Compromised Performance Status Research Articles

How we treat octogenarians with brain metastases.

Biologically younger, fully independent octogenarians are able to tolerate most oncological treatments. Increasing frailty results in decreasing eligibility for certain treatments, e.g., chemotherapy and surgery. Most brain metastases are not an isolated problem, but part of widespread cancer dissemination, often in combination with compromised performance status. Multidisciplinary assessment is key in this vulnerable patient population where age, frailty, comorbidity and even moderate additional deficits from brain metastases or their treatment may result in immobilization, hospitalization, need for nursing home care, termination of systemic anticancer treatment etc. Here, we provide examples of successful treatment (surgery, radiosurgery, systemic therapy) and best supportive care, and comment on the limitations of prognostic scores, which often were developed in all-comers rather than octogenarians. Despite selection bias in retrospective studies, survival after radiosurgery was more encouraging than after whole-brain radiotherapy. Prospective research with focus on octogenarians is warranted to optimize outcomes.

Effects of Palliative Chemotherapy in Unresectable or Metastatic Colorectal Cancer Patients With Poor Performance Status

IntroductionColorectal cancer is the second most common cancer in both genders and often presents as a metastatic, unresectable, or recurrent disease in early follow-up. It is uncertain the benefit of oxaliplatin-based palliative chemotherapy (CT) in the first line of treatment in patients with compromised performance status (PS), Eastern Cooperative Oncology Group (ECOG) 3 and 4. These patients are systematically excluded from clinical trials but may be treated in clinical practice. MethodsWe conducted a prospective observational cohort whose primary outcome was improving at least 2 points in the worst symptom in the Edmonton Symptom Assessment System Scale (ESAS-r), without grade 3 to 4 toxicity, comparing baseline and fourth week of treatment. Secondary endpoints included quality of life using the European Quality of Life-5 dimensions questionnaire, toxicity, response rate, clinical improvement of ECOG PS, and overall survival (OS). ResultsWe included 28 patients, and 12 (42.8%) achieved the primary endpoint. Median overall survival was 86 days, 46% of patients did not respond to the fourth-week reevaluation due to clinical deterioration, and 17.8% presented toxicity grade ≥3, with 5 patients dying from toxicity. In addition, ECOG PS 4 or cholestasis had poorer overall survival. Finally, 25% and 53.6% of patients received these treatments in the last 14 and 30 days of life, respectively. ConclusionIn the present study, palliative multiagent chemotherapy in poor performance status patients with non-molecularly selected colorectal cancer tended to impact tumor symptoms control; however, there is no benefit in OS and a considerable risk of toxicity and treatment-related death.

First-line (1L) treatment patterns in advanced non-small cell lung cancer (NSCLC) patients (pts) who are elderly or have compromised performance status (PS).

e18783 Background: Previous studies demonstrated that pts > 80 years (80+), or compromised PS (ECOG PS > 2, PS 2+) are frequently not treated for advanced NSCLC, despite studies demonstrating survival benefit with active therapy. We hypothesized that new therapies (e.g., immunotherapy) have changed practice in these populations. Here, we present new subgroup analysis in pts 80+ or PS2+. Methods: We conducted a retrospective, observational cohort study using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database to describe 1L treatment patterns from 2011 to 2020 in pts with advanced NSCLC. Pts 80+ could only be included from 2015 as the database suppressed birth years prior to 1935 due to privacy protection. Pts were excluded if there was a > 90-day post-diagnosis gap in EHR data. Treatment groups included PD-1/PD-L1 inhibitor single agent, chemoimmunotherapy, platinum-based doublet +/- VEGF inhibitors (VEGFi), single agent chemotherapy and tyrosine kinase inhibitors (TKIs). Descriptive statistics were used to analyze treatment patterns by year, and the relationship between 1L treatments and variables of interest were tested using Cochran-Armitage trend tests. Results: Of 58,145 pts with advanced NSCLC in the database, 6,528 were 80+ (2015+) and 8,611 had PS2+ at diagnosis (2011+). While the proportion of pts who did not receive any documented treatment has decreased for those 80+ (p < 0.0001), the proportion remains the same in pts with PS2+ (p = 0.78; Table). There was rapid uptake of PD-1/PD-L1 inhibitors as well as chemoimmunotherapy upon FDA approvals in 2016 and 2018, respectively. This correlated with a rapid decrease in platinum-doublet chemotherapy +/- VEGFi and single agent chemotherapy use. Single agent immunotherapy was favored in pts 80+ (Table). TKIs accounted for 9-11% of treatment employed in pts 80+ and 6-8% in pts with PS2+, without notable change across the study period. Conclusions: Real world data from 2011 to 2020 demonstrates rapid incorporation of immunotherapy into 1L treatment for NSCLC pts who are 80+ or PS2+. A substantial proportion of pts in these subgroups (32.8% and 35.1%, respectively) still do not receive treatment. [Table: see text]

