Treatment Patterns,Health Care Resource Utilization,and Cost in Patients with Myelofibrosis in the United States

BackgroundThis study analyses treatment patterns, health care resource utilization (HCRU), and costs in patients with myelofibrosis (MF) and a subgroup treated with ruxolitinib (RUX).Materials and MethodsTreatment patterns, all-cause and MF-related HCRU, and costs were analyzed in adults with MF with continuous enrollment in a commercial or the Medicare Advantage health plan in the pre-index period, defined as the 12 months immediately prior to the index date (date of primary or secondary MF diagnosis), and the post-index period, defined as ≥6 months following the index date. In a subgroup analysis, outcomes were analyzed in patients treated with optimal RUX (OPT RUX, ≥30 mg) and suboptimal RUX (SUB RUX, <30 mg) in the pre-index RUX period, defined as the 3 months immediately prior to the index RUX date (first date for an RUX claim), and the post-index RUX period, defined as ≥6 months following the index RUX date.ResultsOf 2830 patients with an MF diagnosis, 1191 met eligibility requirements. The median age of patients was 72 years, 54% were male, and comorbidities were frequent. Sixty percent of patients received ≥1 line of therapy (LOT), of which 46% (n = 331) had ≥2 LOTs during the post-index MF period. Costs increased considerably 6-month pre-index to 6-month post-index (all-cause: cause ($24,216 to $48,966) and MF-related ($16,502 to $39,383), driven by inpatient stays and pharmacy costs. In the subgroup analysis, patients treated with RUX (n = 495) experienced significant disease burden and high costs, regardless of dose. A shorter duration of therapy and a higher rate of discontinuation were observed in patients treated with SUB RUX (n = 191) versus OPT RUX (n = 304).ConclusionThese findings suggest a significant disease and economic impacts associated with MF patients that persists with RUX therapy, highlighting the need for additional therapeutic options for MF.     

Aberrant Expression of CD13 Identifies a Subgroup of Standard-Risk Adult Acute Lymphoblastic Leukemia With Inferior Survival

BackgroundThe standard-risk (SR) subgroup of acute lymphoblastic leukemia in adults (aALL) is a heterogeneous category, with a 20% to 40% relapse rate and a wide range of relapse-free survival (RFS) and overall survival (OS). There is a need to identify at the outset those patients with SR-aALL who are likely to have shorter RFS and OS, so they can be treated more aggressively.Patients and MethodsFlow cytometric data of 81 patients with SR-aALL treated with a standardized protocol were retrospectively analyzed. Thirty-two patients (40%) relapsed; the median RFS and OS were 12.5 months (range, 1-136 months) and 30 months (range, 3-235 months), respectively. Twenty-six patients survived ≥ 48 months.ResultsExpression of myeloid antigen CD13, using the conventional ≥ 20% threshold and a lower ≥ 5% threshold, was seen in 17 (29%) of 59 and 29 (49%) of 59 patients, respectively, whereas dual expression of CD13 and CD33 was seen in 8 patients. CD13 positivity at ≥ 20% and ≥ 5% threshold was associated with a shorter RFS (P = .0158 and P < .0001, respectively) and OS (P = .0072 and P < .0001, respectively). Dual expression of CD13 (at ≥ 5% or ≥ 20% threshold) and CD33 was associated with inferior OS (P = .0038 and P = .0032, respectively) and RFS (P = .0705 and P = .2516, respectively). For ≥ 20% and ≥ 5% threshold of positivity, 16 of 42 and 28 of 42 who survived < 48 months were positive, compared with 1 of 17 and 1 of 17 who survived ≥ 48 months (P = .0133 and P < .0001, respectively).ConclusionAberrant expression of CD13 in ≥ 5% of blasts of patients with SR-aALL is an adverse prognostic factor, delineating a subgroup of patients with SR-aALL that should be considered for more aggressive treatment.     

