Go, Ronald S.

Purpose Data that guide selection of optimal local ablative therapy for the management localized hepatocellular carcinoma (HCC) are lacking. Because there are limited prospective comparative data for these treatment modalities, we aimed to compare the effectiveness of radiofrequency ablation (RFA) versus stereotactic body radiotherapy (SBRT) by using the National Cancer Database. Methods We conducted an observational study to compare the effectiveness of RFA versus SBRT in nonsurgically managed patients with stage I or II HCC. Overall survival was compared by using propensity score–weighted and propensity score–matched analyses based on patient-, facility-, and tumor-level characteristics. A sensitivity analysis was performed to evaluate the effect of severe fibrosis/cirrhosis. In addition, we performed exploratory analyses to determine the effectiveness of RFA and SBRT in clinically relevant patient subsets. Results Overall, 3,684 (92.6%) and 296 (7.4%) nonsurgically managed patients with stage I or II HCC received RFA or SBRT, respectively. After propensity matching, 5-year overall survival was 29.8% (95% CI, 24.5% to 35.3%) in the RFA group versus 19.3% (95% CI, 13.5% to 25.9%) in the SBRT group ( P < .001). Inverse probability–weighted analysis yielded similar results. The benefit of RFA was consistent across all subgroups examined and was robust to the effects of severe fibrosis/cirrhosis. Conclusion Our study suggests that treatment with RFA yields superior survival compared with SBRT for nonsurgically managed patients with stage I or II HCC. Even though our results are limited by the biases related to the retrospective study design, we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending local ablative therapy for localized unresectable HCC.

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is, in many ways, a unique hematologic entity. Unlike most hematologic conditions in which the diagnosis is intentional and credited to hematologists, the discovery of MGUS is most often incidental and made by nonhematologists. MGUS is considered an obligate precursor to several lymphoplasmacytic malignancies, including immunoglobulin light-chain amyloidosis, multiple myeloma, and Waldenström macroglobulinemia. Therefore, long-term follow-up is generally recommended. Despite its high prevalence, there is surprisingly limited evidence to inform best clinical practice both at the time of diagnosis and during follow-up. We present 7 vignettes to illustrate common clinical management questions that arise during the course of MGUS. Where evidence is present, we provide a concise summary of the literature and clear recommendations on management. Where evidence is lacking, we describe how we practice and provide a rationale for our approach. We also discuss the potential harms associated with MGUS diagnosis, a topic that is rarely, if ever, broached between patients and providers, or even considered in academic debate.

Purpose: Many cancer clinical trials lack appropriate representation of specific patient populations, limiting their generalizability. Therefore, we determined the representation of ethnic minorities and women in cancer clinical trials. Methods: Enrollment data from all therapeutic trials reported as completed in ClinicalTrials.gov from 2003 to 2016 were analyzed. We calculated enrollment fractions (EFs) for each group, defined as the number of enrollees divided by the 2013 Surveillance, Epidemiology, and End Results (SEER) database cancer prevalence. Results: Of 1,012 clinical trials, 310 (31%) reported ethnicity with a total of 55,689 enrollees. Participation varied significantly across ethnic groups. Non-Hispanic whites were more likely to be enrolled in clinical trials (EF, 1.2%) than African Americans (EF, 0.7%; P < .001) and Hispanics (EF, 0.4%; P < .001). A decrease in African American (6% v 9.2%) and Hispanic (2.6% v 3.1%) enrollment was observed when compared with historical data from 1996 to 2002. Younger patients (age younger than 65 years) were more likely to be enrolled in clinical trials than the elderly (64% v 36%; P < .001). Low recruitment of female patients was observed in clinical trials for melanoma (35%), lung cancer (39%), and pancreatic cancer (40%). Conclusion: We observed a decrease in recruitment of minorities over the past 14 years compared with historical data. African Americans, Hispanics, and women were less likely to be enrolled in cancer clinical trials. Future trials should take extra measures to recruit participants that adequately represent the US cancer population.

AbstractWaldenström macroglobulinemia (WM) is an immunoglobulin M‐associated lymphoma, with majority of cases demonstrating MYD88 locus alteration, most commonly, MYD88L265P. Owing to low prevalence of the wild‐type (WT) MYD88 genotype in WM, clinically relevant data in this patient population are sparse, with one study showing nearly a 10‐fold increased risk of mortality in this subgroup compared to patients with MYD88L265P mutation. We studied a large cohort of patients with MYD88L265P and MYD88WT WM, evaluated at Mayo Clinic, Rochester, between 1995 and 2016, to specifically assess the impact of these genotypes on clinical course. Of 557 patients, MYD88L265P mutation status, as determined by allele‐specific polymerase chain reaction, was known in 219, and 174 (79%) of those exhibited MYD88L265P, 157 of 174 patients had active disease. Of 45 (21%) patients with MYD88WT genotype, 44 had active disease. The estimated median follow‐up was 7.0 years; median overall survival was 10.2 years (95% CI: 8.4‐16.5) for MYD88L265P versus 13.9 years (95% CI: 6.4‐29.3) for the MYD88WT (P = 0.86). The time‐to‐next therapy from frontline treatment and the presenting features were similar in the two patient populations. For patients with smoldering WM at diagnosis, the median time‐to‐progression to active disease was 2.8 years (95% CI: 2.2‐3.8) in the MYD88L265P cohort and 1.9 years (95% CI: 0.7‐3.1) in the MYD88WT cohort (P = 0.21). The frequency of transformation to high‐grade lymphoma, or the development of therapy‐elated myelodysplastic syndrome was higher in the MYD88WT cohort (16% versus 4% in the MYD88L265P, P = 0.009). In conclusion, MYD88L265P mutation does not appear to be a determinant of outcome, and its presence may not be a disease‐defining feature in WM. Our findings warrant external validation, preferably through prospective studies.

