Assessing Outcomes in Patients With Multiple Myeloma Postautologous Stem Cell Transplantation: Contrasting the Effects of Melphalan Dosages at 200 mg/m2 versus 140 mg/m2.

BACKGROUND: No standard criteria for dose reduction exists for high-dose melphalan for autologous stem cell transplantation (ASCT) for multiple myeloma (MM) due to limited and conflicting evidence. OBJECTIVE: To evaluate efficacy and safety of standard dose (200 mg/m2 = Mel200) versus reduced dose 140 mg/m2 = Mel140) of melphalan in patients with MM undergoing ASCT. DESIGN: A single-center retrospective review of adults with MM for their first ASCT between January 1, 2010, and November 1, 2022, who received Mel200 or Mel140 as conditioning. Primary endpoint was progression-free survival (PFS). Secondary safety and efficacy endpoints included overall survival (OS), incidence of febrile neutropenia and acute kidney injury, and time to engraftment. Subgroup analyses were performed based on patient age and renal function. RESULTS: A total of 322 patients were included in the study, 240 in the Mel200 group and 82 in the Mel140 group. Baseline demographics were similar except patients receiving Mel140 were on average older and had worse kidney function. PFS at 2 years was not different between groups (P = .2335). No difference existed in 2 year PFS or OS for patients < 65 years of age versus ≥ 65 years of age or for patients with CrCl 30-59 mL/min versus CrCl ≥ 60 mL/min within either Mel200 group or Mel140 group (all P > .05). No differences existed between groups across all secondary outcomes. CONCLUSION: Reduced doses melphalan showed no differences in safety or efficacy outcomes versus standard dose even when analyzed based on age and renal function. Larger randomized controlled trials need to be performed to validate these findings.

Equity in oncology care: addressing disparities in cancer treatment in Georgia.

This research delves into the disparities in access to oncology care among cancer patients in Georgia, with a specific focus on the distinct challenges faced by African American (AA) individuals compared to non-African American (Non-AA) counterparts. Leveraging data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS) survey and supplementary online resources, the study meticulously examines socioeconomic factors, including income, education, and insurance coverage, which significantly influence the quality of cancer care received. The analysis reveals substantial income gaps between AA and Non-AA patients, underscoring the critical implications for healthcare access. Moreover, AA patients exhibit lower rates of full insurance coverage for cancer-related treatments, posing additional barriers to comprehensive care. By investigating the intersections of race, income, and education, the research aims to pinpoint the root causes of these disparities and proposes evidence-based solutions to address the identified challenges. The ultimate objective is to contribute valuable insights that inform targeted policy recommendations and community-based interventions, fostering a more equitable landscape for oncology care in Georgia. This study seeks to amplify awareness and advocate for tangible measures, striving toward healthcare equity for all cancer patients, irrespective of their racial or socioeconomic backgrounds.

A Push to Consider Mantle Cell Lymphoma in Adults with Leukemia/Lymphoma with Blastoid Morphology.

Mantle cell lymphoma (MCL) is an intermediate-grade B-cell lymphoma, representing 2.8% of all non-Hodgkin lymphomas in the US. It is associated with t(11;14)(q13; q23), which leads to the overexpression of cyclin D1, consequently promoting cell proliferation. MCL usually expresses CD19, CD20, CD43, surface immunoglobulins, FMC7, BCL2, cyclin D1, CD5, and SOX11. Herein is a case of a 67-year-old male, referred to our facility with shortness of breath, anemia (hemoglobin of 5.3 g/dL), thrombocytopenia (12 × 109/L), and leukocytosis (283 × 109/L). A peripheral blood smear showed marked lymphocytosis with blastoid morphology. Morphologic examination of the bone marrow biopsy revealed a diffuse sheet of blastoid cells expressing CD20 and CD10, but without CD5 or cyclin D1. Given these features, a differential diagnosis of diffuse large B-cell lymphoma (DLBCL) with germinal center derivation, high-grade follicular lymphoma, and Burkitt lymphoma was considered, with the latter not favored due to morphology. Additional studies revealed positive SOX11, and fluorescence in situ hybridization (FISH) studies detected t(11;14). These additional studies supported diagnosis of the blastoid variant of MCL. In conclusion, we present a unique and challenging case of MCL without cyclin D1 or CD5, but with an expression of CD10 and SOX11, along with t(11;14). Pathologists should explicitly consider the blastoid variant of MCL when dealing with mature B-cell neoplasms with blastoid morphology in adults, and utilize a broad panel of ancillary studies, including FISH and SOX11.

