The Impact of Graft CD3+ T-Cell Dose on the Outcome of T-Cell Replete Human Leukocyte Antigen-Mismatched Allogeneic Hematopoietic Peripheral Blood Stem Cells Transplantation.

Background: Data on whether the graft CD3-positive (CD3+) T-cell dose in T-cell-replete human leukocyte antigen (HLA)-mismatched allogeneic hematopoietic peripheral blood stem cells transplantation (PBSCT) influences post-transplant outcomes are controversial. Methods: Using King Hussein Cancer Center (KHCC) Blood and Marrow Transplantation (BMT) Registry database, 52 adult subjects, receiving the first T-cell-replete HLA-mismatched allogeneic hematopoietic PBSCT for acute leukemias or myelodysplastic syndrome, were identified, from January 2017 to December 2020. The cutoff value of graft CD3+ T-cell dose was identified using the receiver operating characteristic (ROC) formula and Youden's analysis. Subjects were divided into two cohorts: cohort 1 with low CD3+ T-cell dose (n = 34) and cohort 2 with high CD3+ T-cell dose (n = 18). Correlative analyses were performed between CD3+ T-cell dose and the risk of graft-versus-host disease (GvHD), relapse, relapse-free survival (RFS), and overall survival (OS). P-values were two-sided and considered significant when P < 0.05. Results: Subject covariates were displayed. Subject's characteristics were comparable, except for higher nucleated cells and more female donors in the high CD3+ T-cell cohort. The 100-day cumulative incidence of acute GvHD (aGvHD) was 45±7% and 3-year cumulative incidence of chronic GvHD (cGvHD) was 28±6.7%. There was no statistically significant difference between the two cohorts in aGvHD (50% vs. 39%, P = 0.4) or cGvHD (29% vs. 22%, P = 0.7). The 2-year cumulative incidence of relapse (CIR) was 67.5±16.3% for low compared with 14.3±6.8% for high CD3+ T-cell cohort (P = 0.018). Fifteen subjects relapsed and 24 have died, 13 due to disease relapse. There was an improvement in 2-year RFS (94% vs. 83%; P = 0.0022) and 2-year OS (91% vs. 89%; P = 0.025) in low CD3+ T-cell cohort compared with high CD3+ T-cell cohort. Graft CD3+ T-cell dose is the only significant risk factor for relapse (P = 002), and OS (P = 0.030) in univariate analysis which was maintained in multivariate for relapse (P = 0.003), but not for OS (P = 0.050). Conclusions: Our data suggest that high graft CD3+ T-cell dose is associated with lower risk of relapse, and might improve long-term survival, but has no influence on the risk of developing aGvHD or cGvHD.

Validation of the Arabic Version of the Edmonton Symptom Assessment System.

Quality cancer care is a team effort. In addition, patients' symptoms change over the course of treatment. As such, the Edmonton Symptom Assessment System (ESAS) is a simple tool designed to quickly monitor symptom change. Here, we present the results from a two-phase study aimed at validating the Arabic version of the ESAS (ESAS-A). Phase one involved the creation of two versions of the ESAS with both reverse and forward translations by bilingual, native Arabic speakers as well as evaluation by an expert panel. The reconciled version was then administered to 20 patients as a pilot from which to create the final version, which was then used with 244 patients. Phase two for the ESAS-involved an ESAS-based validation of 244 adults aged 18 years and older who were diagnosed with advanced cancer; then, further validation was completed in conjunction with two other symptom survey tools, the EORTC-Pal 15 and the HADS. The ESAS-A items possessed good internal consistency with an average Cronbach's alpha of 0.84, ranging from 0.82 to 0.85. Moreover, the results of ESAS-A showed good agreement with those of EORTC QLQ- 15 PAL (r = 0.36 to 0.69) and HADS (r = 0.60 and 0.57) regarding anxiety and depression. We found the ESAS-A to be responsive to symptom change and a median time to completion of 3.73 min. The results of our study demonstrate that the ESAS-A is a reliable, valid, and feasible tool for the purposes of monitoring symptom change over the course of cancer treatment.

