Aiming for the cure in myeloma: Putting our best foot forward.

Frontline therapy for multiple myeloma (MM) is evolving to include novel combinations that can achieve unprecedented deep response rates. Several treatment strategies exist, varying in induction regimen composition, use of transplant and or consolidation and maintenance. In this sea of different treatment permutations, the overarching theme is the powerful prognostic factors of disease risk and achievement of minimal residual disease (MRD) negativity. MM has significant inter-patient variability that requires treatment to be individualized. Risk-adapted and response-adapted strategies which are increasingly being explored to define the extent and duration of therapy, and eventually aim for functional curability. In addition, with T-cell redirection therapies rapidly revolutionizing myeloma treatments, the current standard of care for myeloma will change. This review analyzes the current relevant literature in upfront therapy for fit myeloma patients and provides suggestions for treatment approach while novel clinical trials are maturing.

Lenalidomide or bortezomib as maintenance treatment remedy the inferior impact of high-risk cytogenetic abnormalities in non-transplant patients with newly diagnosed multiple myeloma: a real-world multi-centered study in China.

Maintenance treatment is a pivotal part in the whole process management of multiple myeloma (MM), which further deepens response and improves survival. However, evidence of maintenance in non-transplant MM patients is inadequate in real-world practice. Here, we retrospectively analyzed the efficacy and survival of 375 non-transplant MM patients from 11 centers between 2010 and 2021 in north China. After a median of seven cycles of front-line regimens, there were 141, 79, and 155 patients receiving lenalidomide maintenance (L-MT), bortezomib maintenance (B-MT), or thalidomide maintenance (T-MT), respectively. Patients on L-MT and B-MT had significantly greater proportions of high-risk cytogenetic abnormalities (HRCAs) detected by fluorescence in situ hybridization (FISH), which was defined as 1q21 gain, 17p deletion, adverse immunoglobulin heavy chain (IgH) translocations. Although the progression-free survival (PFS) and overall survival (OS) were comparable among the three groups, L-MT and B-MT remedied the negative impact of HRCAs on survival (PFS of patients with HRCAs vs. patients without HRCAs: L-MT, 26.9 vs. 39.2 months, p=0.19; B-MT, 20.0 vs. 29.7 months, p=0.36; OS not reached in all groups). Patients with HRCAs in the T-MT group presented inferior clinical outcomes compared to standard-risk patients (PFS, 12.1 vs. 22.8 months, p=0.02, HR=1.8, 95% CI 1.0-3.4; OS, 54.9 months vs. NR, p<0.001, HR=3.2, 95% CI 1.5-7.0). Achieving complete response (CR) after induction therapy led to superior PFS compared to other degrees of response, regardless of maintenance medication. Furthermore, maintenance duration over 24 months correlated with favorable survival. Due to the large gap of transplant eligibility in China, optimizing maintenance therapy is important for non-transplant MM patients. In this real-world multi-centered study, our findings suggest that clinicians prefer to prescribe lenalidomide or bortezomib as maintenance therapy in high-risk settings, which are superior to thalidomide in non-transplant MM patients. Achievement of CR and maintenance duration over 2 years are positive factors that influence survival.

The relationship between disease activity and UDCA response criteria in primary biliary cholangitis: A cohort study.