Can CDK 4/6 inhibitors be used in patients with visceral crises? Deviating from conventional teaching

Visceral crisis is a situation in which the vital organ function is impaired due to infiltration by cancer cells. It Is of particular importance in the subset of HR+/Her2- metastatic breast cancer.. Current guidelines that recommend cytotoxic chemotherapy for visceral crisis are based on historical data that indicate that chemotherapy has higher response rates than endocrine therapy. These trials included patients with advanced breast cancer who were not selected for the hormonal receptor or Her 2 receptor status. In addition, the comparator had a weak endocrine agent. Objective response rates with endocrine therapy in combination with any of the CDK 4/6 inhibitors in patients with measurable disease range from 50-59%. These response rates are higher than the chemotherapy rates found in the historical trials. Moreover, patients with visceral crisis have a compromised performance status and impaired organ functions. Therefore, it is unlikely that these patients would tolerate complete doses of the most active chemotherapeutic agents, including anthracycline and taxane. The retrospective analysis of the real-world data base clearly demonstrates that the combination of endocrine agents with a CDK 4/6 inhibitor is superior to chemotherapy with improvement in overall survival. In conclusion, it is time to redefine the guidelines and consider endocrine therapy with a CDK 4/6 combination as the preferred option in the initial management of the visceral crisis.

OA08.02 First Line Treatment Patterns in Advanced NSCLC Patients With Compromised Performance Status or Comorbidities

Non-small cell lung cancer (NSCLC) is a disease of the elderly and most cases are related to tobacco. Therefore, concomitant organ dysfunction (dfxn), which increases the risk of toxicity with cancer directed therapy, is prevalent. Patterns of care studies have shown that the elderly, those with organ dfxn or compromised performance status (PS) are frequently not treated, despite prospective studies demonstrating survival benefit with active treatment (tx). We hypothesized that the advent of new, more active therapies has resulted in practice changes in these populations.

Factors for Timely Identification of Possible Occurrence of Delirium in Palliative Care: A Prospective Observational Study.

Delirium occurs in 50–80% of end-of-life patients but is often misdiagnosed. Identification of clinical factors potentially associated with delirium onset can lead to a correct early diagnosis. To this aim, we conducted a prospective cohort study on patients from an Italian palliative care unit (PCU) admitted in 2018–2019. We evaluated the presence of several clinical factors at patient admission and compared their presence in patients who developed delirium and in those who did not develop it during follow-up. Among 503 enrolled patients, after a median follow-up time of 16 days (interquartile range 6–40 days), 95 (18.9%) developed delirium. Hazard ratios (HR) and corresponding 95% confidence intervals were computed using Cox proportional hazard models. In univariate analyses, factors significantly more frequent in patients with delirium were care in hospice, compromised performance status, kidney disease, fever, renal failure, hypoxia, dehydration, drowsiness, poor well-being, breathlessness, and “around the clock” therapy with psychoactive drugs, particularly haloperidol. In multivariate analyses, setting of care (HR 2.28 for hospice versus home care, 95% CI 1.45–3.60; p < 0.001), presence of breathlessness (HR 1.71, 95% CI 1.03–2.83, p = 0.037), and administration of psychoactive drugs, particularly haloperidol (HR 2.17 for haloperidol, 95% CI 1.11–4.22 and 1.53 for other drugs, 95% CI 0.94–2.48; p = 0.048) were significantly associated with the risk of developing delirium. The study indicates that some clinical factors are associated with the probability of delirium onset. Their evaluation in PC patients could help healthcare professionals to identify the development of delirium in those patients in a timely manner.

