Difference In OS Rate Research Articles

Short-term OS as a surrogate endpoint for 5-year OS in nasopharyngeal carcinoma in non-endemic area

PurposeTo address this evidence gap and validate short-term OS at less than 5 years as a reliable surrogate endpoint for 5-year OS.MethodsWe analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on non-metastatic NPC patients diagnosed between 2010 and 2015. Patients were categorized into radiotherapy and chemoradiotherapy groups.ResultsThis retrospective study examined 2,047 non-metastatic NPC patients. Among them, 217 received radiotherapy, and 1,830 received chemoradiotherapy. Our analysis results indicated that the 4-year OS may serve as a reliable surrogate endpoint for patients with AJCC clinical stage I (80 vs. 78%, P = 0.250), regardless of the treatment received. Specifically, in the radiotherapy group, patients with stage I, T0-T1, and N0 NPC showed similar OS rates at 4 and 5 years (83 vs. 82%, P = 1.000; 78 vs. 76%, P = 0.250; 78 vs. 77%, P = 0.500, respectively). Similarly, patients with stage II-IV, T2-T4, and N1-3 NPC showed no significant difference in OS rates between 3 and 5 years (57 vs. 51%, P = 0.063; 52 vs. 46%, P = 0.250; 54 vs. 46%, P = 0.125, respectively) in the radiotherapy group. In the chemoradiotherapy group, only the 3-year OS rate did not significantly differ from that at 5 years in stage I patients (79vs. 72%, P = 0.063).ConclusionsOur study suggests that short-term surrogate endpoints may be valuable for evaluating 5-year OS outcomes in NPC patients in non-endemic areas.

B-cell malignancies treated with targeted drugs and SARS-CoV-2 infection: A European Hematology Association Survey (EPICOVIDEHA).

Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs.

An Analysis from the WM UK Rory Morrison Registry: Waldenström's Macroglobulinaemia Patient Demographics, Disease Characteristics and Evolving Treatment Choices