Azacitidine Maintenance Therapy Post-Allogeneic Stem Cell Transplantation in Poor-Risk Acute Myeloid Leukemia.

OBJECTIVE/BACKGROUND: Allogeneic hematopoietic stem cell transplant (HSCT) is the potential curative modality for poor-risk acute myeloid leukemia (AML), relapse remains the main reason for transplant failure. Early-phase studies showed azacitidine is safe for post-transplant maintenance therapy in AML. METHODS: We performed a single institutional prospective cohort study to evaluate the benefit of azacitidine maintenance therapy following allogeneic HSCT in poor-risk AML. The main objective of this study is to generate a hypothesis aiming to optimize post-transplantation outcomes in poor-risk AML. Forty-nine adults with poor-risk AML who underwent allogeneic HSCT were evaluated in a nonrandomized prospective cohort fashion. Thirty-one participants received post-transplant azacitidine (32 mg/m2) on Days 1-5 for a 28-day treatment cycle beginning approximately 40 days after transplantation. The study was controlled using 18 matched individuals who were on a noninterventional surveillance protocol. RESULTS: The relapse rate was significantly higher in the control cohort (66.67%) versus (25.81%) in the azacitidine maintenance cohort ( p < .005). Time to relapse was significantly prolonged by azacitidine maintenance, not reached versus 4.1 months in the control arm ( p < .0001). In addition, median overall survival was lower in the control cohort at 7.6 versus 27.4 months in the interventional cohort ( p < .0001). At a median follow-up of 24 months, incidence of graft-versus-host disease (GVHD) did not differ between study groups ( p = .325). In both cohorts, minimal residual disease was correlated with higher hazard of relapse (95% confidence interval, 2.31-13.74; p < .001). CONCLUSION: We conclude that low dose azacitidine maintenance following allogeneic HSCT in poor-risk AML, decreased relapse rate, and increased both the time to relapse and overall survival without increased risk of GVHD.

Clinical Considerations for Immunoparesis in Multiple Myeloma.

Multiple myeloma is a relatively common clonal plasma cell disorder, comprising 17% of hematologic malignancies. One of the hallmark features of this disease is immunoparesis, which is characterized by the suppression of immunoglobulin polyclonality. Though not entirely elucidated, the mechanism behind this process can be attributed to the changes in the tumor microenvironment. All treating clinicians must consider potential complications related to immunoparesis in the management of multiple myeloma. Though not explicitly described in large data series, the increased risk of infection in multiple myeloma is likely, at least in part, due to immunoglobulin suppression. Additionally, the presence of immunoparesis serves as a prognostic factor, conveying poorer survival and a higher risk of relapse. Even in the era of novel agents, these findings are preserved, and immunoglobulin recovery also serves as a sign of improved outcome following autologous HSCT. Though not within the diagnostic criteria for multiple myeloma, the presence and degree of immunoparesis should be at diagnosis for prognostication, and immunoglobulin recovery should be tracked following myeloablative therapy and autologous HSCT.

Prognostic impact of natural killer cell recovery on minimal residual disease after autologous stem cell transplantation in multiple myeloma.