Analysis of first-line treatment (tx) patterns in advanced non-small cell lung cancer (NSCLC) patients (pts) with compromised performance status (PS), organ dysfunction (dfxn) or other significant comorbidities.

e21093 Background: NSCLC is a disease of the elderly and most cases are related to tobacco. Therefore, concomitant organ dfxn, which increases the risk of toxicity with cancer directed therapy, is prevalent. Patterns of care studies have shown that the elderly, those with organ dfxn or compromised PS are frequently not treated, despite prospective studies demonstrating survival benefit with active tx. We hypothesized that the advent of new, more active therapies has resulted in practice changes in these populations. Methods: We conducted a retrospective, observational cohort study using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database to compare first line tx patterns from 2011 to 2020 in pts with advanced NSCLC meeting at least 1 of the following criteria: age &gt; 70 years, organ dfxn (serum creatinine &gt; 1.5 times the upper limit of normal [ULN] and/or total bilirubin &gt; 2 times ULN), ECOG PS &gt; 2 or documented HIV. Pts were excluded if there was a &gt; 90-day post-diagnosis gap in EHR data. Tx patterns were categorized as having received standard, non-standard or no frontline tx. Tx groups included PD-1/PD-L1 inhibitor single agent, chemoimmunotherapy, platinum-based (Plat) doublet +/- VEGF inhibitors (VEGFi), single agent chemotherapy (chemo) and tyrosine kinase inhibitors (TKIs). Descriptive statistics were used to analyze tx patterns, and the relationship between txs and variables of interest were tested using Chi-squared tests or t-tests. Results: Of the 58,145 pts with advanced NSCLC in the database, 33,701 met at least 1 criterion for inclusion. There was a small but significant increase in the number of pts treated with standard therapy from 2011 to 2020 (p &lt; 0.001). There was rapid uptake of PD-1/PD-L1 inhibitors as well as chemoimmunotherapy upon FDA approvals in 2016 and 2018, respectively. This correlated with a rapid decrease in the use of Plat-doublet chemo +/- VEGFi as well as a decrease in the number of pts receiving single agent chemo or not treated at all (Table). Conclusions: Real world data from 2011 to 2020 demonstrates an increase in the use of standard therapies as well as the rapid incorporation of immunotherapy into first line tx in advanced NSCLC pts who are elderly, have a poor PS, or organ dfxn. However, a substantial proportion of pts (28.9%) still do not receive any documented tx, within the Flatiron Health network.[Table: see text]

Challenges of HIV Lymphoma Clinical Trials in Africa: Lessons From the AIDS Malignancy Consortium 068 Study.

The purpose of this article is to describe lessons from the first lymphoma clinical trial conducted by the AIDS Malignancy Consortium (AMC) in sub-Saharan Africa (SSA). AMC-068 was a randomized phase II comparison of intravenous versus oral chemotherapy for HIV-positive diffuse large B-cell lymphoma. Opening in 2016, AMC-068 planned to enroll 90 patients (45 per arm) in Kenya, Malawi, Uganda, and Zimbabwe over 24 months and follow patients for 24 months to assess overall survival. In 2018, the study closed after screening 42 patients but enrolling only 7. Challenges occurred during protocol development, pre-activation, and postactivation. During protocol development (2011-2012), major obstacles were limited baseline data to inform study design; lack of consensus among investigators and approving bodies regarding appropriateness of the oral regimen and need for randomized comparison with cyclophosphamide, doxorubicin, vincristine, and prednisone; and heterogeneity across sites in local standards for diagnosis, staging, and treatment. During pre-activation (2012-2016), challenges included unexpected length and layers of regulatory approval across multiple countries, need to upgrade pathology capacity at sites, need to augment existing chemotherapy infusion capacity at sites, and procurement issues for drugs and supplies. Finally, during postactivation (2016-2018), challenges included long delays between symptom onset and screening entry for many patients, leading to compromised performance status and organ function; other patient characteristics that frequently led to exclusion, including high tumor proliferative index or other pathologic features that were disallowed; and costs of routine diagnostic procedures often being borne by patients, which also contributed to pre-enrollment delays. Lessons from AMC-068 are being applied to the design and conduct of new AMC lymphoma trials in SSA, and the study has contributed to a strong operational foundation that will support innovative clinical trials in the future.

