once ICP symptoms were stable. The primary endpoint was a composite of dexamethasone dose reduction and stability of performance status. Secondary endpoints included toxicity and feasibility (accrual and compliance). RESULTS Thirty participants of a planned sample of 84 were enrolled (mean age 58 y (32-89)) from 7 Australian sites. The mean baseline dexamethasone dose was 6.2mg (4-16mg). Mean duration on treatment was 38 days (4-57) in placebo group and 31 days (3-60) in acetazolamide group, with 9 participants (30%) completing all study treatment (6 placebo, 3 acetazolamide). Study withdrawal was due to adverse events (n=6 (1 placebo, 5 acetazolamide)) and disease progression (n=6 (3 per arm)). Four participants (13%) (2 per arm) were stable responders meeting the primary endpoint criteria (≥50% corticosteroid dose reduction from baseline by 28 days maintained for 7 days, and no deterioration in performance status). Ten participants experienced a total of 13 serious adverse events (acetazolamide arm: 5 participants (33%), 6 events, 2 related). DISCUSSION The addition of acetazolamide did not facilitate dexamethasone reduction. The study closed early due to poor accrual and increasing availability of bevacizumab.

Impact of musculoskeletal degradation on cancer outcomes and strategies for management in clinical practice.

The prevalence of malnutrition in patients with cancer is one of the highest of all patient groups. Weight loss (WL) is a frequent manifestation of malnutrition in cancer and several large-scale studies have reported that involuntary WL affects 50-80% of patients with cancer, with the degree of WL dependent on tumour site, type and stage of disease. The study of body composition in oncology using computed tomography has unearthed the importance of both low muscle mass (sarcopenia) and low muscle attenuation as important prognostic indications of unfavourable outcomes including poorer tolerance to chemotherapy; significant deterioration in performance status and quality of life (QoL), poorer post-operative outcomes and shortened survival. While often hidden by excess fat and high BMI, muscle abnormalities are highly prevalent in patients with cancer (ranging from 10 to 90%). Early screening to identify individuals with sarcopenia and decreased muscle quality would allow for earlier multimodal interventions to attenuate adverse body compositional changes. Multimodal therapies (combining nutritional counselling, exercise and anti-inflammatory drugs) are currently the focus of randomised trials to examine if this approach can provide a sufficient stimulus to prevent or slow the cascade of tissue wasting and if this then impacts on outcomes in a positive manner. This review will focus on the aetiology of musculoskeletal degradation in cancer; the impact of sarcopenia on chemotherapy tolerance, post-operative complications, QoL and survival; and outline current strategies for attenuation of muscle loss in clinical practice.

We report performance status in oncology—but not nutritional status?

Performance status (PS) scales are used routinely in clinical oncology to evaluate functional status and help direct treatment decisions. PS is also used to determine research protocol eligibility, indicate treatment response, and evaluate toxicity in oncology clinical trials. Malnutrition (like poor PS) is associated with adverse outcomes such as lower tolerance to anti-tumor treatment, poor quality of life, and decreased survival. Nutritional status is therefore arguably as important as PS for cancer outcomes. Despite well-documented adverse consequences for patients, malnutrition also often goes undiagnosed until severe depletion is evident. If the predictive importance of nutritional status is comparable to PS, why is nutritional status not routinely used along with PS to guide treatment decisions? There is compelling evidence to support the predictive abilities of both PS and nutritional status in cancer outcomes and treatment decision-making. Perhaps, PS may be a proxy for nutritional status. Nutritional status might also serve as an effective tool for patient selection and stratification in oncology trials. Together with PS, it might provide important and distinct prognostic information; we propose both should be routinely included in outcome studies. The extent to which impaired PS may be a surrogate for malnutrition warrants investigation. Given its comparable importance to PS, it is inexcusable that nutritional status is not given the prominence it deserves as a key patient-reported outcome.