INTRODUCTION: Natural killer cells are a potent effector lymphocyte subset that can induce cytotoxicity without the need for antigen sensitization or presentation. NK cells are a tempting target -for immune therapy, monoclonal antibody, or genetic engineering-to enhance immune surveillance mechanisms against myeloma cells. MATERIALS AND METHODS: We hypothesized an association between natural killer cell recovery after autologous stem cell transplantation (ASCT) and disease outcomes in multiple myeloma patients. We concluded a prospective study that started enrolling patients in January 2020 to identify the association between absolute NK cell count two to three after ASCT and disease outcomes after autologous stem cell transplantation in multiple myeloma using univariate and multivariate analysis. RESULTS: Natural killer cell recovery was evaluated during the third month after ASCT, day +60 to +90 post-ASCT. Our patients had a mean NK cell count of 90.53, ranging from 14 to 282 Cell/µL (Std Dev 84.64 Cell/µL). The odds of having a minimal residual disease (MRD-positivity) among patients with partial remission before transplantation is four times higher than patients with very good partial response or better (95% confidence interval 0.45-35.79). Our patients were classified into two groups based on MRD status after ASCT, an MRD-negative group of eight participants and an MRD-positive group of seven participants. The mean absolute NK cell count was significantly higher in the MRD-negative cohort, 131.38 Cell/µL, versus 43.86 Cell/µL in the MRD-positive group (p = 0.049). CONCLUSION: We conclude that for multiple myeloma patients treated with ASCT, high absolute NK cell counts two to three months after ASCT is an independent predictor for MRD negativity.

Case report: Hyperosmolar hyperglycemic syndrome secondary to PEG-asparaginase-induced hypertriglyceridemia and pancreatitis.

Pegylated (PEG)-asparaginase is an established treatment for acute lymphoblastic leukemias that exhibits an antitumor effect by depleting asparagine, an amino acid essential for leukemia cell protein synthesis. Pancreatitis with hypertriglyceridemia is a well-established toxidrome associated with PEG-asparaginase. However, impaired pancreatic synthetic function and hormone release have rarely been reported as a result of PEG-asparaginase pancreatitis. In this report, we present a 22-year-old woman recently diagnosed with T-acute lymphoblastic leukemia (T-ALL), who presented to the hospital with progressive weakness, confusion, blurry vision, hallucinations, and abdominal pain after induction treatment with daunorubicin, vincristine, PEG-asparaginase, and dexamethasone following the AYA protocol. She was found to have hypertriglyceridemia, acute pancreatitis, and hyperosmolar hyperglycemic syndrome. While pancreatitis and hypertriglyceridemia are commonly reported side effects of PEG-asparaginase, HHS related to these conditions has been sparsely reported. Providers should maintain awareness of this association and consider routine serial glucose monitoring of patients receiving PEG-asparaginase.

Pain Management in Oncology Patients Amidst the Opioid Epidemic: How To Minimize Non-Medical Opioid Use.

The opioid epidemic continues to be a significant public health concern. On the surface, it appears difficult to understate the profound consequences and unnecessary loss of life at the hands of the opioid crisis throughout the 2010s. This reality should not dissuade rigorous attention toward those who have suffered unnecessarily due to an overreaching backlash toward the opioid crisis. Oncology patients have been significantly impacted on both ends of the opioid crisis. Like other populations, cancer patients were first affected during the initial surge of opioid availability, prescription, and use at the beginning of the crisis, where opioid abuse and overdose negatively impacted cancer patient populations at similar rates as the general population. Yet, cancer patients were perhaps even more heavily affected during secondary events after the initial crisis, as opioid restrictions and the stigmatization, undoubtedly beneficial in many spaces, of opioid use became prevalent across the American society. During this second period of the opioid crisis (loosely from 2013 to the present day after the Veterans Health Administration Opioid Safety Initiative started), restrictions on opioids have significantly decreased the use and access of opioids for cancer patients. Management of pain, in general, is a complex topic, and cancer pain is no exception. Cancer patients may experience pain related to the disease itself, its treatment, or other comorbidities. This review aims to clarify the impact of reducing opioid use on cancer patients over the past eight years. We summarize the challenges facing providers as they attempt to manage cancer-related pain. Additionally, we propose tools for best practices to reduce the unnecessary suffering of cancer patients and protect against the overuse and abuse of opioids.