Day 14 Bone Marrow Evaluation During Acute Myeloid Leukemia Induction in a Real-world Canadian Cohort

IntroductionThe 2017 National Comprehensive Cancer Network guidelines for acute myeloid leukemia have recommended performing bone marrow (BM) aspiration and BM trephine biopsy (BMTB) 14 to 21 days after starting induction therapy (commonly referred to as “day 14 [D14] marrow”). Those who do not achieve a hypoplastic marrow, with cellularity < 20% and blasts < 5%, are recommended to undergo 2-cycle induction (2CI). We performed a retrospective analysis to determine the impact of D14 BM characteristics in predicting for remission, association with overall survival (OS), and the effect of 2CI according to the D14 BM results.Patients and MethodsPatients aged 18 to 70 years undergoing induction therapy with standard “7 + 3” regimens were included. D14 cellularity was determined from BMTB samples and the blast percentage was assessed by morphology on BM aspiration and BMTB samples. The outcomes evaluated included the rates of complete remission (CR) and OS.ResultsA total of 486 patients with results from D14 BM evaluation were included in the present study. On multivariate analysis, cytogenetic risk and D14 blasts < 5% were predictive of CR/CR with incomplete count recovery (P < .001). Cytogenetic risk (P < .001), age < 60 years (P = .001), and D14 blasts < 5% (P = .045) predicted for OS. 2CI was performed in 131 patients (27%). Patients with hypocellular D14 BM but residual blasts (n = 106) underwent 2CI in 46% of cases, with improved remission rates (43.9% vs. 72.0%; P = .004) but no difference in OS.ConclusionsThe results from D14 BM evaluations are predictive of subsequent remission and OS. Our findings did not show a survival benefit with D14 BM-driven 2CI.     

Retrospective Analysis of Prognostic Factors Associated With Response and Overall Survival by Baseline Marrow Blast Percentage in Patients With Myelodysplastic Syndromes Treated With Decitabine

BackgroundAfter the World Health Organization (WHO) changed the definition of acute myeloid leukemia (AML) to ≥ 20% blasts, the International Working Group (IWG) response criteria for myelodysplasia were updated. This retrospective analysis evaluated response to decitabine using updated IWG criteria in patients pooled from 2 decitabine trials.Patients and MethodsOutcomes for patients with myelodysplastic syndrome (MDS) with baseline marrow blasts ≥ 20% and < 30% (RAEB-t group) and < 20% (MDS group) were compared.ResultsPatients with RAEB-t (n = 26) had a significantly shorter time from diagnosis to study treatment (7.3 vs. 18.3 months), a higher International Prognostic Scoring System (IPSS) risk (77% vs. 16% high-risk patients), and lower median baseline platelet count (62.3 vs. 112.7 × 10³/μL) vs. patients with MDS (n = 157), yet no significant difference in overall response rate (ORR) (15.4% vs. 28.0%). Patients with MDS had better duration of response (9.9 vs. 5 months; P = .024) and overall survival (OS) (16.6 vs. 9.0 months; P = .021) compared with patients with RAEB-t.ConclusionDecitabine is active in and may benefit patients with > 20% blasts (RAEB-t).     

Impact of Systemic Therapy in Metastatic Renal-Cell Carcinoma Patients With Synchronous and Metachronous Brain Metastases

BackgroundModern radiation techniques have led to significant improvements in intracranial disease control and overall survival (OS) for metastatic renal-cell carcinoma (mRCC) patients diagnosed with brain metastases (BM). The impact of systemic therapy in patients developing mRCC BM remains undercharacterized.Patients and MethodsWe performed a retrospective cohort study of mRCC patients diagnosed with BM. Patients were grouped as having either metachronous BM (ie, ≥ 3 months from mRCC diagnosis) or synchronous BM (ie, < 3 months from mRCC diagnosis). Details of patient demographics, BM, systemic therapy, and outcomes were extracted. Statistical analysis comprised chi-square tests, analysis of variance, and Kaplan-Meier method to characterize survival outcomes.ResultsSeventy-four patients were identified (40 at ≥ 3 months from mRCC diagnosis and 34 at < 3 months from mRCC diagnosis) of which 72 (97%) received local therapy for their BM. Median (interquartile range [IQR]) duration while first line treatment was longer at 7.8 (3.6-17.0) versus 5.1 (3.3-12.6) in patients with metachronous BM versus patients with synchronous BM (P = 0.6), respectively. After BM diagnosis, the metachronous BM cohort continued to receive the same systemic therapy for a median (IQR) duration of 1.9 (0.4-5.5) months, with eventual change most commonly the result of extracranial disease progression. Median (IQR) OS from mRCC diagnosis favored metachronous BM patients versus synchronous BM patients, at 64.2 (31.4-not yet reached) versus 22.4 (9.7-34.1) months (P = .003), respectively. However, this was not significantly different from the time of BM diagnosis, with median (IQR) survival of 20.6 (9.2-31.2) versus 15.7 (11.6-not yet reached) months (P = .95), respectively.ConclusionProlonged OS was found for mRCC patients with BM that presented either metachronously or synchronously. For patients diagnosed with metachronous BM, the development of BM may be an early sign of systemic therapy failure.     

