Background-Assessing calcium and vitamin D intake becomes important in conditions associated with low bone density such as anorexia nervosa (AN). Food records (FR) that assess intake over a representative time period are used in research and sometimes clinical settings. However, compliance in adolescents can be suboptimal.
Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). Yet, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC-amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with double hit lymphoma (DHL), all treated with either R-CHOP or intensive induction therapy. For SHL and MYC amp patients, the 2 year progression free survival rate (2yPFS) was 49% and 48% and 2 year overall survival rate (2yOS) was 59% and 71%, respectively. SHL patients receiving intensive induction experienced higher 2yPFS (59% vs. 23%, P=0.006) but similar 2yOS as compared with SHL patients receiving R-CHOP. SHL DLBCL patients treated with R-CHOP, but not intensive induction, experienced significantly lower 2yPFS and 2yOS (p<0.001 for both) when compared with MYC normal patients. SHL patients appear to have a poor prognosis, which may be improved with receipt of intensive induction.
The impact of race/ethnicity and the additional factors of age, sex, and socioeconomic status (SES) on follicular lymphoma (FL) outcomes have not been comprehensively studied and are not well defined. We examined population-based FL data from >18,000 patients in SEER-13 (1992-2009) investigating race/ethnicity and the impact of relevant factors including sex, age, and SES. Further, we compared data over two consecutive periods: Era-1 (1992-2000, n = 8,355) and Era-2 (2001-2009, n = 10,475). We identified 18,830 FL patients (White: n = 15,116; Hispanic: n = 1,627; Asian/Pacific Islander (A/PI): n = 1,002; and Black: n = 846). Median ages (years) differed significantly by race/ethnicity: White: 62.1, Hispanic: 57.3, A/PI: 60.7, and Black: 56.8 (P < 0.01 each race versus White). Overall survival (OS) was superior in Era-2 versus Era-1 for all patients (5-year: 76.7% versus 67.4%, respectively, P < 0.001). Further, survival was significantly improved for all age groups <80 years, for males (P = 0.0019), and females (P < 0.001) across eras. Females had superior OS compared with males in Era-1 (P = 0.004), but not in Era-2. Additionally, all races, except A/PI, had improved 5-year OS rates from Era-1 to Era-2. Finally, OS improved across eras for lower and higher SES populations; however those with higher SES were superior to lower SES patients in both eras. In conclusion, and in the largest comprehensive evaluation of US-based FL patients to date, we show that despite improvements in OS for FL over time, critical disparities across races/ethnicities, sex, and age groups remain in the modern era and warrant further studies.
Background:The mammalian target of rapamycin (mTOR) pathway is deregulated in castration-resistant prostate cancer (CRPC). We investigated the efficacy and toxicity of temsirolimus, an mTOR inhibitor, in chemotherapy-naïve CRPC.Methods:In this phase II open label study, eligible patients received IV temsirolimus at 25 mg weekly until objective disease progression, unacceptable toxicity or investigator's discretion. Toxicity was assessed every 4 weeks and responses every 8 weeks. Primary end point was calculating the overall response (OR) rate as well as measuring stable disease (SD) to assess the overall clinical benefit calculated as OR+SD. Secondary end points included prostatic-specific antigen (PSA) changes and time to progression biochemically and radiographically. Correlative studies included prospective assessment of quality of life (QoL) using two previously validated scales.Results:Although the sponsor halted the study early, 21 patients were enrolled of which, 15 were evaluable for efficacy and OR. Median age was 74 (range: 57–89), median PSA was 237.5 ng ml−1 (range: 8.2–2360), visceral disease present in 11 patients (52%), and 17 patients (81%) patients had Gleason score (7–10). Two patients had a partial response (PR) and eight had SD. The OR was 13% (2/15) and the overall clinical benefit (OR+SD) was 67% (10/15). Median time to radiographic disease progression was 2 months (range 2–10 months). Biochemical response assessment was available for 14/15 patients. Any PSA decline was observed in four patients (28.5% 4/14) with one patient (7%) having >50% PSA decline. Median time to progression by PSA was 2 months (range 1–10 months). With a median follow-up of 32 months, median overall survival (OS) was 13 months (range: 2–37) and three patients remain alive at the data cutoff (5/2013) for an OS of 14% at 4 years on an intent-to-treat analysis. Major non-haematologic toxicities included fatigue (19%) and pneumonia (14%). Main laboratory toxicities included hyperglycaemia (24%) and hypophosphatemia (14%). Also, 52% of enrolled patients had serious adverse events. Other toxicities were consistent with previously reported adverse events with temsirolimus. Despite these observed adverse events, temsirolimus did not adversely impact QoL.Conclusion:Temsirolimus monotherapy has minimal activity in chemotherapy-naïve CRPC.
Our data suggest that preservation of height potential in this cohort of girls with anorexia nervosa may be a consequence of delayed bone age. Hypogonadism may negate the deleterious effects of undernutrition on stature by allowing for a longer duration of growth.