Research Staff Perspectives on Cancer Clinical Trials and Barriers to Recruitment: A Qualitative Research.

Background Clinical trials are key elements of the processes that account for many of the recent advances in cancer care. Unfortunately, they are becoming more challenging to conduct. Furthermore, a large number of clinical trials in oncology close early due to poor accrual. To identify opportunities for continued improvement in clinical trial enrollment, we sought to identify the obstacles encountered by our clinical trial research staff in these activities. Methods This is a prospective qualitative study, using Grounded Theory Methodology that was concluded at Stephenson Cancer Center (SCC). SCC has been the lead accruer to National Cancer Institute-Lead Academic Participating Sites (NCI-LAPS) trials over the past three years, and in addition, fields investigator-initiated and industry-sponsored trials. We conducted a survey of our research staff including all research nurses and disease site coordinators who participate in recruitment, screening, consenting, data collection, and compliance for interventional clinical trials. We then performed a follow-up meeting with our research coordinators to clarify responses. The study objectives were to highlight common barriers to recruiting adult cancer patients, encountered by research coordinators from all disease sites and to propose effective solutions to identified barriers. Results We are reporting our results of investigating barriers to clinical trials enrollment from a new perspective. The most commonly reported obstacles for clinical trials enrollment from our research staff's perspective were categorized into five themes: clinical trials protocol, communication barriers and cultural beliefs, financial barriers, patients' comorbidities and performance status, and physicians' commitment. Conclusions Although assessing barriers encountered by clinical research staff is an infrequently used metric for improving clinical trial enrollment, it provides an important perspective in the field. Implementing interventions to improve clinical trial feasibility and accrual is critical to improving cancer care.

Is a higher boost dose of radiation necessary after breast-conserving therapy for patients with breast cancer with final close or positive margins?

To determine rates of loco-regional recurrence (LRR), distant failure and overall survival for patients with breast cancer treated with breast-conserving therapy (BCT) with a close or positive surgical margin (C/PM) treated with standard dose boost radiation compared with a higher boost of radiation. We retrospectively studied 1476 patients with T1-T3 invasive breast cancer treated with BCT between 1992 and 2009. Median age was 57 years. Patients were divided into three groups: Group I included 1197 patients (81 %) with negative margins who received a standard boost (median 60 Gy) total dose to the lumpectomy cavity; Group II included 116 patients (8 %) with C/PM who received a standard boost (median 60 Gy); and Group III included 163 patients (11 %) with C/PM who received a higher boost (median 68 Gy). Biological subtypes (e.g., ER, PR, HER2/neu) were available for 858 patients (58 %) and were also assessed for any relationship to LRR rate. The Kaplan-Meier, Cox-regression, and log-rank tests were used to estimate rates of LRR and the significance of risk factors. Median follow-up was 8.6 years. The overall 5- and 10-year cumulative incidences of LRR were 2.1 % (95 % CI 0.8-2.1 %) and 4.5 % (95 % CI 3.4-6.0 %), respectively. The 5- and 10-year cumulative incidences of LRR for Group I (negative margins + standard boost) were 1.9 and 4.4 %; for Group II (C/PM + standard boost) were 3.9 and 7.0 %; and for Group III (C/PM + higher boost) were 2.9 and 3.8 %, respectively. No statistically significant differences in LRR rates were found among the three groups (p = 0.4). Similar results were obtained for distant failure (p = 0.3) and overall survival (p = 0.4). On multivariate analysis, tumor grade (p = 0.03), systemic-therapy (p = 0.005), node positivity (p = 0.05), young age (p = 0.001), and biological subtype (p = 0.04) were statistically significantly associated with higher LRR. Higher boost dose and margin positivity were not significant. Our data suggest that the 10-year risk of local recurrence for patients with close or positive margins receiving a standard boost was 7 % compared to 3.8 % for those receiving a higher boost; however, this difference was not significant. A higher boost dose did not significantly improve local control, nor did margins impact LRR risk in our cohort of patients.