BACKGROUND: Uncertainty exists about how best to identify primary biliary cholangitis (PBC) patients who would benefit from second-line therapy. Existing, purely clinical, ursodeoxycholic acid (UDCA) response criteria accept degrees of liver biochemistry abnormality in responding patients, emerging data, however, suggest that any degree of ongoing abnormality may, in fact, be associated with an increased risk of adverse outcomes. This cohort study explores the link between response status, the biology of high-risk disease and its implications for clinical practice. METHODS: Proteomics, exploring 19 markers previously identified as remaining elevated in PBC following UDCA therapy, were performed on 400 serum samples, from participants previously recruited to the UK-PBC Nested Cohort between 2014 and 2019. All participants had an established diagnosis of PBC and were taking therapeutic doses of UDCA for greater than 12 months. UDCA response status was assessed using Paris 1, Paris 2 and the POISE criteria, with additional analyses using normal liver blood tests stratified by bilirubin level. Statistical analysis using parametric t tests and 1-way ANOVA. FINDINGS: Disease markers were statistically significantly higher in UDCA non-responders than in responders for all the UDCA response criteria, suggesting a meaningful link between biochemical disease status and disease mechanism. For each of the criteria, however, marker levels were also statistically significantly higher in responders with ongoing liver function test abnormality compared to those who had normalised their liver biochemistry. IL-4RA, IL-18-R1, CXCL11, 9 and 10, CD163 and ACE2 were consistently elevated across all responder groups with ongoing LFT abnormality. No statistically significant differences occurred between markers in normal LFT groups stratified by bilirubin level. INTERPRETATION: This study provides evidence that any ongoing elevation in alkaline phosphatase levels in PBC after UDCA therapy is associated with some degree of ongoing disease activity. There was no difference in activity between patients with normal LFT when stratified by bilirubin. These findings suggest that if our goal is to completely control disease activity in PBC, then normalisation of alkaline phosphatase and bilirubin should be the treatment target. This would also simplify messaging around goals of therapy in PBC, benefiting both patients and clinicians. FUNDING: Funding by the UK Medical Research Council (Stratified Medicine Programme) and an independent research grant by Pfizer. The study funders played no role in the study design, data collection, data analyses, data interpretation or manuscript writing.

Nanocarrier-Based Delivery of SN22 as a Tocopheryl Oxamate Prodrug Achieves Rapid Tumor Regression and Extends Survival in High-Risk Neuroblastoma Models.

Despite the use of intensive multimodality therapy, the majority of high-risk neuroblastoma (NB) patients do not survive. Without significant improvements in delivery strategies, anticancer agents used as a first-line treatment for high-risk tumors often fail to provide clinically meaningful results in the settings of disseminated, recurrent, or refractory disease. By enhancing pharmacological selectivity, favorably shifting biodistribution, strengthening tumor cell killing potency, and overcoming drug resistance, nanocarrier-mediated delivery of topoisomerase I inhibitors of the camptothecin family has the potential to dramatically improve treatment efficacy and minimize side effects. In this study, a structurally enhanced camptothecin analog, SN22, reversibly coupled with a redox-silent tocol derivative (tocopheryl oxamate) to allow its optimally stable encapsulation and controlled release from PEGylated sub-100 nm nanoparticles (NP), exhibited strong NB cell growth inhibitory activity, translating into rapid regression and durably suppressed regrowth of orthotopic, MYCN-amplified NB tumors. The robust antitumor effects and markedly extended survival achieved in preclinical models recapitulating different phases of high-risk disease (at diagnosis vs. at relapse with an acquired loss of p53 function after intensive multiagent chemotherapy) demonstrate remarkable potential of SN22 delivered in the form of a hydrolytically cleavable superhydrophobic prodrug encapsulated in biodegradable nanocarriers as an experimental strategy for treating refractory solid tumors in high-risk cancer patients.

Role of radiotherapy for high risk localized prostate cancers.

Management of high-risk prostate cancers is still a subject of debate, because of the lack of randomized trial comparing surgery and radiotherapy. If external beam radiotherapy is proposed, it must be associated with a long-term androgen deprivation therapy, at least 18-months. Irradiation of pelvic lymph nodes seems to improve distant metastasis-free survival and is so indicated in most of the cases. Moderate hypofractionation is not validated for pelvic lymph nodes irradiation. A combination of external beam radiotherapy and brachytherapy improved biochemical control in randomized trials without impact on survival. But this combination has been evaluated in large retrospective studies and seems to improve specific and overall survivals. An integrated boost on the MRI-defined index lesion is another way of dose escalation and improved also biochemical control. Stereotactic radiotherapy is not a validated option at this moment. For each patient, according to the extension of the disease, age, comorbidities and also his willingness, the best approach must be chosen, ideally in multidisciplinary meeting.

Upfront identification of high-risk follicular lymphoma.

Follicular lymphoma (FL) is a common disease with clinically indolent behavior, and a long natural history for the majority of patients. Despite excellent therapeutic strategies currently available for FL, approximately 10%-20% of patients will experience early disease progression, defined as occurring within two years of diagnosis. These patients have poor outcomes, with overall survival at 5 years ranging between 37% and 50%. Much of the biology driving early progression and inferior survival is attributed to early transformation events; however, transformation alone does not account for all the observed clinical heterogeneity and survival differences among patients. Several clinical, genetic, and molecular alterations in FL have been discovered that help define subsets of patients at risk for multiply relapses and refractory disease, and are slowly making their way into risk calculators to be used in daily practice. Additionally, the role of functional imaging with PET scan, as well as circulating and cell free tumor DNA are being evaluated as tools to define high-risk subsets of patients with FL. This review seeks to provide an over view of current and evolving biomarkers that define high-risk FL at diagnosis. The goal is for these tools to assist clinicians in integrating these rapidly evolving prognosis models into clinical practice, in the hopes of risk-stratifying treatments and improving outcomes for patients.