Background Waldenström's macroglobulinaemia (WM) is a rare non-Hodgkin B cell lymphoma. Given its rarity, information about both patient demographics and disease characteristics are limited. Treatment is indicated for symptomatic patients and treatment regimens have evolved significantly in recent years. The Rory Morrison Registry (RMR) has comprehensive patient data available for analysis. We seek to draw conclusions about UK patient demographics and disease characteristics, and evaluate how treatment practices have evolved. Methods The RMR was searched for all patients with a diagnosis of WM. Patient demographics, disease characteristic, pathology results, treatment information and survival status retrieved. Kaplan Meier and log rank analysis was performed. Results 671 patients were identified from 19 different UK centres. Median age at diagnosis was 64 years (range 27-92, figure 1). Year of diagnosis ranged from 1978 to 2019, with 7 patients diagnosed &lt;1990, 31 1990-1999, 200 2000-2009, and 433 since 2010. Male to female ratio was 1.62:1. 90.4% were Caucasian, 5.9% Asian, 1.3% Afro-Caribbean, 0.7% mixed, and 1.6% of other ethnicity. Median haemoglobin at diagnosis was 112g/L (range 33-170), platelet count 242 (3-806), B2M 3 (range 0.2-56.3) and M-protein 17g/L (range 0-110.5). Median bone marrow infiltration was 40% (range 0-100%), with 35% lymphocytes and 5% plasma cell. MYD88 L265P mutations were detected in 160/190 patients (84.2%). CXCR4 mutations, for which testing is not widely available, were detected in 20/76 patients (26.3%). Peripheral neuropathy was seen in 74 patients, with 28 anti-MAG antibody positive. Other manifestations at diagnosis included cryoglobulinaemia (26), amyloidosis (12) and Schnitzler's syndrome (7). 2/317 patients were HIV positive, 4/341 HCV antibody positive, 27/334 HBSAb positive, and 12/327 HBCAb positive. IPSSWM score at diagnosis was available for 352 patients, with a low score in 122 (34.7%), intermediate score in 103 (29.3%), and high score in 123 (45%). 440 patients (65.6%) had received treatment, with a median time from diagnosis to treatment of two months (range 0-312). Indications for first line treatment initiation were: 35% paraprotein-related, 30% lymphoma-related , 2.1% B-symptoms, and a combination of indications for the remainder. Hyperviscosity was the treatment indication in 24.8% of patients, fatigue in 21.6% and peripheral neuropathy in 9.8%. At treatment commencement, 47% of patients had a haemoglobin of &lt;100g/L. CNS involvement was a feature in 1.5% and 1.5% high grade transformation (HGT). Lines of therapy received was one in 43.6%, two in 24.1%, three in 4.8%, four in 6.6% and ≥5 in 10.9%. In the past decade, 27.8% received DRC, 16.4% R-Bendamustine, 8.9% rituximab monotherapy, 7.7% R-CHOP and the rest varying combinations. 2.2% had received Bortezomib-containing therapy. Before 2010, chlorambucil (21.8%), R-CHOP (10.9%) and FC (9.3%) were the most frequently used first line treatments. BTK-inhibitors have become the most commonly used second line therapy, representing 23% of second line therapy after 2010, reflecting the availability of Ibrutinib on the Cancer Drugs Fund from 2017 and the availability of BTKi trials since 2015. 88 patients had received a BTKi at some point. 118 patients had deceased. Only 30 patients had a cause of death available; this included 7 patients who died from WM itself, 6 from pneumonia, 5 from sepsis (2 were neutropaenic), 3 from HGT, 2 from haemorrhage, 2 from thrombotic events, and 1 from CNS relapse. 5- and 10-year OS rates from diagnosis were 90.5% and 79.4%, with a significant difference in OS rates according to IPSSWM risk at diagnosis (p&lt;0.001, figure 2). There was a trend towards difference in OS rates (P=0.095) according to MYD88 status, with somewhat poorer OS rate amongst MYD88 wild-type patients. CXCR4-status did not impact the OS rate (p=0.93). Conclusions The median age at diagnosis was 64 years, with a third of patients diagnosed under the age of 60. Although diverse, the most frequent indications for treatment in this cohort are hyperviscosity, fatigue and peripheral neuropathy. OS rates are high and correlate with IPSSWM risk, but a majority of patients had received multiple lines of therapy reflecting the chronically relapsing nature of WM. Treatment practices are clearly evolving, with increasing first line use of DRC and R-Bendamustine, as well as BTK inhibitors for relapsed disease. Disclosures McCarthy: Janssen: Honoraria, Other: Educational grant to attend meetings . Pratt:Binding Site, Amgen, Takeda, Janssen, Gilead: Consultancy, Honoraria, Other: Travel support. D'Sa:Janssen: Honoraria, Research Funding.

Long-Term Results of Non- Fludarabine Versus Fludarabine-Based Conditioning Regimens in Severe Aplastic Anemia Patients

BACKGROUND AND OBJECTIVE: Allogenic hematopoietic cell transplantation (AHSCT) is the best therapeutic modality capable of correcting the hematologic manifestations of severe aplastic anemia (SAA), here in this study we have compared the results of well-tolerated fludarabine-based conditioning regimens for SAA patients who are heavily transfused undergoing AHSCT.DESIGN AND SETTINGS: This is a retrospective study consist of 25 patients diagnosed with SAA who underwent AHSCT between February 2002 and March 2015 at the Bone Marrow Transplantation Unit of Hacettepe University. All patients gave written informed consent for the procedure.PATIENTS AND METHODS: We analyzed the outcome of 25 SAA patients who had undergone AHSCT between 2002 and 2015. the median age at transplantation was 27(16-55) years. Patients received transplants from an HLA-identical sibling (n=24) and mismatched allogeneic related HSCT (n=1). Hematopoietic Stem Cells (HSC) were collected from the donors via apheresis. Eight patients underwent standard CY 50 mg/kg plus ATG-FreseniusR 5-10 mg/kg as conditioning fort he transplantation procedure and 13 patients conditioned with CY(50 mg/kg for 2 days) plus fludarabine 25 mg/m2 for 5 days and ATG-FreseniusR 5-10 mg/kg as AHSCT conditioning and received GvHD (Graft-vs-Host Disease) prophylaxis was standard CsA 3 mg/kg IV inf. plus Methotrexate(MTX) 10mg/m2 on day 1,and MTX 5 mg/m2 on days 3.,6. and 11.RESULTS: The median follow-up period for all the survivors was 117 months [minimum 3 and maximum 159 months]. The 5-year overall survival (os) for patients who did or did not receive fludarabine-based preparative regimens for the allograft was 93%, and 87%, respectively. However, there were no statistically significant differences in os rates between these two groups (P=0,58). Median neutrophil engraftment time was 11 days and median platelet engraftment time was 13 days. Primary graft failure occurred in 1 patients (4%) who received fludarabine-based conditioning regimens.CONCLUSION: Fludarabine-Based (Flu-CY-ATG) conditioning is a safe and viable option when compared to the standard CY-ATG conditioning in heavily-transfused SAA patients who undergo Allogeneic hematopoietic stem cell transplantation (allo-HSCT). DisclosuresNo relevant conflicts of interest to declare.