1651P Pegylated liposomal doxorubicin as first line treatment in patients with advanced soft tissue sarcoma: A single-center retrospective study

Pegylated liposomal doxorubicin (PLD) is associated with equivalent efficacy, less cardiotoxicity and better toxicity profile than free doxorubicin; however, we have limited knowledge and experience in patients (Pts) with soft tissue sarcoma (STS). We retrospectively collected data (approved by ethics committee) on STS Pts treated with PLD (50 mg/m2 d1, q4w) from 2012 to 2018 at our institution. Inclusion criteria: Non-resectable or metastatic disease, first line treatment, non-rhabdomyosarcoma, complete medical record, ECOG 0-3. 34 pts were included. Female 62%, median age 52.5 (24-80), ECOG 0-1: 67%, ECOG 2-3: 33%. Leiomyosarcoma 35%, liposarcoma 17%, fibrosarcoma 9%, Undifferentiated pleomorphic sarcoma 9%, synovial 9%, other 21%. Primary site: Pelvic/abdominal 47%, extremities 41%, H&N 6%. Metastases: lung 56%, liver 35%, non-resectable retroperitoneal tumor 47%. Median number of cycles 3 (1-8). Progression Free Survival (PFS): 3 months, PFS 6 months: 32%. Overall Survival (OS) 10 months, OS 1 year: 38%. Pts ECOG ≤1: PFS 3.6 months, OS 13 months. Pts ECOG ≥2: PFS 1.4 months, OS 2.1 months. CR 6.9%, PR 13.8%, SD 34.4%, PG 44.9%, ORR 20.7%, CBR 55%. Subgroup analysis OS: ECOG HR 4.1 (CI 1.62-10.41; P=0.003), retroperitoneal disease HR 6.95 (CI 1.44-33.52; P=0.016). Toxicity: G1/4 asthenia 66.9%, mucositis 44%, anaemia 38.3%, Neutropenia 29.4%, palmar-plantar erythrodysesthesia 20.6%, Infusion related reactions 2.9%, reduction LVEF >10% 2.9%, treatment death associated 0%. Toxicity G3/4: Neutropenia 14.7%, asthenia 8.8%, mucositis 2.9%, anaemia 2.9%. ECOG 0-1 Toxicity G3/4: 8.3%. ECOG 2-3 Toxicity G3-4: 45.5%. PLD is an active drug in Pts with advanced STS and good performance status (PS). The results of the study indicate no benefit in PFS or OS and high toxicity in Pts with ECOG 2-3. Clinical trial or best supportive care remains the preferred treatment for pts with impaired PS.

Role of Multimodal Treatment in Urothelial Carcinoma Spinal Metastasis: 15 Patients' Experiences in a Single Center.

PurposeSpinal metastasis from urothelial carcinoma (UC) is relatively uncommon. The aim of the present study is to explore the clinicopathological features, surgical treatments and outcomes of this rare disease.Patients and MethodsFifteen patients with UC spinal metastasis who received surgery in our center between 2009 and 2018 were retrospectively investigated. Clinical data, treatment options, and outcomes were analyzed.ResultsFor the 15 patients (9 men and 6 women), the primary tumors were located in the upper urothelial tract in ten and lower urothelial tract in five. UC mainly metastasized to the lumbar spine in seven cases, followed by the thoracic spine in five. Pathologic fracture and soft tissue mass with dura mater compression were observed in 66.7% and 93.3% cases, respectively. Palliative resection was performed in nine cases and excisional resection in six. Eleven patients received postoperative chemotherapy, including three with a preoperative ECOG score >2. Bisphosphonates were administered in all patients. Pain was relieved remarkably in all patients, and both the neurological function and general status were improved significantly after surgery. The median overall survival was 14 months. Log rank test showed that patients receiving postoperative chemotherapy survived longer than those without chemotherapy (p=0.037). WHO grade 3 was also correlated with poorer prognosis (p=0.012).ConclusionPathological fracture and soft tissue mass with dura mater compression is frequently observed on radiological images in patients with UC spinal metastasis. Surgery is useful to prevent deterioration of performance status and improve quality of life, which provide an opportunity for further systematic therapy. Multimodal treatments, including surgery, postoperative chemotherapy and bisphosphonates are recommended. WHO grade 2 and receiving postoperative chemotherapy were favorable prognostic factors for the overall survival of patients with UC spinal metastasis.

Elderly patients with cancer admitted to intensive care unit: A multicenter study in a middle-income country.