Protocolo fisioterapêutico aplicado no pós-operatório imediato para recuperação acelerada de pacientes submetidos à procedimentos cirúrgicos torácicos no Hospital Santa Marcelina – Itaquera (PROSM): estudo clínico randomizado

INTRODUÇÃO: A cirurgia torácica pode causar uma série de complicações pulmonares após o processo cirúrgico. O momento e a circunstância ideais para sedestação fora do leito e suas implicações clínicas, após cirurgias no tórax, ainda necessitam de padronização. Assim, faz-se necessário um tratamento de mobilização precoce adequado visando minimizar as complicações no período pós-operatório. OBJETIVOS: Objetivamos avaliar o efeito do atendimento fisioterapêutico no pós-operatório imediato de pacientes submetidos à cirurgia torácica. MATERIAIS E MÉTODOS: Este será um ensaio clínico randomizado, no qual um grupo de pacientes submetidos às cirurgias de ressecções pulmonares eletivas (segmentectomias, lobectomias ou pneumonectomias) com idade superior a dezoito anos receberão atendimento fisioterapêutico através do PROSM. Serão excluídos os pacientes incapazes de assinar o termo de consentimento livre esclarecido, com performance status comprometido (ECOG superior à 2), com peso corporal inferior à 60 Kg ou superior à 120 Kg, com alergia a qualquer uma das drogas utilizadas na anestesia, portadores de disfunção renal, disfunção hepática (Child B e C) e Insuficiência Cardíaca (classe Funcional III e IV). O instrumento de classificação do grau da dor por meio da Escala Visual Analógica (EVA) e instrumento de classificação da independência funcional por meio da Escala MIF (medida de independência funcional) serão aplicados antes do início e após o término de cada sessão de fisioterapia. Também será analisado o número de sessões de cada paciente e o tempo de internação. Para análise estatística será utilizado o programa SPSS Statistics e o teste de Shapiro-Wilk será usado para identificar a normalidade dos dados coletados. Espera-se um menor tempo de internação e melhor independência funcional na alta hospitalar nos pacientes submetidos ao PROSM.

Ceritinib in anaplastic lymphoma kinase-positive nonsmall cell lung cancer among patients who were previously exposed to crizotinib: Experience from the Indian subcontinent.

Ceritinib is a novel ALK inhibitor approved for advanced stage NSCLC with ALK gene rearrangement, progressed and/or intolerant to crizotinib. 13 patients were included in our study who received ceritinib. Majority of them were women and never smokers with a median age of 47 yrs. Nearly half of them had a compromised performance status and received ceritinib in third line and beyond. Ceritinib showed nearly 50% response rates. With a median follow up of 9 months for the entire cohort, median PFS and OS were not reached. However, the mean values for PFS and OS were 10.9 and 14.8 months,with an estimated 1 year PFS and OS being 56% and 78% respectively.1/3 of the patients had gastrointestinal and liver toxicities. Metabolic abnormalities were seen in 1/4 th of them. ceritinib was permanently discontinued in one patient due to pneumonitis. In conclusion, ceritinib has a favorable efficacy and side effect profile in our patient population., similar to that reported in large clinical trials. It has shown promising efficacy even in patients with compromised performance status; presence of brain metastases and heavily pre-treated disease.

ROS1 rearranged nonsmall cell lung cancer and crizotinib: An Indian experience.

ROS1 rearrangement acts as a driver mutation in 1-2% of NSCLC. Crizotinib is approved in this situation both in treatment naïve and pre-treated patients. Here we report our experience with crizotinib in patients with advanced NSCLC harbouring ROS1 rearrangement. Eleven patients were included in our study. More than half of our patients had associated comorbidities and one fourth of them had a compromised performance status. Out of 11 patients, 5 of them were exposed to crizotinib .The response rates among crizotinib treated patients was 80%. With a median follow up of 9 months, median PFS and OS were 5.4 months and 8.5 months respectively for the entire population. Analyzing the outcomes separately , median PFS and OS was not reached for those who received crizotinib compared to median PFS of 2.5 months and median OS of 4.2 months in those who were not exposed to crizotinib. The difference was statistically significant. Estimated 1 year OS was 80% for those who received crizotinib compared to 18% for who did not receive crizotinib. In conclusion, crizotinib is effective with acceptable side effect profile in patients with ROS1 rearranged NSCLC in our population.

Outcomes of Autologous Transplantation for Treatment-Related AML and MDS in Previously Treated Multiple Myeloma Patients (pts)