Practical Measures of Clinical Benefit With Ruxolitinib Therapy: An Exploratory Analysis of COMFORT-I

BackgroundThe phase III COMFORT (Controlled Myelofibrosis Study With Oral JAK inhibitor Treatment)-I and COMFORT-II trials in patients with intermediate-2 or high-risk myelofibrosis (MF) showed that ruxolitinib was superior to placebo and best available therapy, respectively, for improvements in spleen volume, MF-related symptoms, and overall survival (OS). However, patients managed in community settings might not have access to the methods used in the COMFORT trials. In this exploratory analysis we summarize efficacy findings of COMFORT-I using practical, community-oriented measures of patient outcomes.Patients and MethodsIn this post hoc analysis of data from COMFORT-I we evaluated changes from baseline to week 12 in spleen size (palpable length and volume), patient-reported outcomes (Patient Global Impression of Change; Myelofibrosis Symptom Assessment Form; Patient-Reported Outcomes Measurement System Fatigue Scale), body weight, and serum albumin levels in 5 subgroups of ruxolitinib-treated patients on the basis of week 12 spleen length changes from baseline: (1-4) ≥ 50%, 25% to < 50%, 10% to < 25%, or < 10% reduction; and (5) worsening. OS was evaluated in ruxolitinib-treated patients with week 12 spleen length reductions from baseline ≥ 50%, 25% to < 50%, or < 25% (including worsening).ResultsIn all spleen length subgroups, including patients with worsening spleen length at week 12, ruxolitinib (n = 150) was associated with improvements in spleen volume, patient-reported symptom burden, body weight, and serum albumin levels. Greater reductions in spleen length were associated with prolonged OS.ConclusionA variety of assessment methods beyond palpable spleen length that are easily accessible in the community setting might be useful in evaluating the clinical benefit of ruxolitinib over time in patients with MF.     

Clinical and Prognostic Features of Essential Thrombocythemia: Comparison of 2001 WHO Versus 2008/2016 WHO Criteria in a Large Single-center Cohort

BackgroundAccording to 2008/2016 classification of the World Health Organization (WHO), a platelet (PLT) count ≥ 450 × 10⁹/L, reduced from the previously published WHO 2001 indicated level ≥ 600 × 10⁹/L, was considered the new PLT threshold for the diagnosis of essential thrombocythemia (ET).Patients and MethodsTo validate this important diagnostic change in a setting of current clinical practice, we retrospectively analyzed clinical and hematologic features at diagnosis and during follow-up of 162 patients with ET, diagnosed in our center from January 2008 to December 2017. We subdivided patients according to PLT value at baseline into Group A (PLT ≥ 600 × 10⁹/L) (124 patients; 76.5%) and Group B (PLT ≥ 450 × 10⁹/L < 600 × 10⁹/L) (38 patients; 23.5%).ResultsAmong clinical features, only the median value of leukocytes (P < .001) was significantly higher in Group A. Cytostatic treatment was administered in 103 patients, with a significantly higher rate in patients of group A (P < .001). After a median follow-up of 42.4 months (interquartile range, 22.1-70.6 months), 8 thrombotic events were recorded in the entire cohort, without differences between the 2 groups (P = .336). The 5-year overall survival (OS) of the entire cohort was 96.9% (95% confidence interval, 92.6%-100%), without differences between the 2 groups (P = .255).ConclusionsOur data indicate a substantial homogeneity among patients with ET regardless of the PLT count at diagnosis, thus confirming the usefulness of the 2008/2016 WHO diagnostic criteria.     

Prognostic and Therapeutic Value of Day 14 Bone Marrow Aspiration in Adult Acute Myeloid Leukemia Patients