Very elderly critically ill patients (ie, those older than 75 or 80 years) are an increasing population in intensive care units. However, patients with cancer have encompassed only a minority in epidemiological studies of very old critically-ill patients. We aimed to describe clinical characteristics and identify factors associated with hospital mortality in a cohort of patients aged 80 or older with cancer admitted to intensive care units (ICUs). This was a retrospective cohort study in 94 ICUs in Brazil. We included patients aged 80 years or older with active cancer who had an unplanned admission. We performed a mixed effect logistic regression model to identify variables independently associated with hospital mortality. Of 4604 included patients, 1807 (39.2%) died in hospital. Solid metastatic (OR = 2.46; CI 95%, 2.01-3.00), hematological cancer (OR = 2.32; CI 95%, 1.75-3.09), moderate/severe performance status impairment (OR = 1.59; CI 95%, 1.33-1.90) and use of vasopressors (OR = 4.74; CI 95%, 3.88-5.79), mechanical ventilation (OR = 1.54; CI 95%, 1.25-1.89) and renal replacement (OR = 1.81; CI 95%, 1.29-2.55) therapy were independently associated with increased hospital mortality. Emergency surgical admissions were associated with lower mortality compared to medical admissions (OR = 0.71; CI 95%, 0.52-0.96). Hospital mortality rate in very elderly critically ill patients with cancer with unplanned ICU admissions are lower than expected a priori. Cancer characteristics, performance status impairment and acute organ dysfunctions are associated with increased mortality.

Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma

CD19-targeted chimeric antigen receptor (CAR) T cell therapy is an effective treatment for diffuse large B cell lymphoma (DLBCL). In addition to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), B cell aplasia and hypogammaglobulinemia are common toxicities predisposing these patients to infections. We analyzed 60 patients with DLBCL treated with FDA-approved CD19 CAR T cells and report the incidence, risk factors, and management of infections during the first year after treatment. A total of 101 infectious events were observed, including 25 mild, 51 moderate, 23 severe, 1 life-threatening, and 1 fatal infection. Bacteria were the most common causative pathogens. The cumulative incidence of overall, bacterial, severe bacterial, viral, and fungal infection at 1 year were 63.3%, 57.2%, 29.6%, 44.7%, and 4%, respectively. In multivariate analyses, the use of systemic corticosteroids for the management of CRS or ICANS was associated with an increased risk of infections and prolonged admission. Impaired performance status and history of infections within 30 days before CAR T cell therapy was a risk factor for severe bacterial infection. In conclusion, infections were common within the first 60 days after CAR T cell therapy, however, they were not associated with an increased risk of death.

Real world aspects of palliative trifluridine plus tiperacil (TAS-102) in refractory metastatic colorectal cancer.

While recent randomised phase III trials show that trifluridine/tiperacil (TAS-102) may prolong life in patients with refractory metastatic colorectal cancer (rmCRC), palliative aspects on its efficacy and tolerability in real world patients need further elucidation. A retrospective observational multicentre study was designed, including all patients with rmCRC who received TAS-102 under 2016-2019 in the South East Health Care region of Sweden. 48 patients were identified. Primary outcome was overall survival (OS) and secondary outcomes were progression-free survival (PFS), time to ECOG performance status deterioration (PSD), safety and dose reductions, admission to and duration of access to palliative care, and administration of TAS-102 in the last 30 days before death. Median OS, PFS, and time to PSD (a proxy for impaired quality of life) from start of TAS-102 were 6.4 months (95% CI: 4.4-8.4), 2.3 months (95% CI: 1.8-2.7) and 2.5 months (95% CI: 1.9-3.2), respectively. Following uni- and multivariable regression analyses, the number of previous treatment lines (≤2 vs. ≥3) was statistically independent for OS (median 7.8 vs. 5.3 months, P=0.05), PFS (median 2.4 vs. 1.8 months, P=0.03), and time to PSD (median 2.8 vs. 1.8 months, P=0.03). Thirty-four (71%) of the patients received reduced doses. The most common grade 3-4 toxicity was neutropenia (39%). Forty-three (90%) were admitted to GP or hospital-based home palliative care. Median time for access to any form of palliative care before death was 2.3 (95% CI: 0.5-3.2) months. Few patients (n=3, 7%) received their last dose of TAS-102 in their last 30 days of life. The outcome and tolerability of TAS-102 in rmCRC appear similar in a real-world context and randomised trials. The retrospective design and limited sample size preclude firm conclusions on subgroup analyses, but it appears that the prognosis is slightly better the earlier TAS-102 is introduced. Treatment durations are generally short, and early admission to a palliative care provider is recommended.

Incidence and preoperative predictors for major complications following radical nephroureterectomy.