Introduction:Therapy related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) are significant long-term complications of MM treatment. We have treated pts on standard therapy protocols including TT2, TT3, TT4 and TT5. These protocols include an induction, tandem melphalan-based ASCT and consolidation, followed by three years of maintenance. As a part of the protocols, multiple bone marrow examinations including metaphase cytogenetics are performed at regular intervals, giving us the unique opportunity to examine the development of t-MDS/t-AML and understand the efficacy of subsequent treatment. Here we investigate the outcome of t-AML and t-MDS treated with autologous stem cell transplantation (ASCT) in MM patients.Materials and Methods, Results:During the period between 1998 to 2015, a total of 1558 pts were treated for MM with standard therapy protocols. We identified 68 pts out of 1558 who developed t-AML + t-MDS. Thirty-one had a confirmed diagnosis of t-AML, and thirty-seven had a diagnosis of t-MDS. The median age at diagnosis was 60 years (range 45-76). The median time from diagnosis MM of t-AML and t-MDS was 66 months (range, 9.6-155.4) and 63 months (range, 8-130), respectively. Baseline cytogenetics were as follows: complex cytogenetics in 34 pts out of 68, del(7) in 24 pts, del(5) in 17 pts, and del(17p) in 5 pts.Eighteen out of thirty-one t-AML pts were treated with ASCT. The remaining 13 pts did not receive ASCT. The treatment related mortality (TRM) at day100 (D100) in the ASCT group was 33% (6/18 pts). Neutrophil and platelet engraftment was achieved in all 18 pts by D21. Complete remission was achieved in 50% (9 out of 18) of pts. When we compared pts who received ASCT to those who were treated with chemotherapy only, the median overall survival (OS) was 11.28 months after ASCT vs 1.32 months without ASCT (p < 0.05). Nineteen out of thirty seven t-MDS pts were treated with ASCT. When we compared pts who received ASCT to chemotherapy only for t-MDS, there was no difference in survival between the groups. A mortality rate of 47% (9/19) was recorded at D200 after transplantation due to severe infections and lack of engraftment.Conclusion:t-AML and t-MDS treatment is a significant therapeutic challenge for the elderly, who often have poor risk cytogenetic markers, significant comorbidities and a compromised performance status. In our case series of post MM therapy t-AML, ASCT prolonged survival. In contrast, there was no change in survival of t-MDS pts, most likely due to high rate of infectious complications seen in this group. To our knowledge, this is the first analysis suggesting a survival benefit from ASCT in treating t-AML. Although the numbers in our study are small, we recommend that ASCT can be safely considered for t-AML patients who are physically fit, have autologous stem cells in storage and are overseen by a good supportive care team. These results need to be validated in large prospective studies. DisclosuresAtrash:University of Arkansas for Medical Sciences: Employment. Barlogie:Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; European School of Haematology- International Conference on Multiple Myeloma: Other: Travel Stipend; ComtecMed- World Congress on Controversies in Hematology: Other: Travel Stipend; International Workshop on Waldenström's Macroglobulinemia: Other: Travel Stipend; Dana Farber Cancer Institute: Other: Travel Stipend; Multiple Myeloma Research Foundation: Other: Travel Stipend; Myeloma Health, LLC: Patents & Royalties: Co-inventor of patents and patent applications related to use of GEP in cancer medicine licensed to Myeloma Health, LLC. Zangari:Onyx: Research Funding; Novartis: Research Funding; Millennium: Research Funding; University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Waheed:University of Arkansas for Medical Sciences: Employment. Bailey:University of Arkansas for Medical Sciences: Employment. Petty:University of Arkansas for Medical Sciences: Employment. Heuck:Celgene: Consultancy; Janssen: Other: Advisory Board; Millenium: Other: Advisory Board; Foundation Medicine: Honoraria; University of Arkansas for Medical Sciences: Employment. Morgan:Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; MMRF: Honoraria; Weismann Institute: Honoraria; CancerNet: Honoraria; University of Arkansas for Medical Sciences: Employment; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Jethava:University of Arkansas for Medical Sciences: Employment.

Bacillus amyloliquefaciens supplementation alleviates immunological stress in lipopolysaccharide-challenged broilers at early age