Favorable Outcomes after Single Cord Blood Transplantation for Patients with High-Risk Hematologic Diseases: A Single-Institute Retrospective Analysis.

The donor selection algorithm for cord blood (CB) with regards to matched related and unrelated donors has not been fully investigated. To assess the potential of CB transplantation (CBT) in patients with hematologic malignancies, especially for high-risk patients, we performed a single-institute retrospective analysis and compared the clinical outcomes of CBT with those of HLA-matched sibling and unrelated donor transplantation. We included 394 patients aged 16 years and older with hematologic diseases who received their first allogeneic hematopoietic cell transplantation between 1990 and 2018 at Kyoto University Hospital. These included 394 recipients of single unrelated cord blood units (UCB, n = 108), HLA-matched sibling donors (MSDs, n = 143), or HLA-matched unrelated donors (MUDs, n = 143). There was no significant difference in relapse-free survival (RFS) between UCB, MSD, and MUD recipients (P = .975). However, we found a significant interaction between transplant year and CBT outcomes (P = .010), with significantly better outcomes observed in the more recent years. Furthermore, we found that CBT showed better RFS than matched donor transplantation (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.30 to 0.84). This impact was more prominent in high-risk patients (HR, 0.35; 95% CI, 0.16 to 0.77), with lower relapse rates (HR, 0.25; 95% CI, 0.11 to 0.54), and comparable non-relapse mortality (NRM) compared to matched donor transplantation. Extensive chronic graft-versus-host disease was less frequently observed in CBT (HR, 0.58; 95% CI, 0.26 to 1.28). CBT associated with favorable outcomes, particularly in high-risk patients, with good RFS and low relapse rates without an increase in NRM in the single-institute study. Although the findings should be externally validated, CBT might serve as a reasonable donor choice, particularly in high-risk patients.

Validation of International Working Group response criteria in higher-risk myelodysplastic syndromes: A report on behalf of the MDS Clinical Research Consortium.

The utility of the International Working Group (IWG) 2006 response criteria for myelodysplastic syndromes (MDS) as a surrogate endpoint for outcomes is unclear. We assessed the validity of the IWG 2006 response criteria in a large cohort of higher-risk MDS patients (pts) treated at centers from the MDS Clinical Research Consortium. The best overall response rate (ORR) by IWG 2006 criteria to first-line therapy among 597 evaluable pts was 38% and include complete response (CR) 16%, marrow CR (mCR) 2%, partial response (PR) 10%, hematological improvement (HI) 10%, stable disease (SD) 33%, and progressive disease (PD) 24%. CR was associated with a better overall survival (OS) compared to all other response groups (P < 0.001). Among 470 pts treated with hypomethylating agent (HMA) as first-line therapy, the overall Response Rate, defined as HI or better was 39%. The median OS from time of best response was 21 mo, 8 mo, 14 mo, 12 mo, 13 mo, and 8 mo for CR, mCR, PR, HI, SD, and PD, respectively (P < 0.001). We validated those results in a separate cohort of 539 higher-risk MDS pts treated at Moffitt Cancer Center who received first-line HMA therapy, particularly addressing the value of mCR and mCR+HI. mCR alone without HI, SD, and PD outcomes were inferior to CR, PR, mCR+HI, and HI. In conclusion, CR by IWG 2006 response criteria can be used as a surrogate endpoint for OS in higher-risk MDS pts. Any response associated with restoration of effective hematopoiesis is associated with better outcome.

Role of Allogeneic HCT as Postremission Therapy for Transplant-Eligible Adult Lymphoblastic Leukemia/Lymphoma After Frontline Hyper-CVAD.