BackgroundEarly blast clearance to induction chemotherapy in acute myeloid leukemia (AML) is an important prognostic indicator of treatment outcome in addition to genetics and molecular genetics. We evaluated the prognostic value of bone marrow aspiration (BMA) at day 14 (D14) and impact on outcome to asses the timing of a second induction.Patients and MethodsThis retrospective study included 303 adult AML patients managed at the National Cancer Institute, Cairo University, from the beginning of 2010 to the end of 2014.ResultsMedian age was 34 years (range, 18-67 years). Sixty-six percent had early blast clearance with < 5% blasts and 34% had ≥ 5% blasts at BMA D14; 38 patients died early during or shortly after induction. Initial blast load (bone marrow and peripheral blood) and initial platelet count were significantly higher in those with disease that did not respond to therapy compared to those whose disease did respond to therapy at D14 (P < .001, .035, and .006, respectively). The median disease-free survival for early blast clearance at D14 was 18.5 months, versus 18.7 months for those with late response to therapy (day 28), and was only 1.3 months for patients who received immediate second-line therapy on the basis of BMA D14 (P < .001). The median overall survival for early blast clearance was 13.6 months, versus 7.2 months for those with late response to therapy, and only 1.3 months for patients who received immediate second-line therapy on the basis of BMA D14 (P < .001).ConclusionBMA D14 has a significant prognostic impact on the therapeutic outcome of AML patients (complete remission, disease-free survival, and overall survival); however, a second induction in patients with BMA D14 blasts > 5% should be delayed until neutrophil recovery to minimize death in aplasia.     

Prognostic Value of the Combination of Circulating Tumor Cells Plus KRAS in Patients With Metastatic Colorectal Cancer Treated With Chemotherapy Plus Bevacizumab

ObjectiveCirculating tumor cells (CTCs) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) status were identified as prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab in analyses of the MACRO (Maintenance Treatment in Advanced Colorectal Cancer) trial. In this post hoc analysis of the MACRO trial, the potential additive effect of these 2 factors on patient outcomes was explored.MethodsA total of 158 of the 480 patients involved in the MACRO trial were included in the biological marker substudy. CTC isolation and enumeration were centralized and performed using the CellSearch System (Veridex LLC, Raritan, NJ) in 7.5 mL of whole blood. Evaluation of KRAS status was performed retrospectively by the standard method used at each center. PFS and OS were analyzed by the Kaplan–Meier method according to CTC count and KRAS status.ResultsPatients with < 3 CTC per 7.5 mL blood at baseline and KRAS wild-type tumors had a median PFS of 14.2 months compared with 6.2 months in patients with ≥ 3 CTCs and KRAS mutated tumors (P < .0001; hazard ratio, 3.0; 95% confidence interval, 1.8-5.2). Similar findings were observed for OS (28.9 and 13.7 months, respectively, P = .0004; hazard ratio 2.8; 95% confidence interval, 1.6-4.9). Multivariate analyses showed that CTC count ≥ 3 and KRAS status were the only independent prognostic factors for both PFS and OS.ConclusionsThis post hoc analysis showed that CTC count and KRAS status were independent prognostic factors for outcomes in patients with metastatic colorectal cancer treated with bevacizumab ± chemotherapy. These factors should be taken into account in the design of future phase III trials.     

Sarcomatoid Dedifferentiation in Metastatic Clear Cell Renal Cell Carcinoma and Outcome on Treatment With Anti–Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors: A Retrospective Analysis

IntroductionThis study aimed to assess the efficacy of anti–vascular endothelial growth factor receptor tyrosine kinase inhibitors (anti-VEGFR-TKIs) in patients with metastatic clear cell renal cell carcinoma (m-ccRCC) with sarcomatoid dedifferentiation.Patients and MethodsThe files of all patients with m-ccRCC consecutively treated with first-line anti-VEGFR-TKIs at the authors' institution were retrospectively reviewed. Pathology slides from nephrectomy and metastasectomy were assessed for the presence and extent of sarcomatoid dedifferentiation.ResultsA total of 124 patients were included; nephrectomy and metastasectomy specimens were available in 117 and 35 patients, respectively. Thirty percent of the primary nephrectomy specimens had sarcomatoid features, and the median involvement of the sarcomatoid component was 21% (range, 1%-95%). Patients with an important sarcomatoid component, defined as ≥ 25% involvement of the tumor, had a very poor outcome: progression-free survival (PFS) and overall survival (OS) were 3 and 6 months, respectively, and no partial responses (PR) were observed. Patients without sarcomatoid dedifferentiation or with sarcomatoid involvement < 25% had a PFS of 12 months (P < .0001; hazard ratio [HR], 51; 95% CI, 12.58-207.3), an OS of 22 months (P < .0001, HR, 10.72; 95% CI, 3.56-32.25), and a PR rate of 50% (P = .0015). Patients with a sarcomatoid component ≥ 25% in the metastasectomy also had a poorer PFS and OS on anti-VEGFR-TKIs compared with patients with < 25% of sarcomatoid features at these sites.ConclusionPatients with m-ccRCC whose tumors contain a component of sarcomatoid dedifferentiation of ≥ 25% of the total tumor volume have a very poor outcome when treated with anti-VEGFR-TKIs. Analysis of the extent of sarcomatoid features in resected metastases can provide additional prognostic information.     