Deep inspiration breath-hold technique in left-sided breast cancer radiation therapy: Evaluating cardiac contact distance as a predictor of cardiac exposure for patient selection.

PURPOSE: The purpose of this study was to evaluate the efficacy of voluntary deep inspiration breath-hold (DIBH) over a free-breathing (FB) technique to minimize cardiac radiation exposure in radiation therapy of left-sided breast cancer. Also, to better select patients for DIBH, the correlation between cardiac contact distance (CCD) and cardiac dose was assessed. METHODS AND MATERIALS: Thirty-five patients with left-sided breast cancer underwent DIBH and FB planning computed tomography scans, and the 2 plans were compared. Dose-volume histograms were analyzed for heart, left anterior descending coronary artery (LAD), left ventricle (LV), and left lung. Axial CCDs and parasagittal CCDs (FB-CCDps) were measured on FB planning computed tomography scans. RESULTS: Dose to heart, LAD, LV, and left lung was significantly lower in DIBH plans than in FB by all metrics. When DIBH was compared with FB, mean dose (Dmean) for heart was 0.9 versus 2.5 Gy; for LAD, 4.0 versus 14.9 Gy; and for LV, 1.1 versus 3.9 Gy (P < .0001), respectively. Seventy-five percent of the patients had a dose reduction of ≥ 0.9 Gy in Dmean to heart, ≥ 3 Gy in Dmean to LAD, and ≥ 1.7 Gy in Dmean to LV. FB-CCDps was associated with an equivalent uniform dose to heart, LAD, and LV for both the DIBH and FB plans (P ≤ .01); FB axial CCD measures were not. CONCLUSIONS: DIBH is a simple and highly effective technique to reduce cardiac exposure without compromising target coverage. FB-CCDps is potentially a very good predictor for cardiac exposure: the longer the FB-CCDps, the higher the dose. Our findings suggest that at least 75% of patients with left-sided breast cancer might benefit from the DIBH technique in terms of potentially clinically relevant dose reduction to cardiac structures, and therefore, it should be instituted as routine clinical practice.

The impact of isolated tumor cells on loco-regional recurrence in breast cancer patients treated with breast-conserving treatment or mastectomy without post-mastectomy radiation therapy.

To compare the outcome of patients with invasive breast cancer, who had isolated tumor cells (ITC) in sentinel lymph nodes, pN0(i+), to patients with histologically negative nodes, pN0. We retrospectively studied 1,273 patients diagnosed with T1-T3 breast cancer from 1999 to 2009. Patients were divided into 2 populations: 807 patients treated with breast-conserving surgery (BCS) and radiotherapy (RT), 85(10.5 %) with pN0(i+) and 722(89.5 %) with pN0. And the other population had 466 patients treated with mastectomy without post-mastectomy radiation therapy (PMRT), 80(17.2 %) with pN0(i+),and 386(82.8 %)with pN0. All patients underwent sentinel node biopsy, and the presence of ITC was determined. Patients with axillary dissection only or neoadjuvant chemotherapy were excluded. Among the 1,273 patients studied; 87.3 % received adjuvant systemic therapy. Kaplan-Meier, Cox regression, and log-rank statistical tests were used. Median patient age was 55.7 years. Median follow-up was 69.5 months. The 5- and 10-year cumulative incidence of Loco-regional recurrence (LRR) for patients treated with BCS and RT was 1.6 and 3.5 % for 85 pN0(i+) patients, and 2.4 and 5 % for 722 pN0 patients, respectively. For patients treated with mastectomy without PMRT, 5- and 10-year LRR rates were 2.8 and 2.8 % for 80 pN0(i+) patients, and 1.8 and 3 % for 386 pN0 patients, respectively. There were no statistically significant differences in LRR (p = 0.9), distant recurrence (p = 0.3) ,and overall survival (p = 0.5) among all groups. On multivariate analysis, ITC were not associated with increased risk of LRR, distant recurrence and overall survival. Grade (p = 0.003) and systemic therapy (p = 0.02) were statistically significantly associated with risk of LRR. Sentinel node ITC have no significant impact on LRR, distant recurrence and overall survival in breast cancer patients. Additional treatments such as axillary dissection, chemotherapy, or regional radiation should not be given solely based on the presence of sentinel node ITC.