BACKGROUND: Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with cytarabine and methotrexate (hyper-CVAD) is a commonly used regimen in adults with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). Adult patients fit for pediatric-inspired protocols have an excellent outcome with chemotherapy alone. However, it is unclear whether patients receiving hyper-CVAD should undergo allogeneic hematopoietic cell transplantation (HCT) as postremission therapy. Our aim was to examine the role of HCT at first complete remission (CR1) in adult ALL/LBL after hyper-CVAD. PATIENTS AND METHODS: Adult patients with newly diagnosed ALL/LBL receiving frontline hyper-CVAD from 2008 to 2018 were identified and records retrospectively extracted. RESULTS: A total of 85 patients were identified and included for further analysis. The median (range) age was 23 (14-68) years, and 56 (66%) were male. A total of 24 (28%) had adverse cytogenetics, and 48 (56%) had at least one risk factor. All patients received hyper-CVAD as induction; induction failure was seen in 10 (12%). A total of 38 patients continued the hyper-CVAD course, while the remaining 47 received HCT in CR1. Three-year event-free survival (EFS) and overall survival for the entire cohort were 51.4% and 61.6%, respectively. Median follow-up of alive patients was 39.9 (3.8-123.8) months. At multivariable analysis for EFS, induction failure was associated with worse outcome (hazard ratio [HR], 4.8; 95% confidence interval [CI] 1.7-13.7; P = .003), whereas HCT in CR1 improved outcome (HR, 0.42; 95% CI 0.18-0.97; P = .044). Furthermore, HCT in CR1 was the only prognostic factor for overall survival (HR, 0.3; 95% CI 0.11-0.85; P = .023). CONCLUSION: HCT at CR1 resulted in a favorable EFS and overall survival in ALL/LBL patients after hyper-CVAD frontline therapy. Given that hyper-CVAD is a widely used protocol for adult patients, further examination of this observation is warranted.

Bispecific Antibodies for Multiple Myeloma: A Review of Targets, Drugs, Clinical Trials, and Future Directions.

Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematological neoplasm in adults, comprising 1.8% of all cancers. With an annual incidence of ~30,770 cases in the United States, MM has a high mortality rate, leading to 12,770 deaths per year. MM is a genetically complex, highly heterogeneous malignancy, with significant inter- and intra-patient clonal variability. Recent years have witnessed dramatic improvements in the diagnostics, classification, and treatment of MM. However, patients with high-risk disease have not yet benefited from therapeutic advances. High-risk patients are often primary refractory to treatment or relapse early, ultimately resulting in progression toward aggressive end-stage MM, with associated extramedullary disease or plasma cell leukemia. Therefore, novel treatment modalities are needed to improve the outcomes of these patients. Bispecific antibodies (BsAbs) are immunotherapeutics that simultaneously target and thereby redirect effector immune cells to tumor cells. BsAbs have shown high efficacy in B cell malignancies, including refractory/relapsed acute lymphoblastic leukemia. Various BsAbs targeting MM-specific antigens such as B cell maturation antigen (BCMA), CD38, and CD138 are currently in pre-clinical and clinical development, with promising results. In this review, we outline these advances, focusing on BsAb drugs, their targets, and their potential to improve survival, especially for high-risk MM patients. In combination with current treatment strategies, BsAbs may pave the way toward a cure for MM.

African KhoeSan ancestry linked to high-risk prostate cancer.

BACKGROUNDS: Genetic diversity is greatest within Africa, in particular the KhoeSan click-speaking peoples of southern Africa. South African populations represent admixture fractions including differing degrees of African, African-KhoeSan and non-African genetic ancestries. Within the United States, African ancestry has been linked to prostate cancer presentation and mortality. Together with environmental contributions, genetics is a significant risk factor for high-risk prostate cancer, defined by a pathological Gleason score ≥ 8. METHODS: Using genotype array data merged with ancestry informative reference data, we investigate the contribution of African ancestral fractions to high-risk prostate cancer. Our study includes 152 South African men of African (Black) or African-admixed (Coloured) ancestries, in which 40% showed high-risk prostate cancer. RESULTS: Genetic fractions were determined for averaging an equal African to non-African genetic ancestral contribution in the Coloured; we found African ancestry to be linked to high-risk prostate cancer (P-value = 0.0477). Adjusting for age, the associated African ancestral fraction was driven by a significant KhoeSan over Bantu contribution, defined by Gleason score ≥ 8 (P-value = 0.02329) or prostate specific antigen levels ≥20 ng/ml (P-value = 0.03713). Additionally, we observed the mean overall KhoeSan contribution to be increased in Black patients with high-risk (11.8%) over low-risk (10.9%) disease. Linking for the first time KhoeSan ancestry to a common modern disease, namely high-risk prostate cancer, we tested in this small study the validity of using KhoeSan ancestry as a surrogate for identifying potential high-risk prostate cancer risk loci. As such, we identified four loci within chromosomal regions 2p11.2, 3p14, 8q23 and 22q13.2 (P-value = all age-adjusted < 0.01), two of which have previously been associated with high-risk prostate cancer. CONCLUSIONS: Our study suggests that ancient KhoeSan ancestry may be linked to common modern diseases, specifically those of late onset and therefore unlikely to have undergone exclusive selective pressure. As such we show within a uniquely admixed South African population a link between KhoeSan ancestry and high-risk prostate cancer, which may explain the 2-fold increase in presentation in Black South Africans compared with African Americans.