Day +100 Platelet Count Predicts Survival After Allogeneic Hematopoietic Stem-Cell Transplantation in Children With Hematologic Malignancies

IntroductionRecovery of platelet count by day 100 after hematopoietic stem-cell transplantation (HSCT) is affected by many factors and has been reported to be a predictor of overall survival (OS) in a variety of diseases and donor types. We investigated the correlation between day +100 platelet count and OS after allogeneic HSCT in a relatively homogeneous cohort of pediatric patients with hematologic malignancies.Patients and MethodsWe conducted a retrospective study of 152 consecutive patients who underwent allogeneic HSCT at the Children’s Cancer Hospital Egypt between 2009 and 2015 with a minimum follow-up duration of 1 year after transplantation. All eligible patients received myeloablative conditioning, and all had matched related donors. Patients who survived without relapse until day 100 after HSCT were divided into 2 groups: early platelet recovery (EPR; platelet count ≥ 100 × 10⁹/L at day +100 after transplantation) and delayed platelet recovery (DPR; platelet count < 100 × 10⁹/L at day +100 after transplantation).ResultsAt day +100, 113 patients (74%) had EPR and 39 patients (26%) had DPR. With a median follow-up of 41 months (range, 12-93 months), 41 patients (27.2%) died, 35 of relapsed disease. The 3-year disease-free survival (DFS) and OS were 68 ± 7.84% and 71.9 ± 7.84%, respectively. The 3-year OS was 77.9% in the EPR group and 57.1% in the DPR group (P = .006). Three-year DFS of the EPR and DPR groups were 73.2 ± 9% and 54.8 ± 16.3%, respectively (P = .02). Incidence of disease relapse for EPR and DPR patients was 22.6% and 39.5%, respectively (P = .04). Multivariate analysis for survival identified DPR as a predictor of decreased survival (P = .002).ConclusionPatients with a robust platelet count at day 100 are likely to do well. However, patients who do not experience a platelet count of ≥ 100 × 10⁹/L have inferior long-term OS and DFS and may require further evaluation at the day 100 time point.     

Stereotactic Body Radiotherapy for Centrally Located Primary Non–Small-Cell Lung Cancer: A Meta-Analysis

BackgroundThe purpose of the study was to evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for centrally located, primary non–small-cell lung cancer (NSCLC).Materials and MethodsSystematic search of 4 databases (PubMed, MEDLINE, EMBASE, and Cochrane Library) was performed for literature published until May 9, 2018. Primary (overall survival [OS] and local control [LC] rates) and secondary (Grade ≥3 toxicity) endpoints were reported.ResultsThirteen studies encompassing 599 patients with central NSCLCs were included. Median values of T1 tumor proportion, tumor size, and median survival were 55.3% (range, 0%-75%), 3.3 (range, 2.1-4.1) cm, and 26 (range, 14-68.9) months, respectively. Pooled rates of 1-, 2-, and 3-year OS rates were 84.3% (95% confidence interval [CI], 75.7-90.3), 64.0% (95% CI, 52.9-72.2), and 50.5% (95% CI, 39.4-61.5), respectively. Pooled rates of 1-, 2-, and 3-year LC rates were 89.4% (95% CI, 80.8-94.4), 82.2% (95% CI, 71.7-89.4), and 72.2% (95% CI, 55.0-84.7), respectively. Pooled rate of Grade ≥3 complication was 12.0% (95% CI, 7.3-19.0). Meta-regression analyses showed significant positive relationships between biologically equivalent dose using an α/β of 10 Gy in the linear quadratic model (BED_10Gy) and 1- and 2-year LC rates (P < .001 and P < .001), and 1- and 2-year OS rates (P = .0178 and P = .032), and Grade ≥3 complication rate (P = .0029). In subgroup comparisons between BED_10Gy <100 Gy versus ≥100 Gy, 1- and 2-year LC rates were significantly different but not for OS and Grade ≥3 complication rates.ConclusionOur results suggests that SBRT is potent for tumor control in central NSCLC, although complications should be further minimized through optimization of dose-fractionation scheme and accurate planning. Using BED_10Gy ≥100 Gy yielded higher LC rates, and dose escalation was related to OS, LC, and complications.     

