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Characterization of Second Primary Malignancies in Mucosa-Associated Lymphoid Tissue Lymphomas: A SEER Database Interrogation

Timilsina, Sunita; Damato, Aaron; Budhathoki, Nibash; Grossbard, Michael L; Braunstein, Marc
INTRODUCTION/BACKGROUND:Second primary malignancies (SPMs) are long-term complications in cancer survivors. Mucosa-associated lymphoid tissue (MALT) lymphomas are indolent extra-nodal marginal zone lymphomas, the majority of which typically have long-term survival. In this study, we investigated the incidence and pattern of SPMs in adult patients diagnosed with MALT lymphomas between January 2000 and December 2016. METHODS:Using the SEER-18 database and multiple primary standardized incidence ratio (MP-SIR) session of SEER stat software for statistical analysis, we assessed SPMs in MALT lymphomas. RESULTS:During this time, a total of 12,500 cases of MALT lymphomas were diagnosed, of which 1466 patients developed 1626 SPMs (O/E ratio: 1.48, 95% CI:1.41-1.55, P<.001). The median latency period for development of SPMs was 54 months (range 6-201 months). Secondary non-Hodgkin lymphomas, as defined by SEER as distinct from the primary lymphoma, was the most common SPM with 299 cases, followed by lung cancer (O/E ratio: 6.15, 95% CI:5.47-6.89, P<.0001). There were 898 SPMs that developed between 6- 59 months (O/E ratio: 1.47, 95% CI:1.37-1.57, P<.0001) and 728 after 60 months latency (O/E ratio: 1.5, 95% CI:1.39-1.61, P<.0001) after diagnosis of the primary MALT lymphomas. An increased incidence of both solid and hematologic cancers occurred in patients as early as 6 months after diagnosis of MALT lymphoma. CONCLUSION/CONCLUSIONS:These findings indicate that despite the indolent nature of most MALT lymphomas, there is an increased risk for SPMs warranting long-term follow up.
PMID: 34493476
ISSN: 2152-2669
CID: 5011962

Impaired Humoral Immunity to SARS-CoV-2 Vaccination in Non-Hodgkin Lymphoma and CLL Patients

Diefenbach, Catherine; Caro, Jessica; Koide, Akiko; Grossbard, Michael; Goldberg, Judith D; Raphael, Bruce; Hymes, Kenneth; Moskovits, Tibor; Kreditor, Maxim; Kaminetzky, David; Fleur-Lominy, Shella Saint; Choi, Jun; Thannickal, Sara A; Stapleford, Kenneth A; Koide, Shohei
Patients with hematologic malignancies are a high priority for SARS-CoV-2 vaccination, yet the benefit they will derive is uncertain. We investigated the humoral response to vaccination in 53 non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), or CLL patients. Peripheral blood was obtained 2 weeks after first vaccination and 6 weeks after second vaccination for antibody profiling using the multiplex bead-binding assay. Serum IgG, IgA, and IgM antibody levels to the spike specific receptor binding domain (RBD) were evaluated as a measure of response. Subsequently, antibody-positive serum were assayed for neutralization capacity against authentic SARS-CoV-2. Histology was 68% lymphoma and 32% CLL; groups were: patients receiving anti-CD20-based therapy (45%), monitored with disease (28%), receiving BTK inhibitors (19%), or chemotherapy (all HL) (8%). SARS-CoV-2 specific RBD IgG antibody response was decreased across all NHL and CLL groups: 25%, 73%, and 40%, respectively. Antibody IgG titers were significantly reduced (p < 0.001) for CD20 treated and targeted therapy patients, and (p = 0.003) for monitored patients. In 94% of patients evaluated after first and second vaccination, antibody titers did not significantly boost after second vaccination. Only 13% of CD20 treated and 13% of monitored patients generated neutralizing antibodies to SARS-CoV-2 with ICD50s 135 to 1767, and 445 and > 10240. This data has profound implications given the current guidance relaxing masking restrictions and for timing of vaccinations. Unless immunity is confirmed with laboratory testing, these patients should continue to mask, socially distance, and to avoid close contact with non-vaccinated individuals.
PMCID:8183024
PMID: 34100025
ISSN: n/a
CID: 4899722