Impact of head-and-neck radiation oncology clinical fellowship on multidisciplinary assessment, radiation workflow, and survival of adult patients with nasopharyngeal carcinoma.

Purpose: The purpose of the study wast to evaluate the influence of head-and-neck clinical fellowship training on multidisciplinary assessment, radiation workflow, and clinical outcomes of patients with nasopharyngeal carcinoma (NPC). Materials and Methods: This was a retrospective review of patients with NPC treated between 2010 and 2017. The study cohort was allocated into prefellowship cohort (pre-FSC) (January 2010-September 2014) and postfellowship cohort (post-FSC) (October 2014-December 2017). Patient demographics, tumor characteristics, multidisciplinary assessment, radiation workflow, and treatment were reviewed. Univariable, multivariable, and relapse-free survival (RFS) and overall survival (OS) were performed. Results: One hundred and forty-three patients were included, 68 in the pre-FSC and 75 in the post-FSC. For the post-FSC versus pre-FSC, there were increased multidisciplinary referrals to dental (100% vs. 79.4%, P = 0.001), nutritional (94.7% vs. 70.6%, P = 0.0001), peg-tube insertion (84% vs. 64.7%, P = 0.0001), speech and swallow (94.7% vs. 13.2%, P = 0.0001), psychosocial (100% vs. 26.5%, P = 0.0001), and smoking cessation clinic (33.3% vs. 5.9%, P = 0.0001). For the post-FSC versus pre-FSC, there were statistically significant differences in the elements of radiation workflow; mean time required for contouring was 3.2 vs. 8.8 days (P = 0.0001), radiotherapy plan implementation: 1.9 vs. 4.8 days (P = 0.0001), and plan approval: 0.4 vs. 0.9 day (P = 0.00012). On multivariable analysis, smoking was associated with poor RFS (P = 0.04). There were no statistically significant differences in OS (94.7% vs. 87.2% at 3 years; P = 0.126) and RFS (88.4% vs. 84.4% at 3 years; P = 0.281) between post and pre-FSCs, respectively. Conclusions: Clinical fellowship training results in increase multidisciplinary referrals to supportive services, improves radiotherapy workflow, but had no significant impact on survival outcomes.

Validation of the FENCE Risk Groups for Prediction of Febrile Neutropenia With First-Cycle Chemotherapy.

BACKGROUND: The FEbrile Neutropenia after ChEmotherapy (FENCE) score was developed to estimate the risk of febrile neutropenia (FN) at first cycle of chemotherapy but has not been externally validated. We aimed to validate the FENCE score based on its risk groups in patients treated at a comprehensive cancer center. METHODS: We conducted a retrospective study of treatment-naïve adult patients with solid tumors and diffuse large B-cell lymphoma who received first-cycle chemotherapy between January and November 2019. Patients were followed until the second cycle of chemotherapy to identify any FN events (neutrophil count <0.5 × 109/L with fever ≥38.2°C). The FENCE score was determined and patients classified as low, intermediate, high, and very high risk. The discriminatory ability of classifying patients into FENCE risk groups was calculated as the area under the receiver operating characteristics curve and incidence rate ratios within each FENCE risk group. RESULTS: FN was documented during the first cycle of chemotherapy in 45 of the 918 patients included (5%). The area under the receiver operating characteristics curve was 0.66 (95% confidence interval [CI] = 0.58 to 0.73). Compared with the low-risk group (n = 285), the incidence rate ratio of developing FN was 1.58 (95% CI = 0.54 to 5.21), 3.16 (95% CI = 1.09 to 10.25), and 3.93 (95% CI = 1.46 to 12.27) in the intermediate (n = 293), high (n = 162), and very high (n = 178) risk groups, respectively. CONCLUSIONS: In this study, classifying patients into FENCE risk groups demonstrated moderate discriminatory ability for predicting FN. Further validation in multicenter studies is necessary to determine its generalizability.