Annual Facility Treatment Volume and Patient Survival for Mycosis Fungoides and Sézary Syndrome

BackgroundManagement of mycosis fungoides and Sézary syndrome (MF/SS) is complex, and randomized evidence to guide treatment is lacking. The institutional treatment volumes for MF/SS might vary widely nationally and influence patient survival.Patients and MethodsUsing the National Cancer Database, we identified patients with a diagnosis of MF/SS from 2004 to 2011 in the United States who had received treatment at a reporting facility. The patients were grouped into quintiles according to their treatment facility's average annual treatment volume (ATV). The characteristics associated with ATV were identified and compared using χ² tests. Overall survival (OS) was compared among the ATV quintiles using the Kaplan-Meier method with log-rank tests and multivariable Cox regression with hazard ratios (HRs). OS was also analyzed using the annual patient volume as a continuous variable.ResultsA total of 2205 patients treated at 374 facilities were included for analysis. The ATV quintile cutoffs were 1, 3, 6, and 9 patients. With a median follow-up period of 59 months, the 5-year estimated OS survival increased with ATV from 56.7% in the lowest quintile (≤ 1 patient annually) to 83.8% in the highest quintile (> 9 patients annually; P < .001). On multivariable analysis, greater ATV was associated with improved survival when analyzed as a continuous variable (HR, 0.96 per patient per year; 95% confidence interval, 0.94-0.98; P < .001) and when comparing the highest quintile to the lowest quintile (HR, 0.46; 95% confidence interval, 0.39-0.55).ConclusionThe present national database analysis demonstrated that higher facility ATV is associated with improved OS for patients with MF/SS. Further study is needed to determine the underlying reasons for improved survival with higher facility ATV.     

Upfront and Repeated Stereotactic Radiosurgery in Patients With Brain Metastases From NSCLC

IntroductionApproximately 40% of non-small-cell lung cancer (NSCLC) patients develop brain metastases (BM). Stereotactic radiosurgery (SRS) instead of whole-brain radiotherapy (WBRT) is increasingly administered as an upfront treatment to patients with a limited number of BM. We present outcomes and validation of prognostic scores for these patients treated with upfront SRS.MethodsWe retrospectively analyzed 199 patients with a total of 268 SRS courses for 539 brain metastases. Median patient age was 63 years. For larger BM, dose reduction to 18 Gy or hypofractionated SRS in 6 fractions was applied. We analyzed the BMV-, the RPA-, the GPA- and the lung-mol GPA score. Cox proportional hazards models with univariate and multivariate analyses were fitted for overall survival (OS) and intracranial progression-free survival (icPFS).ResultsSixty-four patients died, 7 of them of neurological causes. Thirty eight patients (19,3%) required a salvage WBRT. Median OS was 38, 8 months (IQR: 6-NA). In univariate analysis as well as multivariate analysis, the Karnofsky performance scale index (KPI) ≥90% (P = 0, 012 and P = 0, 041) remained as independent prognostic factor for longer OS. All 4 prognostic scoring indices could be validated for OS assessment (BMV P = 0, 007; RPA P = 0, 026; GPA P = 0, 003; lung-mol GPA P = 0, 05).ConclusionIn this large cohort of NSCLC patients with BM treated with upfront and repeated SRS, OS was markedly favourable, in comparison to literature. Upfront SRS is an effective treatment approach in those patients and can decidedly reduce the impact of BM on overall prognosis. Furthermore, the analysed scores are useful prognostic tools for OS prediction.     

Neoadjuvant Gemcitabine-Cisplatin Plus Radical Cystectomy-Pelvic Lymph Node Dissection for Muscle-invasive Bladder Cancer: A 12-year Experience