Radiation Dose Reduction in Early-Stage Hodgkin Lymphoma

Shah, Bhartesh A; Oh, Cheongeun; Wu, S Peter; Karp, Jerome M; Grossbard, Michael; Gerber, Naamit K
INTRODUCTION/BACKGROUND:Treatment for early-stage Hodgkin lymphoma (HL) involves radiotherapy (RT), chemotherapy, or combined modality therapy (CMT). We analyzed reduction of RT dose in CMT, particularly in the context of German Hodgkin Study Group (GHSG) HD10 randomized trial results of 2010. PATIENTS AND METHODS/METHODS:The National Cancer Data Base was queried for patients with stage I-II HL receiving CMT. RT dose and associated characteristics were analyzed. Stage I and absence of B symptoms were used as a surrogate for early-stage favorable disease. RESULTS:Of 31,301 patients with stage I-II HL, 11,457 received CMT between 2004 and 2015. Using the surrogate defined above, 1955 patients (17.1%) were classified as having favorable disease. The majority (61.6%) received 30-36 Gy, while 7.0% received 20 Gy. The provision of 20 Gy was more common in stage I patients (12.3% vs. 5.4% in stage II) and at academic facilities (10.8% vs. 6.3%-8.9% at other facilities). Use of 20 Gy (vs. 30-36 Gy) was less likely with thorax site (odds ratio [OR] 0.43 vs. head and neck), stage II disease (OR 0.41), and B symptoms (OR 0.33). Notably, the use of 20 Gy increased dramatically after 2010 (the year of publication of GHSG HD10 trial results), with rates of 12.3% in 2010-2015 versus 0.1% in 2004-2009 (OR 6.3, P < .001). This was even more pronounced in cases of favorable early-stage disease, with 25.5% after 2010 versus 2.8% before 2010 (OR 13.2, P < .001). The use of doses > 36 Gy decreased over a corresponding time period (OR 0.44, P < .001). CONCLUSION/CONCLUSIONS:Analysis of CMT for patients with early-stage HL demonstrates variability in RT dose, including increasing use of 20 Gy and decreasing use of high doses > 36 Gy.
PMID: 32800712
ISSN: 2152-2669
CID: 4572982

Contribution of polypharmacy and potentially inappropriate medication use to inferior survival in older patients with aggressive lymphoma [Meeting Abstract]

Lin, R J; Guo, R; Becker, D J; Grossbard, M L; Magid, Diefenbach C S
Background: Survival outcomes for older patients with aggressive non-Hodgkin's lymphoma (NHL) are disproportionally inferior to those of younger patients. While differences in tumor biology may play a role, older patients are often frail with comorbidities, polypharmacy, and use potentially inappropriate medications (PIM).
Method(s): Using Cox proportional hazard and logistic regression models, we retrospectively analyzed all aggressive NHL patients age 60 and older diagnosed and treated at our institution from 2009-2014 to examine the effect of polypharmacy and PIM use on progression-free survival (PFS), overall survival (OS), and treatmentrelated toxicities.
Result(s): We included 141 patients with evaluable data after excluding patients with incomplete record. The median age was 71 years. At the time of diagnosis, 44% of patients used more than 4 medications and 47% used at least one PIM. During first-line treatment, only 43% of patients received chemotherapy of adequate relative dose intensity (>85% scheduled dose), and 63% experienced grade 3 or greater toxicities. Age, International Prognostic Index, and PIM use correlated with each other. Number of medications (p = 0.005) and PIM use (p < 0.001) were associated with shortened PFS by log-rank test, and PIM use remained a strong independent predictor of PFS in multivariable analysis (HR 1.84, p = 0.005). Number of medications (p = 0.003) and PIM use (p = 0.009) were also associated with shortened OS by log-rank test, although only albumin level predicted OS in multivariable analysis. Most importantly, PIM use was strongly associated with grade 3 or greater toxicities in multivariable analysis (OR 7.4, p = 0.001).
Conclusion(s): We report here for the first time adverse impacts of polypharmacy and PIM use in older patients with aggressive lymphoma. We suggest that drug-drug interactions may significantly impair the delivery of adequate chemotherapy dosage and increase toxicities thus resulting in inferior survival outcome. Our findings support the use of evidence-based geriatric and palliative care principles to guide meticulous medication management to eliminate outcome disparity in older lymphoma patients
EMBASE:630550137
ISSN: 1527-7755
CID: 4265362

Practice Patterns in Early Stage Hodgkin Lymphoma: Analysis of the National Cancer Database [Meeting Abstract]

Shah, B. A.; Wu, S. P. P.; Oh, C.; Yahalom, J.; Grossbard, M.; Gerber, N. K.
ISI:000485671501379
ISSN: 0360-3016
CID: 4111392

In Reply to Zhang [Letter]

Parikh, Rahul R; Grossbard, Michael L; Harrison, Louis B; Yahalom, Joachim
PMID: 28872005
ISSN: 1879-355x
CID: 2687732

Polypharmacy and potentially inappropriate medication use in older patients with aggressive non-Hodgkin lymphoma (NHL) leads to inferior survival and increased treatment-related toxicities [Meeting Abstract]