Evaluation of serum markers for gastric cancer and its precursor diseases among high incidence and mortality rate of gastric cancer area.

BACKGROUND: Mongolia has the highest mortality rate of gastric cancer. The early detection of cancer and down-staging screening for high risk patients are essential. Therefore, we aimed to validate serum markers for stratifying patients for further management. METHODS: Endoscopy and histological examination were performed to determine high risk and gastric cancer patients. Rapid urease test, culture and histological tests were performed to diagnose Helicobacter pylori infection. Serum pepsinogen (PG) I and II and anti-H. pylori IgG were measured by ELISA. Receiver Operating Characteristic analysis was used to extract the best cut-off point. RESULTS: Totally 752 non-cancer and 50 consecutive gastric cancer patients were involved. The corpus chronic gastritis (72%: 36/50 vs. 56.4%: 427/752), corpus atrophy (42.0%: 21/50 vs. 18.2%: 137/752) and intestinal metaplasia (IM) (64.0%: 32/50 vs. 21.5%: 162/752) were significantly higher in gastric cancer than non-cancer patients, respectively. Therefore, corpus chronic gastritis, corpus atrophy and IM were considered as high risk disease. The best serum marker to predict the high risk status was PGI/II < 3.1 (sensitivity 67.2%, specificity 61%) and PGI/II further reduced to < 2.2 (sensitivity 66%, specificity 65.1%) together with PGI < 28 ng/mL (sensitivity 70%, specificity 70%) were the best prediction for gastric cancer. The best cut-off point to diagnose H. pylori infection was anti-H. pylori IgG > 8 U/mL. Multivariate analysis showed that anti-H. pylori IgG > 8 U/mL and PGI/II < 3.1 increased risk for high risk status and PGI/II < 3.1 remained to increase risk for gastric cancer. CONCLUSION: The serum diagnosis using PGI/II < 3.1 cut-off value is valuable marker to predict high risk patients for population based massive screening.

Male Oncology Research and Education program for men at high risk for prostate cancer.

Three groups of men are at high risk of developing prostate cancer: men with a strong family history of prostate cancer, men of West African or Caribbean ancestry, and men with a germline pathogenic variant in a prostate cancer-associated gene. Despite the fact that those men constitute a significant portion of the male population in North America, few recommendations for prostate cancer screening specific to them have been developed. For men at general population risk for prostate cancer, screening based on prostate-specific antigen (psa) has remained controversial despite the abundance of literature on the topic. As a result, recommendations made by major screening authorities are inconsistent (ranging from no psa screening to baseline psa screening at age 45), allowing physicians to pick and choose how to screen their patients. The Male Oncology Research and Education (more) program is an observational research program that serves as an academic platform for multiple research foci. For its participants, serum and dna are biobanked, medical information is collected, and contact for relevant research-related opportunities is maintained. This research program is paired with a specialized clinic called the more clinic, where men at high risk are regularly screened for prostate cancer in a standard approach that includes physical examination and serum psa measurement. In this article, we describe the goals, participant accrual to date, and projects specific to this unique program.

Image-guided radiotherapy reduces the risk of under-dosing high-risk prostate cancer extra-capsular disease and improves biochemical control.

