5-year Time To Progression Research Articles

Crebbp Mutations Are Associated with Shorter Time to Progression in Limited-Stage Follicular Lymphoma Treated with Radiation

Background: Limited-stage follicular lymphoma (FL), defined as stage I or II disease, is generally treated with radiation therapy (RT) to involved nodes with excellent overall response rates. However, nearly half of all limited-stage FL patients will ultimately experience a relapse. Most prior research on genetic prognostication in FL has focused on patients with advanced disease undergoing systemic therapy, however, there is evidence to suggest that there are genetic differences in limited versus advanced-stage FL, for example, in the frequency of KMT2D and BCL2 mutations as well as gene expression profiles. Objective: We hypothesized that genetic characterization of pre-treatment biopsies can identify those limited-stage FL patients that are at high risk of relapse following radiation therapy. Methods: Pre-treatment formalin-fixed and paraffin-embedded tissue block samples were obtained from adult patients with limited-stage FL, grade 1-3A, treated with curative-intent RT diagnosed between 1995-2018, from 6 international sites in Canada, Europe and Australia. Hybridization-based targeted sequencing of a 71 gene panel was performed, which included genes that are known to be recurrently mutated in FL. Samples with >50X mean on target coverage were retained in the analysis. Variant calling was performed using Mutect2. Germline polymorphisms were filtered out by cross-referencing with dbSNP and gnomAD databases. Only coding, non-silent mutations detected at a variant allele frequency greater than 0.1 were considered. Patient demographics and clinical data were examined retrospectively. Genes mutated at a proportion of 10% or more of the cohort were tested for association with time to progression (TTP) and overall survival (OS). Results: One hundred and seventeen pre-treatment samples from distinct patients were accrued. The median age was 58 years (range: 26-86), and 68 (58%) were female. There were 99 (85%) patients with stage I disease, and 18 (15%) with stage II. Grade was 1 or 2 in 86% of patients. Mean maximum tumour diameter was 3.33cm (range: 0.5-8cm). Of 110 patients with FLIPI scores available, 100 patients had a low FLIPI score (91%), 9 (8%) had an intermediate score, 1 (1%) patient had a high score. Patients were staged with cross-sectional imaging, including a PET scan in 73 (63%) of cases, and bone marrow assessment was completed in 105 (90%) of patients. The most commonly mutated gene in the cohort was CREBBP (n=61; 52.1%), followed by KMT2D (n=45; 38.5%), TNFRSF14 (n=40; 34.2%), STAT6 (n=25; 21.4%), and BCL2 (n=20; 17.1%). BCL2 mutations were more common in patients with stage II (n=8; 44%) compared to stage I disease (n=12; 12%) (p-value=0.003; after FDR adjustment, p-value=0.056). The median number of mutated genes per patient was 4 (range: 0-12, mean 4.0). The median follow-up of living patients was 5.65 years (range: 0.63-18.1 years) and there were 37 progression events in our cohort. CREBBP mutations were associated with shorter TTP (log-rank p-value 0.027), with 5-year TTP estimates of 73.3% vs. 86.0% (Figure 1A). CREBBP mutations were not significantly associated with age, stage, tumor bulk or PET staging. Using Cox univariable analysis for TTP, the hazard ratio (HR) for CREBBP mutations was 2.13 (95% confidence interval (CI) 1.07-4.25; p-value=0.031) and in multivariable analysis adjusting for age and sex the HR was 2.05 (95%CI 1.03-4.10; p-value= 0.041). However, statistical significance was not met after adjusting for the false discovery rate (FDR; p-value 0.621). CREBBP mutations were not significantly associated with OS (log-rank p-value=0.76) (Figure 1B), nor transformation (log-rank p-value=0.9), but the numbers of survival (n=14) and transformation events (n=9) were small. No other genes from the panel were associated with patients' outcomes. Conclusions: In conclusion, we found an association between CREBBP mutations and shorter time to progression in limited-stage FL treated with RT. To our knowledge, this represents a novel genetic prognostic finding in limited-stage FL. Further studies with larger sample sizes are required to confirm the association. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prognostic Factors Other Than Age Drive the Risk of Disease Progression in Adults with Burkitt Lymphoma Treated with DA-EPOCH-R

Prognostic Factors Other Than Age Drive the Risk of Disease Progression in Adults with Burkitt Lymphoma Treated with DA-EPOCH-R

Outcome of primary mediastinal large B-cell lymphoma using R-CHOP: impact of a PET-adapted approach