Clinical outcome of isolated locoregional recurrence in patients with breast cancer according to their primary local treatment.

INTRODUCTION: This study assessed the clinical outcome and prognostic factors in patients with breast cancer who presented with isolated locoregional recurrence (ILRR) as a first event. MATERIALS AND METHODS: Between 1970 and 2008, 2960 patients with pT1-2, N0-3, M0 primary invasive breast cancer had either breast-conserving therapy (BCT) using lumpectomy and radiation therapy (RT) (group A = 1849 patients) or mastectomy without RT (group B = 1111 patients). Out of groups A and B, 117 and 103 patients, respectively, developed ILRR as a first event. Those 220 patients served as the basis for this study. A multivariate analysis was performed to estimate the clinical outcome of both groups, taking into account clinically relevant variables for the primary tumor and ILRR. RESULTS: The median follow-up after ILRR was 83 months. The median disease-free interval (DFI) was 79 and 38 months for groups A and B, respectively. The overall survival (OS) for group A was 81% and 69% at 5 and 8 years, respectively. For group B, it was 61% and 46%, respectively. The distant metastasis-free survival (DMFS) for group A was 84% at 5 years and remained 84% at 8 years. The DMFS for group B was 60% at 5 years and 52% at 8 years. In multivariate analysis, initial local treatment (BCT vs. mastectomy without RT), pathologic T stage, locoregional recurrence site (local vs. regional), and DFI (≤ 4 years vs. > 4 years) were significant prognostic variables for both OS and DMFS. CONCLUSION: Patients with breast cancer who developed ILRR after BCT as their initial local treatment have better clinical outcome compared with those who had mastectomy without RT.

Risk of local failure in breast cancer patients with lobular carcinoma in situ at the final surgical margins: is re-excision necessary?

PURPOSE: To compare the outcome of patients with invasive breast cancer both with and without lobular carcinoma in situ (LCIS)-positive/close surgical margins after breast-conserving treatment. METHODS AND MATERIALS: We retrospectively studied 2358 patients with T1-T2 invasive breast cancer treated with lumpectomy and radiation therapy from January 1980 to December 2009. Median age was 57 years (range, 24-91 years). There were 82 patients (3.5%) with positive/close LCIS margins (<0.2 cm) and 2232 patients (95.7%) with negative margins. A total of 1789 patients (76%) had negative lymph nodes. Patients who received neoadjuvant chemotherapy were excluded. A total of 1783 patients (76%) received adjuvant systemic therapy. Multivariable analysis (MVA) was performed using Cox's proportional hazards model. RESULTS: The 5-year cumulative incidence of locoregional recurrence (LRR) was 3.2% (95% confidence interval [CI] 2.5%-4.1%) for the 2232 patients with LCIS-negative surgical margins (median follow-up 104 months) and 2.8% (95% CI 0.7%-10.8%) for the 82 patients with LCIS-positive/close surgical margins (median follow-up 90 months). This was not statistically significant (P=.5). On MVA, LCIS-positive margins after the final surgery were not associated with increased risk of LRR (hazard ratio [HR] 3.4, 95% CI 0.5-24.5, P=.2). Statistically significant prognostic variables on Cox's MVA for risk of LRR included systemic therapy (HR 0.5, 95% CI 0.33-0.75, P=.001), number of positive lymph nodes (HR 1.11, 95% CI 1.05-1.18, P=.001), menopausal status (HR 0.96, 95% CI 0.95-0.98, P=.001), and histopathologic grade (grade 3 vs grade 1/2) (HR 2.6, 95% CI 1.4-4.7, P=.003). CONCLUSION: Our results suggest that the presence of LCIS at the surgical margin after lumpectomy does not increase the risk of LRR or the final outcome. These findings suggest that re-excision or mastectomy in patients with LCIS-positive/close final surgical margins is unnecessary.