BACKGROUND: To determine if reduced dose delivery uncertainty is associated with daily image-guidance (IG) and Prostate Specific Antigen Relapse Free Survival (PRFS) in intensity-modulated radiotherapy (IMRT) of high-risk prostate cancer (PCa). METHODS: Planning data for consecutive PCa patients treated with IMRT (n = 67) and IG-IMRT (n = 35) was retrieved. Using computer simulations of setup errors, we estimated the patient-specific uncertainty in accumulated treatment dose distributions for the prostate and for posterolateral aspects of the gland that are at highest risk for extra-capsular disease. Multivariate Cox regression for PRFS considering Gleason score, T-stage, pre-treatment PSA, number of elevated clinical risk factors (T2c+, GS7+ and PSA10+), nomogram-predicted risk of extra-capsular disease (ECD), and dose metrics was performed. RESULTS: For IMRT vs. IG-IMRT, plan dosimetry values were similar, but simulations revealed uncertainty in delivered dose external to the prostate was significantly different, due to positioning uncertainties. A patient-specific interaction term of the risk of ECD and risk of low dose to the ECD (p = 0.005), and the number of elevated clinical risk factors (p = 0.008), correlate with reduced PRFS. CONCLUSIONS: Improvements in PSA outcomes for high-risk PCa using IG-IMRT vs. IMRT without IG may be due to improved dosimetry for ECD.

The EMPaCT Classifier: A Validated Tool to Predict Postoperative Prostate Cancer-related Death Using Competing-risk Analysis.

BACKGROUND: Accurate prediction of survival after radical prostatectomy (RP) is important for making decisions regarding multimodal therapies. There is a lack of tools to predict prostate cancer-related death (PCRD) in patients with high-risk features. OBJECTIVE: To develop and validate a prognostic model that predicts PCRD combining pathologic features and using competing-risks analysis. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective multi-institutional observational cohort study of 5876 patients affected by high-risk prostate cancer. Patients were treated using RP and pelvic lymph node dissection (PLND) in a multimodal setting, with median follow-up of 49 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For PCRD prediction, a multivariate model with correction for competing risks was constructed to evaluate pathologic high-risk features (pT3b-4, Gleason score ≥8, and pN1) as predictors of mortality. All possible associations of the predictors were combined, and then subgroups with similar risk of PCRD were collapsed to obtain a simplified model encoding subgroups with significantly differing risk. Eightfold cross-validation of the model was performed. RESULTS AND LIMITATIONS: After applying exclusion criteria, 2823 subjects were identified. pT3b-4, Gleason score ≥8, and pN1 were all independent predictors of PCRD. The simplified model included the following prognostic groups: good prognosis, pN0 with 0-1 additional predictors; intermediate prognosis, pN1 with 0-1 additional predictors; poor prognosis, any pN with two additional predictors. The cross-validation yielded excellent median model accuracy of 88%. The retrospective design and the short follow-up could limit our findings. CONCLUSIONS: We developed and validated a novel and easy-to-use prognostic instrument to predict PCRD after RP+PLND. This model may allow clinicians to correctly counsel patients regarding the intensity of follow-up and to tailor adjuvant treatments. PATIENT SUMMARY: Prediction of mortality after primary surgery for prostate cancer is important for subsequent treatment plans. We present an accurate postoperative model to predict cancer mortality after radical prostatectomy for high-risk prostate cancer.

National Trends and Predictors of Organ-sparing for Invasive Penile Tumors: Expanding the Therapeutic Window.

INTRODUCTION: The purpose of this study was to analyze contemporary trends and predictors in the use of organ-sparing treatment (OST) for low-stage invasive penile tumors as well as to ascertain its impact on overall mortality (OM) in those with high-risk (pT2) disease. PATIENTS AND METHODS: The National Cancer Data Base was queried for patients with clinically nonmetastatic penile cancer and available pathologic tumor (pT) and treatment data from 1998 to 2012. Independent predictors for performance of OST were analyzed. Multivariable Cox proportional hazard regression was used to identify factors of OM in a subset of patients with pT2 disease. RESULTS: A total of 4231 patients with ≤ pT2cN0cM0 primary penile cancer were identified over a median follow-up of 39.6 months. Approximately 49% of patients received OST over the study period (P = .009). Older age, Hispanic ethnicity, urban counties, academic facilities, and pT2 disease were negative predictors for OST (all P < .05), whereas grade and years of diagnosis where associated with increased performance (P < .01). In subgroup analysis of pT2 patients, older age, black race, comorbidity, node status, and grade were associated with higher OM (all P < .05). When compared with radical penectomy, partial penectomy was associated with decreased OM (hazard ratio, 0.67; 95% confidence interval, 0.52-0.87; P = .002), whereas organ-sparing did not affect survival (hazard ratio, 0.83; 95% confidence interval, 0.52-1.31; P = .419) in these patients. CONCLUSION: Ethnic and socioeconomic differences exist in the local management of penile tumors. No impact on OM was observed for those with high-risk cases treated with organ-sparing at intermediate follow-up. More studies are needed to evaluate oncologic efficacy of organ-sparing in carefully selected invasive penile tumors.