Title: Disease Characteristics, Treatment Patterns, and Patient Outcomes of Lymphoplasmacytic Lymphoma or Waldenstroms Macroglobulinemia: A Single Institution Retrospective Review Introduction: Non-Hodgkin lymphomas (NHL) are a heterogeneous group of B-cell lymphoproliferative disorders, with certain subtypes progressing rapidly and requiring immediate treatment and others having a more indolent course. Lymphoplasmacytic lymphoma (LPL) or Waldenstroms macroglobulinemia (WM) is classified as an indolent lymphoma with a natural disease course involving multiple episodes of relapse and remission. Although a wide variety of acceptable treatment strategies exist in both the front line and relapsed settings, there are limited data for the clear recommendation of optimal treatment. We sought to determine if the choice of initial treatment of WM would have an effect on overall survival and cause of death. Methods: A retrospective chart review identified 52 patients diagnosed with LPL or WM between January 2006 and January 2016. Seven patients were excluded due to incomplete data, yielding a total of 45 patients over a 10-year period. Data regarding age, sex, comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status, IgM level at diagnosis, initial therapy, progression free survival, overall survival, and cause of death were collected. Patient demographics and treatment characteristics were calculated overall, and by three outcomes of interest: relapse free survival, treatment-related death, and all-cause mortality. Cox proportional hazard models adjusted for age, gender, and comorbidities were used to estimate the hazard ratios and 95% confidence intervals for events associated with initial therapy. Results: Of the 45 patients with WM, the average age of diagnosis was 66.9 (standard deviation: 12.3) and 23 patients (51.1%) were male. The majority of patients had an ECOG status of 2 or less at time of diagnosis (n=39, 86.7%). Thirty-five patients had data regarding IgM level at diagnosis, of which 15 (42.9%) were greater than 3000 mg/dl. The majority of patients (n=39, 86.7%) went on to receive treatment with chemotherapy. Among the patients who received treatment, 9 (23%) patients received rituximab therapy alone while 11 (28%) patients received fludarabine-based regimens. Twenty-four patients (61.5%) received rituximab as either monotherapy or as part of a chemotherapy combination while 14 (35.9%) did not receive rituximab at all. Fludarabine-based initial therapy was significantly protective against relapse (hazard ratio: 0.19, 95% CI: 0.04-0.87). Initial therapy that included rituximab was also protective of relapse, though not statistically significant (hazard ratio: 0.37, 95% CI: 0.13-1.10). At the conclusion of our review, 13 patients (29%) had died. Cause of death was considered treatment related in 3 of these patients: 2 patients developed myelodysplastic syndrome and 1 patient developed acute myeloid leukemia. All three patients had received fludarabine-based chemotherapy in the first line or subsequent setting. Conclusions: Our data suggest that fludarabine-based chemotherapy for initial management of LPL or WM resulted in improved progression free survival when compared to other chemotherapy regimens. We observed a trend toward improvement in progression free survival in patients that received chemotherapy that included rituximab. Interestingly, all patients that died of a treatment related myeloid toxicity had received fludarabine-based chemotherapy as an initial or as a subsequent therapy. We can conclude that while the use of fludarabine in treatment of LPL or WM results in a longer disease free interval, one should be cognizant of the risk of secondary hematologic malignancies. Rituximab or rituximab-based treatment for this low grade lymphoma remains a practical option. Disclosures No relevant conflicts of interest to declare.
165 Background: PTEN tumor suppressor gene is mutated in CRPC allowing for downstream protein activation including mammalian target of rapamycin (m TOR) leading to tumor cell growth and survival. We investigated TEM; an mTOR inhibitor, in chemotherapy-naïve CRPC patients (pts). Methods: Eligible pts received TEM at 25 mg weekly until disease progression. Responses were assessed every 8 weeks and toxicity every 4 weeks using CTCAE v.3. Quality of life (QOL) data were collected every cycle using two previously validated scales. Primary end point: Clinical Benefit (CB) [sum of complete response (CR), partial response (PR), and stable disease (SD)]. Secondary end points: Toxicity, time to next treatment (TTNT), time to radiographic and PSA progression (TTP and TTP-PSA respectively), impact on QOL, and overall survival (OS) Results: To date, 18 pts have been enrolled. Median age was 75 (57–89) with Gleason ≥7 in 14 (77%), and median PSA 211.3 (10.8-1,449). Ten pts (55.5%) had bone and visceral disease. Median time on androgen deprivation therapy (ADT) was 60 months (17–240). Previous therapy included: surgery 3, brachytherapy 3, external radiation 5, ADT 7. All pts were evaluable for toxicity and 16 for response. Six pts (33%) were taken off study without progression (2 withdrew, 3 persitsant thrombocytopenia, 1 non-compliance). Biochemical response data was available for 15 pts (2 not evaluable, 1 refused), of which 4 (26%) had PSA decline and 1 (6%) had >50% drop in PSA. TTP-PSA was 2 months (2-12). Sixteen pts were evaluable by RECIST; 2 PR and 9 SD for a CB of 69% (11 of 16). TTP or event (toxicity that took pts off study was an event) was 3 months (3–10) and TTNT was 4 months (2–11). With a median follow up of 18 months, 8 pts (44%) remain alive for a median OS of 13 months. Most commonly reported grade 3/4 toxicities: Thrombocytopenia (22%), hyperglycemia, hypophosphatemia, and fatigue (17% each), pneumonia and anemia (12% each). TEM did not impact QOL adversely without treatment-related mortality. Conclusions: TEM has activity in CRPC; some pts have CB without adverse impact on QOL. TEM should be further investigated in combination therapy in CRPC.
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