This study was conducted to investigate the effect of Bacillus amyloliquefaciens (BA) on the immune function of broilers challenged with lipopolysaccharide (LPS). 192 one-day-old male Arbor Acre broiler chickens were randomly distributed into four treatments: 1) broilers fed a basal diet; 2) broilers fed a basal diet supplemented with BA; 3) LPS-challenged broilers fed a basal diet; and 4) LPS-challenged broilers fed a basal diet supplemented with BA. Each treatment consisted of six replicates with eight broilers per replicate. Broilers were intraperitoneally injected with either 500 μg LPS per kg body weight or sterile saline at 16, 18 and 20 d of age. LPS decreased the average daily gain (ADG, P = 0.001) and average daily feed intake (P = 0.001). The decreased ADG (P = 0.009) and increased feed conversion ratio (P = 0.047) in LPS-challenged broilers were alleviated by BA. LPS increased the relative spleen weight (P = 0.001). Relative spleen (P = 0.014) and bursa (P = 0.024) weights in the LPS-challenged broilers were reduced by BA. LPS increased white blood cell (WBC) numbers (P = 0.001). However, the WBC numbers (P = 0.042) and the ratio of lymphocytes to WBC (P = 0.020) in LPS-challenged broilers were decreased with BA treatment. LPS decreased plasma lysozyme activity (P = 0.001), but increased concentrations of plasma corticosterone (P = 0.012) and IL-2 (P = 0.020). In contrast, BA increased lysozyme activity in plasma (P = 0.040). LPS increased mRNA abundances of splenic toll-like receptor 4 (P = 0.046), interferon γ (P = 0.008), IL- 1β (P = 0.045) and IL-6, (P = 0.006). IL-2 (P = 0.014) and IL-6 (P = 0.074) mRNA abundances in LPS-challenged broilers were reduced by BA, although BA had an opposite effect for IL-10 mRNA expression in those broilers (P = 0.004). In conclusion, BA supplementation could partially alleviate the compromised growth performance and immune status of broilers under immune stress induced by LPS challenge at early age.

Impact of comorbidity on prognosis in patients with small cell lung cancer: A retrospective analysis.

e18556 Background: Patients (pts) with small cell lung cancer (SCLC) often suffer from relevant comorbidity. In addition, they frequently present with a compromised performance status (PS). Outside...

To transplant or not: a dilemma for treatment of elderly AML patients in the twenty-first century

AML treatment presents significant challenges in the elderly, who more often have poor risk cytogenetic and molecular markers, comorbidities and compromised performance status. Although population-based studies indicate that treated patients' survival is better than those who are not treated, there is an understandable reluctance of physicians to choose aggressive therapy. Even in this older population 40-60% CR rates are achievable. Several scoring systems and web-based programs help to predict TRM and CR rates. These sources can assist physicians in the difficult decision-making process of aggressive therapy in an individual patient. Clofarabine and hypomethylating agents are reasonable options and can induce CR in patients who cannot receive standard induction with anthracyclines and cytarabine. Despite encouraging CR rates, median survival remains short (<12 months) in elderly AML patients. Even those patients achieving CR have limited long-term survival (∼20% at 3 years) without allogeneic hematopoietic cell transplantation (alloHCT). AlloHCT is feasible and can provide approximately 40% survival at 2 years in appropriately selected patients. Although increased age is associated with poorer survival, higher comorbidities and poor performance status have more negative impact than age per se. The short duration of CR demands that leukemia and transplant physicians collaborate immediately after diagnosis to move quickly toward alloHCT. This collaboration is also essential to choosing the right individuals to transplant and to bridging post-remission therapy (intermediate-dose cytarabine, a hypomethylating agent or FLT-3 inhibitor) in this sometimes frail population. Future studies should be designed not only to address who should receive alloHCT, but also to improve our understanding of AML biology and the process of its cure.

Selection of mode of biopsy in histopathological diagnosis of Soft tissue sarcoma depending on diagnostic accuracy and feasibility: Debatable issue in modern era

Background: Biopsy method of choice is a controversy issue for diagnosis of soft tissue sarcoma which are traditionally been managed by wide excision surgery and radiotherapy. Chemotherapy is reserved for advanced cases. Aims & Objective: The objective of study was to evaluate diagnostic accuracy of various modes of biopsy focusing on image guided core needle biopsy (CNB). Material and Methods: Current study includes 50 cases of soft tissue sarcoma from January 2010 to October 2012. The Mode of biopsies included image guided CNB, open and excision biopsy. Effective accuracy of each was determined by accuracy of biopsy to provide adequate tissue for histopathological and other special examinations like immunohistochemistry to reach final diagnosis. Results: Out of total 50 cases CNB was done in 13 cases, open biopsy in 2 cases and in 35 cases excision biopsy was done. CNB was adequate in 92.31 % cases and 7.69 % cases it was inadequate. Open and excision biopsy were 100 % adequate. Conclusion: Image guided CNB is very helpful in early diagnosis and shows high accuracy especially for high-grade sarcoma. It is less invasive compared to others and differentiate benign from malignant. It is handful when preoperative diagnosis is essential for planning pre-operative chemotherapy especially in patients with primarily inoperable, advanced tumour with compromised performance status or recurrent tumour. But it should be properly directed and representative of whole tumour and require full radiological correlation by experienced hands. Tumours with myxoid pattern, lipomatous tumours and low grade sarcomas encounters lower diagnostic accuracy on CNB.