Lin, R J; Ma, H; Guo, R; Grossbard, M L; Troxel, A B; Diefenbach, C S M
Background: Survival outcomes for older patients with aggressive NHL are disproportionally inferior to those of younger patients. While differences in tumor biology may play a role, older patients are often frail with comorbidities, polypharmacy, and use potentially inappropriate medications (PIM) such as anticholinergics and benzodiazepines. Methods: Using Cox proportional hazard and logistic regression models, we analyzed all aggressive NHL patients age >= 60 treated at our two affiliated hospitals from 2009-2014 to examine the association of polypharmacy and PIM use with progression-free survival (PFS), overall survival (OS), and treatment-related toxicities. Results: In this updated and final analysis, we included 171 patients with complete records from these two hospitals. They share similar demographic, clinical, and laboratory characteristics except for higher International Prognostic Index (IPI) in patients from one hospital. The median age was 70 years (range 65-77). At the time of diagnosis, 46% of patients used more than 4 medications (polypharmacy) and 47% used at least one PIM. Only 43% of patients received first-line chemotherapy of adequate relative dose intensity (>85% dosage), and 65% experienced >= grade 3 toxicities. Polypharmacy and PIM use were associated with shortened PFS and OS by log-rank test. Most importantly, PIM use remained an independent predictor of PFS, OS, and >= grade 3 toxicities in multivariable analyses (Table). Conclusions: This is the first report of significantly adverse survival impacts of polypharmacy and PIM use in older patients with aggressive NHL, presumably from drug-drug interactions that increase toxicities and impair the delivery of adequate chemotherapy dosage. Our findings support the use of evidence-based geriatric principles to guide meticulous medication management to improve outcome disparity for these patients. (Table presented)
EMBASE:617435400
ISSN: 0732-183x
CID: 2651112

Survival of Asian Females With Advanced Lung Cancer in the Era of Tyrosine Kinase Inhibitor Therapy

Becker, Daniel J; Wisnivesky, Juan P; Grossbard, Michael L; Chachoua, Abraham; Camidge, D Ross; Levy, Benjamin P
INTRODUCTION: We examined the effect of access to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy on survival for Asian female (AF) EGFR mutation-enriched patients with advanced lung adenocarcinoma. MATERIALS AND METHODS: We used the Surveillance Epidemiology and End Results database to study patients with stage IV lung adenocarcinoma diagnosed from 1998 to 2012. We compared survival (lung cancer-specific survival [LCSS] and overall survival) between AFs and non-Asian males (NAMs), an EGFR mutation-enriched and EGFR mutation-unenriched population, respectively, with a diagnosis in the pre-EGFR TKI (1998-2004) and EGFR TKI (2005-2012) eras. We used Cox proportional hazards models to examine the interaction of access to TKI treatment and EGFR enrichment status. RESULTS: Among 3029 AF and 35,352 NAM patients, we found that LCSS was best for AFs with a diagnosis in the TKI era (median, 14 months), followed by AFs with a diagnosis in the pre-TKI era (median, 8 months), NAMs with a diagnosis in the TKI era (median, 5 months), and NAMs with a diagnosis in the pre-TKI era (median, 4 months; log-rank P < .0001). In a multivariable model, the effect of a diagnosis in the TKI era on survival was greater for AFs than for NAMs (LCSS, P = .0020; overall survival, P = .0007). A lung cancer diagnosis in the TKI era was associated with an overall mortality decrease of 26% for AFs (hazard ratio, 0.740; 95% confidence interval, 0.682-0.80) and 15.9% for NAMs (hazard ratio, 0.841; 95% confidence interval, 0.822-0.860). CONCLUSIONS: We found increased survival for lung adenocarcinoma diagnoses made after widespread access to EGFR TKIs, with the greatest increase among AF patients enriched for EGFR mutations. The present analysis eliminated the effect of crossover, which has complicated assessments of the survival advantage in EGFR TKI randomized trials.
PMID: 28029530
ISSN: 1938-0690
CID: 2383632

Hodgkin lymphoma patients demonstrate evidence of chronic activation/exhaustion in circulating T cell subsets [Meeting Abstract]

Diefenbach, Catherine S; Raphael, Bruce; Hymes, Kenneth; Grossbard, Michael; Moskovits, Tibor; Kaminetzky, David; Mcshea, Meghan; Martin, Peter; Ruan, Jia; Kozhaya, Lina; Bonakdar, Maryann; Abidoglu, Cem; Leonard, John; Unutmaz, Derya
ISI:000389941702187
ISSN: 1538-7445
CID: 2411312

Impact of Delays in Definitive Treatment on Overall Survival: A National Cancer Database Study of Patients with Hodgkin Lymphoma

Parikh, Rahul R; Grossbard, Michael L; Harrison, Louis B; Yahalom, Joachim
The purpose of this large observational study was to examine outcomes in Hodgkin lymphoma(HL) patients by timing to definitive chemotherapy(TTC) using standard and propensity score (PS)-adjusted Cox proportional hazards models. From 1998-2011, 56,457 patients with stage I-IV HL were studied, with a median follow-up of 6.0 years(median age=39). Median TTC was 26 days from diagnosis. The cohort of "early"(<60 days from diagnosis) TTC patients included 45,307(80.3%) patients and "late"(>/=60 days) TTC was 11,150(19.7%). Patients were more likely to experience early TTC if they were younger age, advanced stage, with "B" symptoms, favorably insured, favorable socioeconomic status, and treated at comprehensive cancer center(all p<0.05). Ten-year overall survival for patients with early TTC was 73.2% versus 70.0% for those with late TTC(HR=0.87;95%CI,0.83-0.92,p<0.0001). After PS-matching for co-variates, early TTC was not associated with overall survival (HR=0.96;95%CI,0.85-1.08,p=0.51). This represents the only study to evaluate overall survival by time to definitive treatment for HL.
PMID: 26374099
ISSN: 1029-2403
CID: 1779242