Factors Associated With Upstaging of Melanoma Thickness on Final Excision.

INTRODUCTION: The incidence and risk factors associated with upstaging from initial biopsy to definitive excision in cutaneous melanoma have not been established. The aim of this study was to determine the incidence of tumor stage upstaging and associated risk factors using the National Cancer Database. METHODS: A retrospective study of the National Cancer Database between 2012 and 2016 was performed. The cohort of patients undergoing excision of melanoma with available data comprised 133,592 patients. Differences in characteristics for upstaging were determined using Wilcox rank-sum, chi-square, or Fisher's exact tests. Multivariable analysis was performed using logistic regression to determine factors associated with upstaging. RESULTS: Incidence of upstaging was 5.2%. Upstaged patients were older, male, of non-White race, and of lower education level (P < 0.001). Lesions of the head/neck and lower extremity had increased incidence of upstaging compared to the trunk (P < 0.001). Nodular and acral lentiginous melanoma was associated with higher incidence of upstaging compared to superficial spreading melanoma (P < 0.001). Patients with lymphovascular invasion had increased risk of upstaging (P < 0.001). CONCLUSIONS: Upstaging of melanoma is infrequent but is significantly more prevalent in non-White patients and those with lower educational status. Provider and patient education should include the higher risk of upstaging in these groups and the possible need for further surgical intervention, such as re-excision of margins and sentinel lymph node biopsy.

Burden and impact of multifactorial geriatric syndromes in allogeneic hematopoietic cell transplantation for older adults.

Multifactorial geriatric syndromes are highly prevalent in older patients with cancer. Because an increasing number of older patients undergo allogeneic hematopoietic stem cell transplantation (allo-HCT), we examined the incidence and impact of transplant-related geriatric syndromes using our institutional database and electronic medical records. We identified 527 patients age 60 years or older who had undergone first allo-HCT from 2001 to 2016 for hematologic malignancies. From the initiation of conditioning to 100 days posttransplant, new geriatric syndromes were predominantly delirium with a cumulative incidence of 21% (95% confidence interval [CI], 18%-25%) at day 100 followed by fall at 7% (95% CI, 5%-9%). In multivariable analyses of available pretransplant variables, fall within the last year, potentially inappropriate use of medication, thrombocytopenia, and reduced creatinine clearance were significantly associated with delirium; age older than 70 years and impaired activities of daily living were significantly associated with fall. In the 100-day landmark analysis, both delirium (hazard ratio [HR], 1.66; 95% CI, 1.09-2.52; P = .023) and fall (HR, 2.14; 95% CI, 1.16-3.95; P = .026) were significantly associated with increased nonrelapse mortality; moreover, fall (HR, 1.93; 95% CI, 1.18-3.14; P = .016), but not delirium, was significantly associated with reduced overall survival. Here, we establish baseline incidences and risk factors of common transplant-related geriatric syndromes. Importantly, we demonstrate significant associations of delirium and fall with inferior transplant outcomes. The burden and impact of transplant-related geriatric syndromes warrant the institution of patient-centered, preemptive, longitudinal, and multidisciplinary interventions to improve outcomes for older allo-HCT patients.

Allogeneic haematopoietic cell transplantation impacts on outcomes of mantle cell lymphoma with TP53 alterations.

TP53 alterations portend extremely poor prognosis in patients with mantle cell lymphoma treated with standard treatment modalities. We reviewed outcomes of 42 patients with available TP53 status who had received a reduced-intensity or non-myeloablative allogeneic haematopoietic cell transplant at our institution. We demonstrated a 2-year overall survival and progression-free survival of 78% [95% confidence interval (CI) 60-88] and 61% (95% CI 43-75), respectively. The 2-year cumulative incidences of relapse and non-relapse mortality were 19% and 20%, respectively. Importantly, there is no significant difference among patients with and without TP53 alterations, suggesting for the first time a beneficial treatment modality for these high-risk patients.