BackgroundRadical nephroureterectomy (RNU) is the referent standard for managing bulky, invasive, or high grade upper-tract urothelial carcinoma (UTUC). The UTUC patient population, however, generally harbor medical comorbidities thereby placing them at risk of surgical complications. This study reviews a large international cohort of RNU patients to define the risk of major complications and preoperative factors associated with their occurrence.MethodsPatients undergoing RNU at 14 academic medical centers between 2002 and 2015 were retrospectively reviewed. Preoperative clinical, demographic, operative, and comorbidity indices were recorded. The modified Clavien-Dindo index was used to grade complications occurring within 30 days of surgery. The association between preoperative variables and major complications occurring after RNU was determined by multivariable logistic regression.ResultsOne thousand two hundred and sixty-six patients (707 men; 559 women) with a median age of 70 years and BMI of 27 kg/m2 were included. Over three-quarters of the cohort was white, 50.1% had baseline chronic kidney disease (CKD) ≥ stage III, 22.4% had a Charlson comorbidity index (CCI) score >5, and 17.1% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2. Overall, 413 (32.6%) experienced a complication including 103 (8.1%) with a major event. Specific distribution of major complications included 49 Clavien III, 44 Clavien IV, and 10 Clavien V. On univariate analysis, patient age (P=0.006), hypertension (P=0.002), diabetes mellitus (P=0.023), CKD stage (P<0.001), American Society of Anesthesiologists (ASA) score (P=0.022), ECOG (P<0.001), and CCI (P<0.001) all were associated with major complications. On multivariate analysis, ECOG ≥2 (OR 2.38, 95% CI, 1.46–3.90), P=0.001), CCI >5 (OR 3.45, 95% CI, 1.41–8.33, P=0.007), and CKD stage ≥3 (OR 3.64, P=0.008) were independently associated with major complications.ConclusionsMajor complications following RNU occurred in almost 10% of patients. Impaired preoperative performance status and baseline CKD are preoperative variables associated with these major post-surgical adverse event. These easily measurable indices warrant consideration and discussion prior to proceeding with RNU.

DLBCL patients treated with CD19 CAR T cells experience a high burden of organ toxicities but low nonrelapse mortality

AbstractCytokine release syndrome (CRS) immune effector cell–associated neurotoxicity syndrome are the most notable toxicities of CD19 chimeric antigen receptor (CAR) T-cell therapy. In addition, CAR T-cell–mediated toxicities can involve any organ system, with varied impacts on outcomes, depending on patient factors and involved organs. We performed detailed analysis of organ-specific toxicities and their association with outcomes in 60 patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 CAR T cells by assessing all toxicities in organ-based groups during the first year posttreatment. We observed 539 grade ≥2 and 289 grade ≥3 toxicities. Common grade ≥3 toxicities included hematological, metabolic, infectious, and neurological complications, with corresponding 1-year cumulative incidence of 57.7%, 54.8%, 35.4%, and 18.3%, respectively. Patients with impaired performance status had a higher risk of grade ≥3 metabolic complications, whereas elevated lactate dehydrogenase was associated with higher risks of grade ≥3 neurological and pulmonary toxicities. CRS was associated with higher incidence of grade ≥3 metabolic, pulmonary, and neurologic complications. The 1-year nonrelapse mortality and overall survival were 1.7% and 69%, respectively. Only grade ≥3 pulmonary toxicities were associated with an increased mortality risk. In summary, toxicity burdens after CD19 CAR T-cell therapy were high and varied by organ systems. Most toxicities were manageable and were rarely associated with mortality. Our study emphasizes the importance of toxicity assessment, which could serve as a benchmark for further research to reduce symptom burdens and improve tolerability in patients treated with CAR T cells.

PD-7 Updated survival analysis of the Danish randomized study comparing trifluridine/tipiracil with or without bevacizumab in patients with chemo-refractory metastatic colorectal cancer

Our investigator-initiated randomized trial in patients with chemorefractory metastatic colorectal cancer (mCRC) patients demonstrated improved PFS and OS in patients receiving bevacizumab combined with trifluridine/tipiracil (FTD/TPI) as compared with patients treated with FTD/TPI alone (Pfeiffer et al, Lancet Oncol 2020). In the present study, we have updated PFS and OS per February 1st, 2020. Furthermore, will evaluate markers for no benefit (1 month CT scan and increase in CEA), look for time to deterioration of performance status, and details regarding treatment-related hospitalization.