Supportive Care Needs Assessment for Cancer Survivors at a Comprehensive Cancer Center in the Middle East: Mending the Gap.

BACKGROUND: Cancer survivors are often underprepared for what to expect post-treatment, and there are knowledge gaps regarding cancer survivors' supportive care needs in Jordan and neighboring Arab countries. This study aimed to identify gaps in supportive care needs among adult cancer survivors seen at King Hussein Cancer Center in Amman, Jordan, and explore predictors of unmet needs. METHODS: This was an observational cross-sectional study using a modified version of the Supportive Care Needs Survey 34 item short form (SCNS-SF34). RESULTS: Two hundred and forty adult cancer survivors completed the study questionnaire. The assessed needs were highest in the financial domain, including covering living expenses, managing cancer treatment adverse effects and co-morbidities. The least prevalent reported needs were in sexuality and reproductive consultations. Late-stage diagnosis was independently associated with higher physical, psychological, health system/information, financial and overall need scores, with p-values of 0.032, 0.027, 0.052, 0.002 and 0.024, respectively. The overall quality of life score was independently and inversely associated with physical, psychological, health system/information, financial and overall need domains, with p-values of 0.015, <0.0001, 0.015, 0.004 and 0.0003, respectively. CONCLUSIONS: This needs assessment identified problem areas for targeting interventions across the Jordanian cancer survivor population, and understanding these findings highlights opportunities for intervention to address gaps in care.

Moving Experience from North America to Developing Country to Approach a Desired Level of Quality Assurance in Head and Neck Radiation Therapy.

Evidence is lacking correlation between head and neck (HN) radiation oncology fellowship training and quality assurance (QA) round decision for plan modifications. This study was conducted to identify the association between training and changes in QA decisions. From 2007 to 2018, data on HN cancer cases presented at departmental QA rounds were prospectively collected. Then, we retrospectively analyzed the collected data to determine the impact of fellowship training on QA decisions. Cases were divided into pre-fellowship group (January 2007-September 2014) and post-fellowship group (October 2014-December 2018). Multivariable analysis (MVA) evaluated variables that could be associated with decreased frequencies of QA modification rates. From 2007 to 2018, 1266 HN cancer patients were identified; 728 patients were in the pre-fellowship group and 538 patients in the post-fellowship group. On MVA, fellowship training transformed QA decisions from more to less modifications (modified vs. approved; OR, 0.135; 95% CI, 0.076-0.240; p = 0.0001), increased approval rate for advanced T and N categories (T3-4 vs. T0-T2; OR, 0.798; 95% CI, 1.892-4.929; p = 0.0001 and N2-3 vs. N0-1; OR, 0.865; 95% CI, 1.454-3.423; p = 0.0002). By type of modification, fellowship training demonstrated a statistically significant reduction in rates of several types of modification that include target volume definition, target volume delineation, and dose (all p < 0.05). Our study determines the impact of the HN radiation oncology fellowship on decreased QA modification rates.

Extramedullary acute myeloid leukemia (eAML): Retrospective single center cohort study on clinico-pathological, molecular analysis and survival outcomes.