IntroductionThe aim of this study was to determine drug delivery/toxicity, and pathologic/surgical outcomes of patients with muscle-invasive bladder cancer (MIBC) receiving neoadjuvant gemcitabine-cisplatin (GC) plus radical cystectomy-pelvic lymph node dissection (RC-PLND).Patients and MethodsChemotherapy and surgical/pathologic outcomes were retrospectively analyzed with 5-year survival follow-up at a referral center. Post-neoadjuvant chemotherapy (NAC) pathologic endpoints included complete response (pT0N0), residual non-MIBC (pTa/Tis/T1N0), and ≥ MIBC (≥ pT2 and/or N+). Associations of pathologic/surgical findings with overall survival (OS), disease-free survival (DFS), and surgical management with RC-PLND were analyzed (Cox regression).ResultsClinical T2a-T4aN0M0 MIBC patients (n = 154) from January 2000-October 2012 received GC plus RC-PLND. Patients (n = 117; 76%) received GC × 4 and 136 (88%) GC × 3. Five-year OS was 61% (95% confidence interval [CI], 53-71). Median number of resected lymph nodes (LNs) was 19. Down-staging was observed as follows: pT0N0: 21%; pTa/Tis/T1N0: 25%, with similar 5-year OS (85% and 89%, respectively). Five-year OS for < pT2 versus ≥ pT2 residual disease was 87% (95% CI, 78%-98%) versus 38% (95% CI, 27%-53%); P < .001. Post-NAC stage ≥ pT2 (HR, 6.79; 95% CI, 2.63-17.53; P < .001), positive LN (HR, 3.64; 95% CI, 1.84-7.19; P < .001), and positive margins (HR, 4.15; 95% CI, 1.68-10.25; P = .002) were associated with increased risk of all-cause death (multivariable analysis). An HR of 0.97 (95% CI, 0.94-1.00) was observed for each additional node removed, but this effect was not statistically significant (P = .056).ConclusionsNeoadjuvant GC achieves meaningful pathologic responses. Patients with ≥ pT2 residual disease, positive margins, or positive LN post-chemotherapy have inferior survival.     

Decitabine Versus Intensive Chemotherapy for Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia

BackgroundElderly patients with acute myeloid leukemia (AML) have generally had a poor prognosis with unfavorable clinical and biologic disease features. Hypomethylating agents have shown potential for treating medically unfit and elderly patients with AML.Patients and MethodsWe compared the outcomes of elderly patients with AML treated with decitabine and intensive chemotherapy (IC).ResultsThe data from 107 patients with newly diagnosed AML aged ≥ 65 years were analyzed. The overall response rate was 38.6% and was significantly greater in the IC group than in the decitabine group (65.6% vs. 26.1%; P < .001). With a median follow-up duration of survivors of 14.8 months, the median overall survival (OS) and event-free survival were 12.3 months (95% confidence interval [CI], 10.0-14.7) and 2.0 months (95% CI, 2.0-2.0), respectively, which were not different between the 2 treatment groups. The FLT3-internal tandem duplication mutation (hazard ratio [HR], 2.637; 95% CI, 1.379-5.043; P = .003), complex karyotype (HR, 2.513; 95% CI, 1.258-5.020; P = .009), and peripheral blood blast percentage at diagnosis (HR, 1.983; 95% CI, 1.148-3.422; P = .014) were analyzed as independent prognostic factors for OS. A subgroup analysis for OS showed that IC was superior to decitabine for patients with the FLT3-internal tandem duplication mutation (P = .025) and poor risk cytogenetics, except for −7/del(7q) (P = .005), and decitabine was associated with longer OS for patients with −7/del(7q) (P = .077).ConclusionDecitabine showed a similar OS to IC, despite the lower response rate in patients. The clinical outcomes of specific subgroups seemed to differ with different treatment options. Optimal therapeutic approaches for elderly patients with AML should be further examined.     

Multifocality and multicentricity in breast cancer and survival outcomes

BackgroundThe clinicopathological characteristics and the prognostic significance of multifocal (MF) and multicentric (MC) breast cancers are not well established.Patients and MethodsMF and MC were defined as more than one lesion in the same quadrant or in separate quadrants, respectively. The Kaplan–Meier product limit was used to calculate recurrence-free survival (RFS), breast cancer-specific survival (BCSS), and overall survival (OS). Cox proportional hazards models were fit to determine independent associations of MF/MC disease with survival outcomes.ResultsOf 3924 patients, 942 (24%) had MF (n = 695) or MC (n = 247) disease. MF/MC disease was associated with higher T stages (T2: 26% versus 21.6%; T3: 7.4% versus 2.3%, P < 0.001), grade 3 disease (44% versus 38.2%, P < 0.001), lymphovascular invasion (26.2% versus 19.3%, P < 0.001), and lymph node metastases (43.1% versus 27.3%, P < 0.001). MC, but not MF, breast cancers were associated with a worse 5-year RFS (90% versus 95%, P = 0.02) and BCSS (95% versus 97%, P = 0.01). Multivariate analysis shows that MF or MC did not have an independent impact on RFS, BCSS, or OS.ConclusionsMF/MC breast cancers were associated with poor prognostic factors, but were not independent predictors of worse survival outcomes. Our findings support the current TNM staging system of using the diameter of the largest lesion to assign T stage.     