Systematic symptom and problem assessment at admission to the palliative care ward \u2013 perspectives and prognostic impacts

BackgroundSymptom assessment is essential in palliative care, but holds challenges concerning implementation and relevance. This study aims to evaluate patients’ main symptoms and problems at admission to a specialist inpatient palliative care (SIPC) ward using physician proxy- and patient self-assessment, and aims to identify their prognostic impact as well as the agreement between both assessments.MethodsWithin 12 h after admission, palliative care specialists completed the Symptom and Problem Checklist of the German Hospice and Palliative Care Evaluation (HOPE-SP-CL). Patients either used the new version of the minimal documentation system for patients in palliative care (MIDOS) or the Integrated Palliative Care Outcome Scale (IPOS) plus the Distress Thermometer (DT).ResultsBetween 01.01.2016–30.09.2018, 1206 patients were included (HOPE-SP-CL 98%; MIDOS 21%, IPOS 34%, DT 27%) whereof 59% died on the ward. Proxy-assessment showed a mean HOPE-SP-CL Total Score of 24.6 ± 5.9 of 45. Most frequent symptoms/problems of at least moderate intensity were weakness (95%), needs of assistance with activities of daily living (88%), overburdening of family caregivers (83%), and tiredness (75%). Factor analysis identified four symptom clusters (SCs): (1) Deteriorated Physical Condition/Decompensation of Home Care, (2) Emotional Problems, (3) Gastrointestinal Symptoms and (4) Other Symptoms. Self-assessment showed a mean MIDOS Total Score of 11.3 ± 5.3 of 30, a mean IPOS Total Score of 32.0 ± 9.0 of 68, and a mean distress of 6.6 ± 2.5 of 10. Agreement of self- and proxy-assessment was moderate for pain (ƙ = 0.438) and dyspnea (ƙ = 0.503), fair for other physical (ƙ = 0.297 to 0.394) and poor for psychological symptoms (ƙ = 0.101 to 0.202). Multivariate regression analyses for single symptoms and SCs revealed that predictors for dying on the SIPC ward included impaired ECOG performance status, moderate/severe dyspnea, appetite loss, tiredness, disorientation/confusion, and the SC Deteriorated Physical Condition/Decompensation of Home Care.ConclusionAdmissions to a SIPC ward are mainly caused by problems impairing mobility and autonomy. Results demonstrate that implementation of self- and reliability of proxy- and self-assessment is challenging, especially concerning non-physical symptoms/problems. We identified, specific symptoms and problems that might provide information needed for treatment discussions regarding the medical prognosis.

Geriatric assessment (GA) predictors of 1y mortality in older adults with gastrointestinal (GI) malignancies: Results from the CARE study.

12047 Background: Chronologic age is an imperfect predictor of morbidity and mortality in older patients with newly-diagnosed GI malignancies. Identifying patients with GI malignancies that are at increased risk of mortality within the 1st year remains challenging given no prior studies have focused on this population, yet is critical to developing personalized treatment plans. To fill this gap, we examined predictors of 1y mortality using variables from a patient-reported GA in a prospective cohort of older adults with GI malignancies. Methods: Cancer and Aging Resilience Evaluation (CARE) is a prospective registry of older adults (≥60y) with cancer seen at UAB (J Geri Onc 2019; PMID 31005648). Patients with GI malignancies with GA completed within the timeframe of 3 mo. before and up to 6 mo. after diagnosis were included. Vital status (up to 12/7/2019) was ascertained by linking participants to LexisNexis. Multivariable Cox regression analysis was used to estimate associations between GA variables and 1y mortality, adjusting for age at cancer diagnosis, race, cancer stage (IV vs. I-III), cancer group (high risk: pancreatic, hepatobiliary, esophageal vs. low risk: colorectal, GIST, neuroendocrine, etc.), and planned chemotherapy (yes/no). Results: A total of 356 participants met eligibility criteria. Mean age at enrollment was 70y; 56.4% were females; 25% black; 47.1% had high-risk cancers. In unadjusted analysis, high-risk cancers, cancer stage, malnutrition, impaired performance status, limitations in social activities, impaired instrumental activities of daily living (IADL), physical health, mental health, anxiety, and ≥3 comorbidities were associated with higher 1y mortality. Our base model (demographic and clinical variables) demonstrated good discrimination (c statistic 0.758), but was improved with the addition of all significant GA variables (c-statistic 0.810). Fatigue and malnutrition were identified as the strongest predictors among the GA variables, and a model adding those to the base model retained high discrimination (c-statistic 0.804). The estimated 1yr survival was 53.1% for those with both fatigue and malnutrition compared to 88.1% in those with neither. Conclusions: Among older adults with GI malignancies, malnutrition and fatigue were the strongest GA predictors of 1yr mortality after adjusting for age and clinical factors. These findings provide evidence for developing targeted interventions in older patients with newly-diagnosed GI malignancies to reduce 1y mortality.

Performance status and end-of-life care among adults with non-small cell lung cancer receiving immune checkpoint inhibitors.