INTRODUCTION: extramedullary acute myeloid leukemia (eAML) is characterized by extramedullary tumor formation infiltrated by myeloid blasts, with or without maturation and effaced architecture. The clinical, genetic and molecular aspects and overall outcomes are well defined worldwide, but not well characterized in our region. PURPOSE AND METHODS: This is a retrospective single center cohort study on 32 patients, who were identified over 10 years to study the clinical, pathologic and genetic-molecular aspects, and survival outcomes. RESULTS: eAML is rare (1%), occurs at a younger age with male predominance. Central nervous system (CNS) with facial bone invasion is most commonly identified (34.4%). 45.5% were positive for conventional myeloid markers (MPO), CD33, CD117, and 36% positive for CD34 and CD68. 54% with normal karyotype had deleterious mutations on further testing. NGS revealed pathogenic mutations in 76%(N-9/17) and none tested positive for P53, IDH1 or IDH2. At a median follow up time of 43mo (range, 8.6-80mo); 37.5%(N-12) were in complete remission, 62.5%(N-20) relapsed. 28% of relapses were after allotransplant. 31%(N-10) alive and continued in complete remission(CR), and 69%(N-22) of patients have died.Median overall survival (OS) is 18.4 and relapse free survival (RFS) 18.7 months. OS and RFS were significantly better in patients, who attained CR after induction (IC 11.9 mo vs zero; P = 0.0001; IC 12mo vs zero; P = 0.0001) compared to patients with relapsed disease; and in patients who received allo-transplant consolidation with median OS and RFS 42 vs 8.5mo (P = 0.002) and 42months vs 10 mo (P = 0.006). Thus allotransplant may be considered for all eligible patients in first CR. CONCLUSION: achievement of complete remission after induction therapy is associated with improved outcomes in eAML. Allotransplant in first complete remission may be the most effective modality for achieving long-term remissions.

REVISED PREDICTIVE BIOMARKER FOR OCRIPLASMIN THERAPY IN VITREOMACULAR TRACTION DISORDERS.

PURPOSE: To determine a statistically optimal limit of adhesion size in vitreomacular traction (VMT) syndrome for ocriplasmin treatment. METHODS: In this retrospective, consecutive, interventional study, we included 106 patients treated with ocriplasmin injection because of VMT between July 2013 and January 2018. A univariate and multivariate risk analysis was performed with grouped factors and continuous factors. We used a receiver operating characteristic curve to measure the prognostic relevance of each continuous factor for therapy success and determined the statistically optimal cutoff value at which specificity and sensitivity are simultaneously maximized. RESULTS: Among the grouped factors, only a phakic lens status showed a highly significant positive influence on the resolution of the VMT. For the continuous factors, only the adhesion diameter before injection was a good predictor of anatomical success. The statistically optimal threshold value for the adhesion size was calculated to be 480 µm. Eyes below this limit had a 6.84-fold better chance of VMT resolution compared with eyes with a larger adhesion diameter. CONCLUSION: The threshold value of the VMT diameter for ocriplasmin therapy could be statistically defined as 480 µm and may thus be a new quantitative biomarker to predict treatment success.

Uniportal video-assisted versus open pneumonectomy: a propensity score-matched comparative analysis with short-term outcomes.

OBJECTIVES: Uniportal (U-VATS) pneumonectomy in lung cancer patients remains disputed in terms of oncological outcomes, and has not been compared to open approaches previously. We evaluated U-VATS versus open pneumonectomy at a high-volume centre. METHODS: Patients undergoing pneumonectomy for lung cancer between 2014 and 2018 were retrospectively reviewed and divided into two groups based on surgical approach. Propensity-score matching was performed (1:1), and intention-to-treat analysis applied. Overall survival, operative time, intraoperative blood loss, hospital-stay and readmission, pain, time to adjuvant therapy, morbidity and mortality were tested. Statistical analysis was performed using SAS version 9.4 (SAS Institute Inc. NC) RESULTS: 341 patients underwent pneumonectomy; 23 patients with small-cell lung cancer were excluded, thus 318 patients were submitted to surgery by either U-VATS (n = 54) or open (n = 264). After matching, 52 patients were selected from each group. Five patients (9.2%) in the uniportal group required conversion. There was no significant difference in intraoperative outcomes, complication rates, readmission rates or mortality. The U-VATS group experienced significantly shorter hospital stay (mean ± SD; 6.7 ± 2.7 vs 9.1 ± 2.3 days, p < 0.001) and reported less pain postoperatively (p < 0.0001). Adjuvant chemotherapy was initiated sooner after U-VATS (38.1 ± 8.4 vs 50.8 ± 11.5 days, p < 0.0001). Overall survival appeared to be superior in U-VATS when pathology stage was aligned (p = 0.001). CONCLUSIONS: Uniportal VATS is a safe and effective alternative approach to open surgery for pneumonectomy in lung cancer. Complications and oncologic outcomes were comparatively similar. U-VATS showed lower postoperative pain, shorter hospital stay and superior overall survival. The study is a preliminary analysis.