AbstractExperience with intensive chemotherapy for relapsed/refractory multiple myeloma (RRMM) using VDT PACE regimen and its modifications (VDT PACE‐like regimens: VPLRs) outside TOTAL THERAPY trials is limited. We analyzed the outcomes of 141 patients with RRMM who received VPLRs at our center between 2006 and 2017 in an intent‐to‐treat analysis. Median age was 59.7 years and 66.7% of patients were male. A median of 2.2 years (range 0.02‐11.4) separated diagnosis of myeloma and inititation of VPLR. High‐risk cytogenetics were present in 52.4% patients. Patients received a median of 4 (range 1‐14) prior therapies, including stem cell transplant (SCT) in 66.7% patients. Ninety‐five (67.4%) patients received VDT PACE, 20 (14.2%) patients received VD PACE and 26 (18.4%) patients received other VPLRs. Patients received a median of 1 cycle (range 1‐9) of VPLR. We observed ≥ minimal response in 68.4%, ≥ partial response (PR) in 54.4% and ≥ very good PR in 10.3% patients. Median progression‐free survival was 3.1 months (95% CI, 1.9‐3.9) and median overall survival (OS) was 8.1 months (CI, 6.2‐9.9). One‐hundred and sixteen (82.3%) patients received some therapy after VPLR; 71 (61.2%) received systemic chemotherapy, while 45 (38.8%) underwent SCT. Median OS for those who received SCT after VPLR was 15.1 months (CI, 10.3‐20.8). Age ≥ 60 years (hazard ratio [HR] 2.3 [CI, 1.4‐3.7]; P = 0.0008) and R‐ISS III stage (HR‐ 2.4 [CI, 1.3‐4.0]; P = 0.003) predicted shorter OS in patients receiving VPLR. VPLRs are effective in heavily pre‐treated RRMM. In fit patients, SCT can be used to consolidate the response to VPLR.

AbstractAchievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10‐year period (2006‐2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1st reading of normal FLCr (hiFLC1; n = 166; 48.1%) were compared to those who did not (n = 179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi‐organ involvement (63.3 vs 46.4%; P = .002) and patients in advanced Mayo stage (42.9 vs 32.2%; P = .04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; P = .0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; P < .0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n = 111; 32.2%) versus not (n = 2234; 67.8%) showed consistent results [PFS; 27.1 (95%CI; 23, 53.8) vs 63.3 (95%CI; 55.4, 77) months; P < .0001 and OS; 78 (95% CI; 54.6, 98.8) vs NR (95%CI; NR, NR); P < .0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.

Abstract The epidemiology and outcomes of tumor lysis syndrome (TLS) are understudied. We used the National Inpatient Sample (NIS), a nationally representative weighted sample of all U.S. hospital discharges, to study outcomes and predictors of mortality in hospitalized patients with TLS. The NIS was queried for patients with a discharge diagnosis of TLS (ICD-9 code 277.88) from 2010–2013. Baseline characteristics and outcomes were analyzed. A multivariable logistic regression analysis was performed to identify predictors of mortality. From 2010–2013, 28,370 patients were discharged with a diagnosis of TLS. The most common malignancies were non-Hodgkin lymphoma (30%), solid tumors (20%), acute myeloid leukemia (19%), and acute lymphocytic leukemia (13%). Overall in-hospital mortality was 21%. The median length of stay was 10 days (IQR 5-22). Sixty-nine percent of patients experienced a severe complication, including sepsis (22%, 95% confidence interval [CI] 21–23), dialysis (15%, 95% CI 14–16), acute respiratory failure (23%, 95% CI 22–24), mechanical ventilation (16%, 95% CI 15–17), gastrointestinal hemorrhage (6%, 95% CI 5–7), cerebral hemorrhage (2%, 95% CI 2–3), seizures (1%, 95% CI 0.6–1), and cardiac arrest (2%, 95% CI 2–3). Predictors of mortality were derived from a multivariable logistic regression and included age, Elixhauser comorbidity score, insurance status, teaching versus nonteaching hospital, and cancer type. Predictors of increased length of stay included age, race, teaching versus nonteaching hospital, and cancer type. In the U.S., many patients with TLS develop life-threatening complications and a quarter die during hospitalization. As more cancer treatments become available, strategies to improve the supportive care of patients with TLS should be a priority.