MET Amplification (MET/CEP7 Ratio ≥ 1.8) Is an Independent Poor Prognostic Marker in Patients With Treatment-naive Non–Small-cell Lung Cancer

IntroductionThe MET pathway is a promising target in patients with non–small-cell lung cancer (NSCLC). Fluorescence in situ hybridization analysis has become a standard method to detect MET amplification. However, no consensus has been reached regarding the definition of MET amplification. We aimed to find clinically meaningful cutoffs for MET amplification that could be used as a prognostic marker and/or indication for MET inhibitor therapy.Patients and MethodsWe reviewed the fluorescence in situ hybridization results of MET/CEP7 (centromere of chromosome 7) for 2260 patients with treatment-naive NSCLC from 2014 to 2019. Clinical and pathologic data were collected from the medical records. Log-rank tests and Cox proportional hazard models were used to estimate the overall survival (OS) among patients with different MET/CEP7 ratios and/or MET copy numbers.ResultsOf the 2260 patients, 130 (5.8%) had had a MET/CEP7 ratio of ≥ 1.8 and 13 (0.6%) had had a ratio of ≥ 5.0. Of these 130 patients with a MET/CEP7 ratio of ≥ 1.8, 123 (95%) also had a MET copy number of ≥ 5. In general, a higher MET copy number and higher MET/CEP7 ratio were associated with advanced tumor stage. The OS was significantly shorter when the MET copy number was ≥ 10 and/or when the MET/CEP7 ratio was ≥ 1.8. A MET/CEP7 ratio of ≥ 1.8 remained a significant hazard to OS on multivariate analysis (hazard ratio, 1.63; P = .019).ConclusionsPatients with a MET copy number of ≥ 10 and/or MET/CEP7 ratio of ≥ 1.8 showed significantly poorer survival, and a MET/CEP7 ratio of ≥ 1.8 was an independent poor prognostic factor.     

Prognostic Variables Associated With Improved Outcomes in Patients With Stage III NSCLC Treated With Chemoradiation Followed by Consolidation Pembrolizumab: A Subset Analysis of a Phase II Study From the Hoosier Cancer Research Network LUN 14-179

IntroductionThe Hoosier Cancer Research Network (HCRN) LUN 14-179 is a phase II trial of consolidation pembrolizumab after concurrent chemoradiation for the treatment of patients with stage III non–small-cell lung cancer (NSCLC). Time to metastatic disease or death (TMDD), progression-free survival (PFS), and overall survival (OS) appear to be superior to that in historical controls of chemoradiation alone. Unfortunately, not all patients benefit from consolidation immunotherapy. We performed a univariate analysis to evaluate variables associated with PFS, metastatic disease, and OS.Patients and MethodsWe conducted a retrospective analysis of patients enrolled in HCRN LUN 14-179. Data collected included age, sex, stage, smoking status, programmed death ligand 1 status, Grade (G) ≥ 2 versus G ≤ 1 adverse event, G ≤ 2 versus G ≥ 3 pneumonitis, duration of pembrolizumab (< 4 vs. ≥ 4 cycles), chemotherapy regimen, performance status 0 versus 1, time to start pembrolizumab (4-6 vs. 6-8 weeks from radiation), volume of lung receiving at least 20 Gy of radiation (V₂₀; < 20% vs. ≥ 20%). Univariable Cox regression was performed to determine the variables associated with 3 end points: TMDD, PFS, and OS.ResultsFrom April 2015 to December 2016, 93 patients were enrolled and 92 were included in the efficacy analysis (1 patient was ineligible). For TMDD, improved outcomes might be associated (P < .1) with stage IIIA and ≥ 4 cycles of pembrolizumab. For PFS, improved outcomes (P < .1) might be seen for ≥ 4 cycles of pembrolizumab, stage IIIA and V₂₀ < 20%. For OS, improved outcomes (P < .1) might be seen for stage IIIA and ≥ 4 cycles of pembrolizumab.ConclusionStage IIIA and longer duration of pembrolizumab treatment might be associated with prolonged TMDD, PFS, and OS for patients with stage III NSCLC treated with chemoradiation followed by pembrolizumab.