Transient ischemic dilatation with adenosine 99mTc-sestamibi stress: prognostic significance in patients with normal myocardial perfusion.

OBJECTIVE: To determine the significance of transient ischemic dilatation (TID) in patients with normal perfusion on adenosine stress/rest. METHODS: We analyzed 430 consecutive patients with normal perfusion on 2-day adenosine stress/rest 99mTc-sestamibi. A group of 70 patients with Framingham 10-year coronary heart disease risk < 10% was used to derive abnormal TID thresholds (derivation group). The significance of TID at these thresholds was validated in the remaining 360 patients (validation group) followed for cardiac events for 31.2 ± 9.7 (mean ± SD) months. RESULTS: Transient ischemic dilatation in the derivation group was 1.05 ± 0.13. Three definitions of an abnormal TID were used: > mean + 2SD (TID ≥ 1.32), > mean + 1SD (TID ≥ 1.19) and a TID in the group's highest quartile (TID ≥ 1.15). Of the 360 validation group patients, 12 (3.3%), 48 (13.3%) and 70 (19.4%) had TID ≥ 1.32, 1.19 and 1.15, respectively. Age, gender, family history of coronary artery disease (CAD), known CAD, smoking, hypertension, diabetes, dyslipidemia, rest LVEF, post-stress LVEF, ΔLVEF, ≥ 5% or 10% decrease in LVEF did not predict TID ≥ 1.32. However, TID ≥ 1.19 was predicted by rest LVEF and ≥ 5% decrease in LVEF (P = 0.04 and 0.02, respectively) and TID ≥ 1.15 was predicted by ≥ 5% decrease in LVEF (P = 0.02). Cardiac event-free survivals were similar in patients with a TID ≥ and < 1.32 (P = 0.68), ≥ and < 1.19 (P = 0.40) and ≥ and < 1.15 (P = 0.79). CONCLUSIONS: Transient ischemic dilatation does not confer adverse prognosis in patients with normal perfusion on adenosine stress/rest 99mTc-sestamibi irrespective of the threshold used for its definition.

Impact of 18F-FDG PET/CT, CT and EBUS/TBNA on preoperative mediastinal nodal staging of NSCLC.

BACKGROUND: Staging of non-small-cell lung cancer (NSCLC) is a multidisciplinary process involving imaging, endoscopic and surgical techniques. This study aims at investigating the diagnostic accuracy of 18F-FDG PET/CT, CT scan, and endobronchial ultrasound/transbronchial needle aspirate (EBUS/TBNA) in preoperative mediastinal lymph nodes (MLNs) staging of NSCLC. METHODS: We identified all patients who were diagnosed with NSCLC at the King Hussein Cancer Center in Amman, Jordan, between July 2011 and December 2017. We collected their relevant clinical, radiological, and histopathological findings. The per-patient analysis was performed on all patients (N = 101) and then on those with histopathological confirmation (N = 57), followed by a per-lymph-node-station basis overall, and then according to distinct N-stage categories. RESULTS: 18F-FDG PET/CT, in comparison to CT, had a better sensitivity (90.5% vs. 75%, p = 0.04) overall and in patients with histopathological confirmation (83.3% vs. 54.6%), and better specificity (60.5% vs. 43.6%, p = 0.01) overall and in patients with histopathological confirmation in MLN staging (60.6% vs. 38.2%). Negative predictive value of mediastinoscopy, EBUS/TBNA, and 18F-FDG PET/CT were (87.1%), (90.91%), and (83.33%) respectively. The overall accuracy was highest for mediastinoscopy (88.6%) and EBUS/TBNA (88.2%), followed by 18F-FDG PET/CT (70.2%). Dividing patients into N1 disease vs. those with N2/N3 disease yielded similar findings. Comparison between 18F-FDG PET/CT and EBUS/TBNA in patients with histopathological confirmation shows 28 correlated true positive and true negative findings with final N-staging. In four patients, 18F-FDG PET/CT detected metastatic MLNs that would have otherwise remained undiscovered by EBUS/TBNA alone. Lymph nodes with a maximal standardized uptake value (SUVmax) more than 3 were significantly more likely to be true-positive. CONCLUSION: Multimodality staging of the MLNs in NSCLC is essential to provide accurate staging and the appropriate treatment. 18F-FDG PET/CT has better overall diagnostic utility when compared to the CT scan. The NPV of 18F-FDG PET/CT in MLNs is reliable and comparable to the NPV of EBUS/TBNA. SUVmax of MLNs can help in predicting metastases, but nevertheless, a positive 18F-FDG PET/CT MLNs particularly if such a result would change the treatment plan, should be verified histopathologically.