Plasma cell myeloma with dual expression of kappa and lambda light chains.

Plasma cell myeloma is a clonal proliferation of neoplastic plasma cells and typically expresses a monoclonal heavy and/or light chain immunoglobulin. Plasma cell myeloma with dual expression of kappa and lambda light chains in a single clone is extremely rare. Here we report three cases of plasma cell myeloma with a co-expression of both kappa and lambda light chains. All three cases were confirmed by comprehensive workup including IHC, ISH and flow cytometry analysis to detect light chain expression patterns at the mRNA and protein levels. We also reviewed three cases so far published in the literature. Our study suggests that plasma cell myeloma with dual light chain expression may be more likely to be light chain only myeloma. It may have a high frequency of complex cytogenetic and/or FISH abnormalities, associated with a high-risk disease.

Prostate cancer-specific death in brachytherapy treated high-risk patients stratified by pre-treatment PSA.

PURPOSE: To evaluate prostate-cancer specific mortality (PCSM) in a cohort of high-risk patients treated with a permanent prostate brachytherapy approach, stratified by pre-treatment PSA. MATERIAL AND METHODS: 448 high-risk patients (NCCN criteria) underwent permanent prostate brachytherapy. High risk patients were stratified by pre-treatment PSA (≤ 10.0, 10.1-20, and > 20 ng/ml). Biochemical failure (BF), prostate cancer-specific mortality (PCSM), distant failure (DM), and overall mortality (OM) were assessed as a function of prognostic group. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on outcome. RESULTS: The 10-year OM, BF, and PCSM for the entire cohort were 28.5%, 13.3%, and 4.9%, respectively. At 10 years, PCSM was 2.5%, 10.7%, and 4.5% in the PSA ≤ 10, 10.1-20, and > 20 ng/ml groups, respectively. No statistically significant differences in BF or overall survival (OS) were noted when stratified by pre-treatment PSA. DF was the most common in the 10.1-20 ng/ml cohort (8.6% at 10 years). In multivariate analysis, PCSM was most closely related to percent positive biopsies (p = 0.001) and tobacco (p = 0.042). CONCLUSIONS: High-risk prostate cancer treated with permanent prostate brachytherapy and supplemental external beam radiotherapy resulted in excellent long-term biochemical control and PCSM. Overall, PCSM was low in all cohorts but highest in the intermediate PSA group (10.1-20 ng/ml).

Node-positive cutaneous squamous cell carcinoma of the head and neck: Survival, high-risk features, and adjuvant chemoradiotherapy outcomes.

BACKGROUND: Data lacks to guide treatment of regionally metastatic cutaneous head and neck squamous cell carcinoma (HNSCC). METHODS: We conducted a retrospective review of 80 patients treated for regionally metastatic cutaneous HNSCC. The effect of various clinicopathologic variables on overall survival (OS) was investigated, in addition to outcomes by treatment modality. RESULTS: On multivariate regression, cutaneous primary >2 cm (p = .03) and extracapsular spread (ECS; p = .01) were significantly associated with decreased OS. Location of regional metastasis (neck vs parotid vs both) had no effect on OS (p = .2), nor did the presence of a cutaneous primary at the time of presentation (p = .9). The 3-year survival was 43%, 52%, and 49% for surgery alone, adjuvant radiation, and adjuvant chemoradiation, respectively. Fifty-one percent of patients had a recurrence of their disease. CONCLUSION: Regionally metastatic cutaneous HNSCC is an aggressive disease associated with high recurrence rates. Patients with tumors >2 cm and ECS have poorer OS despite adjuvant therapy. © 2017 Wiley Periodicals, Inc. Head Neck 39: 881-885, 2017.