A Chemotherapy-Only Regimen of Busulfan, Melphalan, and Fludarabine, and Rabbit Antithymocyte Globulin Followed by Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplantations for the Treatment of Myeloid Malignancies.

We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplantations (HSCT) without the need for total body irradiation, thereby reducing toxicity while maintaining low rates of graft-versus-host disease (GVHD) and without increasing relapse. We investigated the myeloablative combination of busulfan (Bu) and melphalan (Mel), with the immunosuppressive agents fludarabine (Flu) and rabbit antithymocyte globulin (r-ATG) as cytoreduction before a TCD HSCT. No post-transplantation immunosuppression was administered. Between April 2001 and May 2008, 102 patients (median age, 55 years) with a diagnosis of primary or secondary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) underwent cytoreduction with Bu/Mel/Flu, followed by TCD grafts. TCD was accomplished by CD34+-selection followed by E-rosette depletion for peripheral blood stem cell grafts and, for bone marrow grafts, by soybean agglutination followed by E-rosette depletion. Donors included matched and mismatched, related and unrelated donors. Risk stratification was by American Society for Blood and Marrow Transplantation risk categorization for patients with primary disease. For patients with secondary/treatment-related MDS/AML, those in complete remission (CR) 1 or with refractory anemia were classified as intermediate risk, and all other patients were considered high risk. Neutrophil engraftment occurred at a median of 11 days in 100 of 101 evaluable patients. The cumulative incidences of grades II to IV acute and chronic GVHD at 1 year were 8.8% and 5.9%, respectively. Overall- and disease-free survival (DFS) rates at 5 years were 50.0% and 46.1%, respectively, and the cumulative incidences of relapse and treatment-related mortality were 23.5% and 28.4%, respectively. Stratification by risk group demonstrated superior DFS for low-risk patients (61.5% at 5 years) compared with intermediate- or high-risk (34.2% and 40.0%, respectively, P = .021). For patients with AML, those in CR1 had superior 5-year DFS compared with those in ≥CR2 (60% and 30.6%, respectively, P = .01), without a significant difference in incidence of relapse (17.1% and 30.6%, respectively, P = .209). There were no differences in DFS for other patient, donor, or disease characteristics. In summary, cytoreduction with Bu/Mel/Flu and r-ATG secured consistent engraftment of TCD transplantations. The incidences of acute/chronic GVHD and disease relapse were low, with favorable outcomes in this patient population with high-risk myeloid malignancies.

Second cancer risk in childhood cancer survivors treated with intensity-modulated radiation therapy (IMRT).

BACKGROUND: Treatment with radiotherapy (RT) is associated with an increased risk of second malignant neoplasms (SMNs) in childhood cancer survivors; it is unclear how treatment with intensity-modulated radiation therapy (IMRT) impacts this risk. We provide the first report of SMN risk in a cohort of childhood cancer survivors treated with IMRT. PROCEDURE: Retrospective review of patients ≤21 years of age treated with IMRT at Memorial Sloan Kettering Cancer Center between December 1998 and February 2009. Eligible patients survived at least 5 years from IMRT initiation. The risk of SMN was assessed via standardized incidence ratios (SIRs) and excess absolute risk (EAR). The cumulative incidence was estimated using methods for competing risks. RESULTS: Among 242 patients, six developed SMNs: four developed second solid cancers (all within the radiation field), and two developed myelodysplastic syndrome. Median time from IMRT initiation to a second solid cancer was 7.2 years (range, 6.8-9.5), with a 10-year cumulative incidence of 3.3% (95% confidence interval [CI], 1.0-7.8%), SIR of 11.4 (95% CI, 3.1-29.2) and EAR of 1.8 per 1,000 person-years (95% CI, -0.1 to 3.8). CONCLUSIONS: Longer follow-up is required to determine how the risk of SMN after IMRT compares to other modalities of radiation treatment, such as proton therapy. This study provides a preliminary report, which will serve as a baseline for future longitudinal analyses of SMN risk after IMRT. Pediatr Blood Cancer 2015;62:311-316. © 2014 Wiley Periodicals, Inc.