Expression of PD-L1 using SP142 CDx in triple negative breast cancer.

Triple negative breast cancer (TNBC) represents a small subtype of breast cancer yet it has the worst outcome. Immunotherapy using immune checkpoint inhibitors combined with chemotherapy was recently approved by the FDA raising the hope for an improved outcome. The approval was based on demonstration of a positive PD-L1 expression using the SP142 CDx assay 1. We aimed to study a cohort of TNBC patients in terms of prevalence of the PD-L1 expression using the approved assay and to investigate its association with clinicopathological variables. This is a single center retrospective study consisting of 49 TNBC patients who had available archived paraffin-embedded tissue blocks from the primary tumors. All blocks were stained using the SP142 CDx assay as per the manufacture's instruction. Clinicopathological data were collected from medical records. Eighteen of the 49 (36.7%) patients were found to have a score of 1% or more by the immune cell-scoring algorithm. PDL-1 expression was significantly associated with the degree of tumor infiltrating lymphocytes (TILs). No additional significant relationship was found between PD-L1 expression and any of the other investigated clinicopathological variables. Although a trend of favorable prognostic association with PD-L1 expression was noted. The overall and event free survival were significantly related to pathological response to neoadjuvant therapy. Conclusion: Our PD-L1 rate of 36.7% is close to the results of the previously reported 40.9% in the IMpassion 130 trial. There were no significant association between positive PD-L1 expression and clinicopathological variables however a trend of a favorable outcome was observed.

Evaluating the Predictive Value of Lactate in Patients With Cancer Having Septic Shock.

PURPOSE: Limited studies evaluated the predictive value of serum lactate (LA) in critically ill patients with cancer. The main objective of this study was to evaluate the predictive validity of LA single measurements as well as LA clearance in predicting mortality in patients with cancer having septic shock. The study also aimed to determine the LA measurement over the first 24 hours with the highest predictability for hospital mortality. MATERIALS AND METHODS: A retrospective cohort study of adult patients with cancer having septic shock and LA measurements during the first 24 hours. Three receiver-operating characteristic (ROC) curves were constructed to evaluate the predictive validity for hospital mortality of LA at baseline, at 6 hours and at 24 hours after identifying septic shock. The ROC with the largest area under the curve was analyzed to determine LA level with the highest predictability for hospital mortality. In addition, the ability of LA normalization (LA <2 mmol/L at 6 hours and at 24 hours) and the degree of LA elimination (>10% and >20% at 24 hours) to predict hospital mortality were evaluated by determining the predictive values for each clearance end point. RESULTS: The study included 401 patients. LA >2.5 mmol/L at 24 hours showed the largest area under the ROC curve to predict hospital mortality (ROC area: 0.648; 95% confidence interval: 0.585-0.711) with a sensitivity of 58.4% and specificity of 62.8%. The LA normalization, LA clearance >10%, and LA clearance >20% were also predictors of hospital mortality, with the highest sensitivity for LA normalization at 6 hours (74%) and LA normalization at 24 hours (73.4%). CONCLUSION: In patients with cancer having septic shock, LA >2.5 mmol/L at 24 hours of septic shock had the highest predictability for hospital mortality. The LA normalization and clearance were also predictors of hospital mortality. However, all LA end points were not strong predictors.