Ten-year follow-up of pentostatin combined with cyclophosphamide, and rituximab in previously untreated indolent B-cell lymphoma.

e19040 Background: Frontline regimens for indolent lymphoma are effective, but patients still suffer from relapse. From 2005 to 2007 we enrolled previously untreated patients on a phase II trial to investigate response rate and efficacy of pentostatin combined with cyclophosphamide and rituximab (PCR). PCR is an effective frontline therapy in chronic lymphocytic leukemia. We report the final analysis with a median follow up of nearly ten years. Methods: Patients were treated with 6 cycles of therapy with additional 3 cycles in case of not attaining a CR/CRu. All patients received Pentostatin (4 mg/m2), Cyclophosphamide (600 mg/m2), and Rituximab (375 mg/m2) on day one and every 21 days. Results: Of the 83 patients, five were considered unevaluable for response, but are included as non-responders in our intent-to-treat analysis. Diagnoses included FL (43.4%), SLL (38.5%), and MZL (18.1%). 78.3% had Ann Arbor stage IV lymphoma and 63.9% had bone marrow (BM) involvement. For all 83 patients, the overall response was 92%, and most toxicity events were hematologic, with grade ≥3 neutropenia in 68 of 509 cycles of chemotherapy administered. Long term toxicity includes secondary malignancies in 14 patients. Two patients developed treatment related MDS/AML and both occurred after additional lines of therapy. PFS at 10 years for FL, MZL, and SLL was 71%, 67% and 15%, respectively. PFS was affected by clinicopathologic characteristics. 10-year PFS rates for those with pretreatment β2M &lt; 2.2 and &gt; 2.2 mg/l were 71 % and 21 % respectively. Patients without BM involvement had 10-year PFS of 72% versus 29% for those with BM involvement. The median OS has not been reached. The overall survival rate was 87% at 5 years and 64% at 10 years. The difference in OS rate was statistically significant based on histology, 94% for FL, 66% for MZL, and 39 % for SLL. Conclusions: Long term follow up confirms that PCR is an effective, robust and tolerable treatment regimen for indolent B-cell lymphomas with 34 of 36 patients with FL alive at 10 years with 27 remaining in remission. Clinical Trial Information NCT00496873 Clinical trial information: NCT00496873.

Therapeutic efficacy of percutaneous microwave coagulation versus liver resection for single hepatocellular carcinoma ≤3 cm with Child-Pugh A cirrhosis