Comparison of Outcomes After Related and Unrelated Hematopoietic Cell Transplantation in Adults with Myelodysplastic Syndromes: A Report From the Center for International Blood and Marrow Transplant Research (CIBMTR)

AbstractAbstract ▪355▪This icon denotes a clinically relevant abstractApproximately one-third of patients considered for hematopoietic cell transplantation (HCT) have human leukocyte antigen (HLA) matched related donors (MRD). HLA-matched unrelated donor (MUD) HCT is an alternative approach for the others. A prior CIBMTR analysis showed that transplantation from MUD and MRD donors produces similar survival for patients with acute myelogenous leukemia (AML) (Blood 2012; 119(17):3908–16). Patients with myelodysplastic syndromes (MDS) often are older and have more compromised performance status than patients with AML. There are also differences in disease biology and pre-transplant therapies between the disorders that could lead to different outcomes. Therefore, a disease-specific analysis of post-HCT outcomes after MUD vs. MRD was performed. Outcomes of 701 adult MDS patients who underwent allogeneic HCT between 2002 and 2006 were analyzed (MRD, n=176; 8/8 HLA-A, B, C, DRB1 allele matched MUD, n=413; 7/8 MUD, n=112). Median age was 53 years (range, 22–78). Thirty-one percent had Karnofsky performance scores (KPS) <90% at HCT. Sixty-five percent had advanced disease and 19% had therapy-related MDS. Seventy-seven percent received peripheral blood stem cells; 40% received reduced intensity conditioning regimens. The 100-day cumulative incidence of grades B-D (IBMTR Index) acute graft-versus-host disease (GVHD) was significantly lower in MRD HCT recipients than in 8/8 MUD and 7/8 MUD HCT recipients (42%, 54%, and 57%, respectively; p=0.009). The corresponding 3-year cumulative incidences of chronic GVHD were similar among the three groups (51%, 49%, and 41%; p=0.25). In multivariate analyses, 8/8 MUD HCT recipients had similar DFS and survival rates compared to MRD HCT recipients (relative risk [RR] 1.11 (95% confidence intervals [CI] 0.89–1.39) and 1.24 (95% CI 0.98–1.56), respectively); 7/8 MUD HCT recipients had inferior DFS (RR 1.43, 95% CI 1.08–1.91) and survival (1.62, 95% CI 1.21–2.17) when compared to MRD HCT recipients and when compared to 8/8 MUD HCT recipients (RR 1.29, 95% CI 1.00–1.65 for DFS and 1.30, 95% CI 1.01–1.68 for survival) (Tables 1, 2 and Figure). Differences in outcome were largely related to excess TRM; relapse was not significantly different among the three groups (overall p value=0.33) (Tables 1 and 2). In patients with MDS, transplantation from 8/8 MUD and MRD donors produces similar survival, however, 7/8 MUD HCT is associated with inferior outcomes.Table 1Adjusted 3-Year Cumulative Incidences of TRM, Relapse, and 3-Year Probabilities of DFS and Survival in Adult MDS Patients who Underwent HLA-Identical Sibling (MRD) HCT or 8/8 or 7/8 Matched Unrelated Donor (MUD) HCT from 2002–2006*MRD Probability (95% CI)8/8 MUD Probability (95% CI)7/8 MUD Probability (95% CI)8/8 MUD vs. MRD P value‡7/8 MUD vs. MRD P value‡7/8 MUD vs. 8/8 MUD P value‡TRM30 (24-37)41 (36-46)42 (33-51)0.010.030.77Relapse32 (25-39)24 (20-28)27 (19-35)0.0580.300.59DFS40 (33-47)35 (30-40)29 (21-37)0.220.040.19Survival47 (40-55)38 (34-43)31 (22-39)0.040.0030.11*Adjusting for patient-related (age, gender, KPS), disease-related (International Prognostic Scoring System stage at diagnosis (d-IPSS), white blood cell count at diagnosis, therapy-related MDS, and disease status at HCT), and HCT-related variables (time between diagnosis and HCT, donor-recipient CMV and gender match, graft type, conditioning and GVHD prophylaxis regimens).‡Pointwise pairwise comparison.Table 2Multivariate Analysis for TRM, Relapse, Treatment Failure (Inverse of DFS), and Mortality in Adult MDS Patients who Underwent HLA-Identical Sibling (MRD) HCT or 8/8 or 7/8 Matched Unrelated Donor (MUD) HCT from 2002–2006*TRM# RR (95 % CI)P valueRelapse± RR (95 % CI)P valueTreatment Failure (Death or Relapse)‡ RR (95 % CI)P valueMortality∥ RR (95% CI)P value8/8 MUD vs. MRD1.37 (1.01-1.85)0.030.78 (0.55-1.10)0.161.11 (0.89-1.39)0.331.24 (0.98-1.56)0.067/8 MUD vs. MRD1.71 (1.17-2.47)0.0040.94 (0.60-1.47)0.791.43 (1.08-1.91)0.011.62 (1.21-2.17)0.0017/8 MUD vs. 8/8 MUD1.24 (0.90-1.70)0.171.20 (0.80-1.79)0.371.29 (1.00-1.65)0.041.30 (1.01-1.68)0.03Other Significant factors also include:*See Table 1 for variables adjusted for in the analysis.#KPS and female donor into male recipient.±Disease status at HCT, d-IPSS, and conditioning regimen.‡KPS and d-IPSS.∥Age, KPS, and d-IPSS. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Impact of neutropenia on the outcomes of critically ill patients with cancer: a matched case–control study