Clinicopathological Characteristics And Treatment Outcomes Of Breast Cancer Among Adolescents And Young Adults In A Developing Country.

PURPOSE: Compared to Western societies, breast cancer diagnosis in our region is usually made at a younger age and at a more advanced stage. Breast cancer in younger patients tends to be more aggressive, and may result in a higher likelihood of long-term treatment-related toxicity and unique psychosocial problems. This study highlights the clinicopathological features and treatment outcomes in this age-group in a developing country like ours. METHODS: Consecutive patients aged 40 years or younger with a pathologically confirmed diagnosis of breast cancer treated and followed up at our institution were included. Medical records and hospital databases were searched for patients' characteristics and treatment outcomes. RESULTS: A total of 417 patients were enrolled. Median age at diagnosis was 35 (21-40) years. On presentation, 63 (15.1%) patients had metastatic disease, 50 (79.4%) with visceral metastasis. Patients with nonmetastatic disease had poor pathological features, including node-positivity (66.9%), grade III (51.4%), lymphovascular invasion (48.6%) and positive HER2 (31.5%). Breast-conserving surgery was performed on 32.9%, and only 36.5% of women had breast-reconstruction surgery. At a median follow-up of 59 months, 5-year overall survival for the whole group was 72%: 84% for nonmetastatic and 13% for those with metastatic disease. On Cox regression, nodal metastasis (adjusted HR 3.46, 95% CI 1.48-8.10; p=0.004) and grade III disease (HR 1.97, 95% CI 1.14-3.39; p=0.015) were associated with poor outcome. CONCLUSION: Adolescents and young Jordanian adults with breast cancer present with more advanced-stage disease and more aggressive pathological features that reflect poorly on treatment outcomes.

Intensity of Cancer Care Near the End of Life at a Tertiary Care Cancer Center in Jordan.

CONTEXT: Chemotherapy use in the last month of life is an indicator of poor quality of end-of-life care. OBJECTIVES: We assessed the frequency of chemotherapy use at the end of life at our comprehensive cancer center in Jordan and identified the factors associated with chemotherapy use. METHODS: We conducted a retrospective chart review to examine the use of chemotherapy in the last 30 days and 14 days of life in consecutive adult patients with cancer seen at King Hussein Cancer Center (KHCC) who died between January 1, 2010, and December 31, 2012. We collected data on patient and disease characteristics, palliative care referral, and end-of-life care outcome indicators. RESULTS: Among the 1714 decedents, 310 (18.1%) had chemotherapy use in the last 30 days and 142 (8.3%) in the last 14 days of life. Over half (910; 53.1%) had a palliative care referral. Chemotherapy use in the last 30 and 14 days of life were associated with younger age (odds ratio [OR] 0.99/yr, P = 0.01, and OR 0.99/yr, P = 0.01, respectively) and hematological malignances (OR 1.98, P < 0.001, and OR 2.85, P < 0.001, respectively). Palliative care referral was significantly associated with decreased use of chemotherapy in the last 30 (OR 0.30, P < 0.001) and 14 (OR 0.15, P < 0.001) days of life. CONCLUSIONS: A sizable minority of patients with cancer at KHCC received chemotherapy at the end of life. Younger patients and those with hematological malignancies were more likely to receive chemotherapy, whereas those referred to palliative care were significantly less likely to receive chemotherapy at the end of life.