Adults with impaired performance status (PS) often receive immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) despite limited efficacy data and unknown effects on end-of-life care. This was a retrospective, single-site study of 237 patients with advanced NSCLC who initiated ICI treatment from 2015 to 2017. Cox regression was used to compare the overall survival (OS) of patients who had impaired PS (≥2) at the start of ICI treatment with those who had PS 0 or 1 using Cox regression. Logistic regression was conducted to analyze the association between ICI use in the last 30days of life and the use of end-of-life health care. The patient mean age at ICI initiation was 67years (range, 37-91years), and 35.4% of patients had PS ≥2. Most patients (80.8%) received ICI as second-line or later therapy. The median OS was 4.5months in patients with PS ≥2 and 14.3months in those with PS 0 or 1 (hazard ratio, 2.5; P<.0001). Among the patients who died (n=184), 28.8% who had PS ≥2 received ICIs in their last 30days of life compared with 10.8% of those who had PS 0 or 1 (P=.002). Receipt of ICI in the last 30days of life was associated with decreased hospice referral (odds ratio, 0.29; P=.008) and increased in-hospital deaths (odds ratio, 6.8; P=.001), independent of PS. Adults with advanced NSCLC and impaired PS experience significantly shorter survival after ICItreatment and receive ICIs near death more often than those with better PS. Receipt of anICI near death was associated with lower hospice use and an increased risk of death in the hospital. These results underscore the need for high-quality communication about potential tradeoffs of ICIs, particularly among adults receiving ICIs as second-line or later therapy.

Handgrip weakness, low fat-free mass, and overall survival in non-small cell lung cancer treated with curative-intent radiotherapy.

BackgroundAssessment of handgrip strength and fat‐free mass provides quick and objective information on muscle performance and mass that might complement subjective World Health Organization Performance Status (WHO PS). We investigated to what extent the presence of pre‐treatment handgrip weakness and low fat‐free mass index (FFMI) provides additional prognostic information on top of well‐established prognostic factors (including WHO PS) in non‐small cell lung cancer (NSCLC) patients selected for curative‐intent (chemo)radiation.MethodsProspectively, patients with early and locally advanced NSCLC (stages I‐III) treated with (chemo)radiation were enrolled. Handgrip weakness and low FFMI, derived from bioelectrical impedance analysis, were defined using normative values and were correlated with overall survival (OS).ResultsWe included 936 patients (age 68 ± 10 years; 64% male; 19% stage I, 9% stage II, and 72% stage III disease; 26% handgrip weakness; 27% low FFMI). In patients with good performance status (WHO PS 0 or 1), handgrip weakness and low FFMI were significant prognostic factors for OS, after adjustment for age, gender, disease stage, and co‐morbidities. The combined presence of handgrip weakness and low FFMI was a strong prognostic factor for OS when compared with patients with normal handgrip strength and FFMI (hazard ratio: 1.79, 95% confidence interval: 1.34–2.40, P < 0.0001). In patients with impaired performance status (WHO PS ≥ 2, 19% of sample), handgrip weakness and low FFMI were not related to OS.ConclusionsIn early and locally advanced NSCLC patients treated with curative‐intent (chemo)radiation who have good WHO PS, patients with combined handgrip weakness and low FFMI have the worst prognosis.

Prognosis of EGFR-mutant Lung Adenocarcinoma Patients With Malignant Pleural Effusion Receiving First-line EGFR-TKI Therapy Without Pleurodesis: A Single-institute Retrospective Study.

The survival benefit of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy without pleurodesis in EGFR-mutant lung adenocarcinoma patients with malignant pleural effusions (MPE) remains unclear. We retrospectively evaluated overall survival (OS) among EGFR wild-type lung adenocarcinoma patients with MPE who received chemotherapy with pleurodesis (CT+PLD) and without pleurodesis (CT-PLD), and EGFR-mutant lung adenocarcinoma patients with MPE who received EGFR-TKI therapy with pleurodesis (TKI+PLD) and without pleurodesis (TKI-PLD). There was no difference in OS between the CT+PLD and the CT-PLD groups (10.8 months vs. 7.4 months). As compared to the TKI+PLD group, OS tended to be longer in the TKI-PLD group (21.8 months vs. 31.1 months). Patients in the TKI-PLD group had no hypoalbuminemia or deterioration of performance status during management of MPE and could receive second- and further-line therapy. EGFR-mutant patients with MPE who received first-line EGFR-TKI therapy without pleurodesis may show a better prognosis than those with pleurodesis.