AimsThis study aimed to compare the therapeutic efficacy of liver resection (LR) and percutaneous microwave coagulation therapy (PMCT) for single hepatocellular carcinoma ≤3 cm (HCC) in cirrhotic livers. MethodsIn this study, 190 patients with single HCC ≤3 cm and Child-Pugh A cirrhosis were retrospectively reviewed. Among these patients, 122 patients underwent LR, and 68 patients received PMCT. The therapeutic efficacy and complications were compared between the two procedures. ResultsThere was no treatment-related hospital mortality in either group. Major complications were significantly more frequent in the LR group compared to the PMCT group (22.1% vs 5.9%, p = 0.004). The 1-, 3-, and 5-year OS rates for the LR group and PMCT group were 98.4%, 93.6%, 55.2% and 97.1%, 87.7%, 51%, respectively. There was no significant difference in OS rates between the LR group and PMCT group (p = 0.153). The 1-, 3-, and 5-year DFS rates were 96.7%, 70.5% and 43.7%, respectively, in the LR group, which were significantly higher compared to the PMCT group (92.6%, 50.5% and 26.3%, p = 0.006). Subgroup analyses revealed that HCC patients with portal hypertension (PH), OS and DFS were similar between the two groups. ConclusionsLR may provide better DFS and lower recurrence rates than PMCT for single HCC ≤3 cm and Child-Pugh A cirrhosis. For HCC patients with PH, PMCT may provide therapeutic effects that are similar to LR.

Chemoimmunotherapy With Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Bendamustine and Rituximab (BR) In Previously Untreated and Physically Fit Patients (pts) With Advanced Chronic Lymphocytic Leukemia (CLL): Results Of a Planned Interim Analysis Of The CLL10 Trial, An International, Randomized Study Of The German CLL Study Group (GCLLSG)

Chemoimmunotherapy With Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Bendamustine and Rituximab (BR) In Previously Untreated and Physically Fit Patients (pts) With Advanced Chronic Lymphocytic Leukemia (CLL): Results Of a Planned Interim Analysis Of The CLL10 Trial, An International, Randomized Study Of The German CLL Study Group (GCLLSG)

A phase II study of a temozolomide-based chemoradiotherapy regimen for high-risk low-grade gliomas: Preliminary results of RTOG 0424.

2008 Background: The primary endpoint of RTOG 0424 was to compare the 3-year survival (OS) of a regimen of concurrent and adjuvant temozolomide (TMZ) and radiotherapy (RT) in a high-risk low-grade glioma (LGG) population to the 3 year (yr) OS rate of the high risk EORTC LGG patients (pts) reported by Pignatti et al (J Clin Oncol 2002;20(8):2076-84). Secondary endpoints were: progression-free survival (PFS), toxicity, neurocognitive and quality of life data and molecular analysis. Methods: Pts with LGG's and &gt;=3 high risk factors (age&gt; = 40, astrocytoma dominant histology, tumor crossing midline, tumor &gt; = 6 cm or preoperative neurological function status &gt;1) were eligible and treated with conformal RT (54 Gy/30 fractions) plus concurrent TMZ 75 mg/m2 /day for 6 weeks and post-RT TMZ 150-200 mg/m2/day days 1-5 q28 days for up to 12 cycles. The study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months, and a 20% improvement in 3 yr OS rate from 54% to 65%, at a 10% significance level (1 sided) and 96% power. Results: Between January 2005-August 2009 136 pts were accrued, 129 (75 males, 54 females) were evaluable. Median age was 49 years, 91% had a Zubrod score 0-1 and 69%, 25% and 6% of pts had 3,4 and 5 high risk factors respectively. With a median follow-up time of 4.1 yrs, minimum follow-up of 3 yrs, MST has not yet been reached. Three year OS rate was 73.1% (95%CI:65.3-80.8%), significantly improved from historical control with a p-value &lt;0.0001. No difference in OS rates for pts with 3, 4 or 5 high risk factors was seen. 3 year PFS was 59.2% (95% CI:50.7-67.8%). Grade 3 adverse events (AE) occurred in 43% of pts and grade 4 AE in 10%, primarily hematologic, constitutional or gastrointestinal (nausea, anorexia) toxicity. One patient died of herpes encephalitis. Secondary analyses are ongoing. Radiation Quality Assurance was per protocol/ acceptable in 95% and 74% of pts completed chemotherapy per protocol. Conclusions: The 3 year OS rate of 73.1% for these high risk LGG pts is significantly higher than those reported for historical controls (54%, p &lt; 0.0001, one-sided) and the study-hypothesized 65%. Supported by RTOG U10 CA21661 and CCOP U10 CA37422 grants from NCI and Merck Clinical trial information: NCT00114140.