BackgroundThe prognostic effect of neutropenia in cancer patients admitted to intensive care units (ICUs) was addressed exclusively in cohort studies with conflicting results. Our aim was to address this question using a matched case–control study. Patients and methodsNinety-four neutropenic patients and 94 non-neutropenic controls were matched for age, cancer type, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment score, and need for mechanical ventilation and vasopressors. Conditional logistic regression was used to identify factors associated with hospital mortality. ResultsThe ICU (66% versus 66%, P=0.999) and hospital (73% versus 78%, P=0.611) mortality rates were similar in neutropenic and non-neutropenic patients. Adjusting for the type of admission and length of hospital stay before ICU admission, the characteristics associated with increased mortality were the severity of acute disease and organ failures, compromised performance status and sepsis diagnosis. The impact of both previous chemotherapy and neutropenia on the outcomes was not significant. ConclusionsUsing a matched case–control study design, our results provide additional evidence that the presence of neutropenia is no longer associated with worse outcomes in critically ill patients with cancer. Moreover, our results also corroborate that recent exposure to chemotherapy is not associated with increased risk for death.

Critically ill patients with cancer and sepsis: Clinical course and prognostic factors

PurposeThe purposes of this study were to evaluate the clinical course and to identify independent predictors of mortality in patients with cancer with sepsis. Materials and MethodsThis is a secondary analysis of a prospective cohort study conducted at an oncological medical-surgical intensive care unit. Logistic regression was used to identify predictors of hospital mortality. ResultsA total of 563 patients (77% solid tumor, 23% hematologic malignancies) were included over a 55-month period. The most frequent sites of infection were the lung, abdomen, and urinary tract; 91% patients had severe sepsis/septic shock. Gram-negative bacteria were responsible for more than half of the episodes of infection; 38% of patients had polymicrobial infections. Intensive care unit, hospital, and 6-month mortality rates were 51%, 65%, and 72%, respectively. In multivariate analyses, sepsis in the context of medical complications; active disease; compromised performance status; presence of 3 to 4 systemic inflammatory response syndrome criteria; and the presence of respiratory, renal, and cardiovascular failures were associated with increased mortality. Adjusting for other covariates, patients with non–urinary tract infections, mostly represented by patients with pneumonia and abdominal infections, had worse outcomes. ConclusionsSepsis remains a frequent complication in patients with cancer and associated with high mortality. Our results can be of help to assist intensivists in clinical decisions and to improve characterization and risk stratification in these patients.

Maintaining Bone Health in Patients With Multiple Myeloma

About 90% of individuals with multiple myeloma will develop osteolytic bone lesions from increased osteoclastic and decreased osteoblastic activity. Severe morbidities from pathologic fractures and other skeletal events can lead to poor circulation, blood clots, muscle wasting, compromised performance status, and overall poor survival. Supportive care targeting bone disease is an essential adjunct to antimyeloma therapy. In addition, the maintenance of bone health in patients with multiple myeloma can significantly improve quality of life. Oncology nurses and other healthcare providers play a central role in the management of bone disease and maintenance throughout the course of treatment. Safe administration of bisphosphonates, promotion of exercise, maintenance of adequate nutrition, vitamin and mineral supplementation, scheduled radiographic examinations, and monitoring of bone complications are among the important functions that oncology nurses and healthcare providers perform in clinical practice.