Four cycles of adriamycin and cyclophosphamide followed by four cycles of docetaxel (NSABP-B27) with concomitant trastuzumab as neoadjuvant therapy for high-risk, early-stage, HER2-positive breast cancer patients.

BACKGROUND: The majority of breast cancer patients in Jordan are diagnosed at a young age and present with metastatic or locally advanced disease. The National Surgical Adjuvant Breast and Bowel Project Protocol B27 (NSABP-B27) (four cycles of adriamycin and cyclophosphamide [AC] followed by four cycles of docetaxel) is a standard neoadjuvant regimen in our institution. In this study, we report the efficacy of adding trastuzumab to docetaxel in this regimen for high-risk human epidermal growth factor receptor 2 (HER2)-positive early-stage disease. PATIENTS AND METHODS: Consecutive HER2-positive breast cancer patients treated with this regimen were included. Treatment was given at standard doses and schedules as reported in NSABP-B27. Trastuzumab was given with docetaxel and then continued for 1 year. RESULTS: A total of 121 patients (mean age 45.4 years) were included. The majority had high-risk features including large tumor size, positive axillary lymph nodes, and grade III disease. Three patients did not complete the planned cycles of AC due to a lack of response. Eight (6.6%) patients missed at least one cycle of docetaxel. Following neoadjuvant therapy, 119 patients underwent surgery, of whom 59 (49.6%) patients achieved pathological complete response. The response was higher in node-negative patients (64.0 vs 45.7%; P=0.03) and in hormone receptor-negative disease patients (69.7 vs 41.9%; P=0.018). Breast-conserving surgery was performed in 21.5% of the patients. The median disease-free survival (DFS) for the whole group was not reached while the 3- and 5-year DFS rates were 84.2 and 74.1%, respectively. CONCLUSION: Trastuzumab added to the NSABP-B27 regimen is a unique combination. When used in high-risk patients, as in our study, outcomes similar to reported data were achieved without unexpected toxicities.

Thromboembolic events in cancer patients on active treatment with cisplatin-based chemotherapy: another look!

BACKGROUND: The risk of thromboembolic events is higher among cancer patients, especially in patients undergoing chemotherapy. Cisplatin-based regimens claim to be associated with a very high thromboembolic rate. In this study, we report on our own experience with thrombosis among patients on active cisplatin-based chemotherapy. METHODS: Medical records and hospital databases were searched for all the patients treated with any cisplatin-based regimen for any kind of cancer. Thrombosis was considered cisplatin-related if diagnosed any time after the first dose and up to 4 weeks after the last. The Khorana risk assessment model was performed in all cases. RESULTS: A total of 1677 patients (65.5% males, median age: 50 years) treated with cisplatin-based regimens were identified. Head and neck (22.9%), lung (22.2%), lymphoma and gastric (11.4% each) were the most common primary tumors. Thromboembolic events were reported in 110 (6.6%); the highest was in patients with gastric cancer (20.9%) and the lowest in patients with head and neck cancers (2.3%) and lymphoma (1.6%). Thrombosis included deep vein thrombosis (DVT) in 69 (62.7%), pulmonary embolism (PE) in 18 (16.9%) and arterial thrombosis in 17 (15.6%). A majority (51.1%) of the patients had stage IV disease and only 16% had stage I or II.In a multivariate analysis, significantly higher rates of thrombosis were associated with gastric as the primary tumor, advanced-stage disease, female sex but not age, and the Khorana risk score or type of cisplatin regimen. While the presence of CVC was significantly associated with the risk of thrombosis (p < 0.0001) in the univariate analysis, and such significance was lost in the multivariate analysis (odds ratio, 1.098; 95%CI, 0.603-1.999, p = 0.7599). CONCLUSIONS: Thromboembolic events in cancer patients on active cisplatin-based chemotherapy were commonly encountered. Gastric cancer, regardless of other clinical variables, was associated with the highest risk.