AbstractCure rates for primary mediastinal large B-cell lymphoma (PMBCL) have improved with the integration of rituximab. However, the type of primary therapy and role of radiotherapy (RT) remains ill-defined. Herein, we evaluated the outcome of PMBCL primarily treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and the impact of an end-of-treatment (EOT) 18F-fluorodeoxyglucose positron emission tomography (PET) scan to guide consolidative RT. Patients ≥18 years of age with PMBCL treated with curative intent rituximab-chemotherapy were identified. Prior to 2005, patients were recommended to receive R-CHOP + RT (RT era). Beginning in 2005, EOT PET was used to guide RT and only those with a PET-positive scan received RT (PET era). In total, 159 patients were identified, 94% were treated with R-CHOP and 44% received RT (78% in RT era, 28% in PET era). The 5-year time to progression (TTP) and overall survival (OS) for the entire cohort were 80% and 89%, respectively, similar across treatment eras. Overall, 10% had refractory disease. In total, 113 patients had an EOT PET scan: 63% negative and 37% positive with a 5-year TTP of 90% vs 71% and 5-year OS of 97% vs 88%, respectively. For those with Deauville (D)-scored PET scans (n = 103), the 5-year TTP for PET-negative cases by Deauville criteria (D1-D3, DX) was 91%, with inferior outcomes for D5 vs D4 (5-year TTP 33% vs 87%, P = .0002). Outcomes for PMBCL treated with RCHOP are favorable and use of a PET-adapted approach reduces RT in the majority of patients. A small proportion have refractory disease and may benefit from an alternate treatment.

Novel methylation gene panel in adjacent normal tissues predicts poor prognosis of colorectal cancer in Taiwan.

BACKGROUNDIt is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis. Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer (CRC).AIMTo estimate whether a methylation gene panel in different clinical stages can reflect a different prognosis.METHODSWe enrolled 120 CRC patients from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select six genes involved in carcinogenesis pathways. Patients were divided into two groups based on the methylation status of the six evaluated genes, namely, the < 3 aberrancy group and ≥ 3 aberrancy group. Various tumor stages were divided into two subgroups (local and advanced stages) on the basis of the pathological type of the following tissues: Tumor and adjacent normal tissues (matched normal). We assessed DNA methylation in tumors and adjacent normal tissues from CRC patients and analyzed the association between DNA methylation with different cancer stages and the prognostic outcome including time to progression (TTP) and overall survival.RESULTSWe observed a significantly increasing trend of hazard ratio as the number of hypermethylated genes increased both in normal tissue and tumor tissue. The 5-year TTP survival curves showed a significant difference between the ≥ 3 aberrancy group and the < 3 aberrancy group. Compared with the < 3 aberrancy group, a significantly shorter TTP was observed in the ≥ 3 aberrancy group. We further analyzed the interaction between CRC prognosis and different cancer stages (local and advanced) according to the methylation status of the selected genes in both types of tissues. There was a significantly shorter 5-year TTP for tumors at advanced stages with the promoter methylation status of selected genes than for those with local stages. We found an interaction between cancer stages and the promoter methylation status of selected genes in both types of tissues.CONCLUSIONOur data provide a significant association between the methylation markers in normal tissues with advanced stage and prognosis of CRC. We recommend using these novel markers to assist in clinical decision-making.

Predictive Model of Progression in Early Stage Non Small Cell Lung Cancer Treated with Stereotactic Ablative Radiation Therapy

There is an emerging interest for combining stereotactic ablative radiotherapy (SABR) with immunotherapy in the management of early stage non small cell lung cancer (ES-NSCLC). To help best select which patients may benefit from immunotherapy in future trials, we aimed to determine the predictive factors of progression free survival (PFS) and time to progression (TTP) in a large cohort of ES-NSCLC patients treated with SABR. A retrospective analysis of patients with stage I–II NSCLC treated with SABR from 2004 to 2015 was conducted. SABR doses of 34-70 Gy in 1-10 fractions were delivered. Cox proportional hazard ratio models were used for analysis of potential predictive variables. The following variables were included in the model: patient age, gender, ECOG performance status, Charlson co-morbidity index, pre-treatment pulmonary function tests (percent forced expiratory volume in 1 second [%FEV1]) and percent diffusing lung capacity for carbon monoxide [%DLCO]), tumor stage, size, histology, location and maximum standardized uptake value (SUVmax) on FDG/PET. Variables with significant association with PFS and TTP in univariate analysis were used for subsequent recursive partitioning analysis (RPA) to identify appropriate cut-off points. A total of 912 patients with a median age of 72 years (range, 46-91) were included. Median follow-up was 59.3 months. Local recurrence, regional recurrence, distant metastasis and second primary lung cancer developed in 10.0%, 11.5%, 20.1% and 7.5% of patients, at a median time to recurrence of 14.9 months (range, 1.5–91.9), 10.5 months (range 1.4–70.7), 11.6 months (range, 0.2–91.9 months) and 23.6 months (range, 1.2–122.4), respectively. Actuarial 3- and 5-year PFS were 52.7% and 39.1%, and 3- and 5-year TTP were 72.2% and 66.7%, respectively. On univariate analysis, age (p=0.0009), ECOG (p<0.0001), Charlson score (p=0.0001), %DLCO (p<0.0001), %FEV1 (p=0.007), non-adenocarcinoma histology (p<0.0001), tumor size (p=0.01) and tumor SUVmax (p=0.0002) were associated with PFS, while %DLCO (p=0.002), tumor size (p=0.002) and tumor SUVmax (p=0.01) were associated with TTP. RPA identified age ≥ 78 years, Charlson score ≥ 5, %DLCO < 71%, %FEV1 < 65%, tumor size ≥ 3 cm and SUVmax ≥ 12 as significant cut-offs for adverse PFS outcome. RPA identified %DLCO < 71%, tumor size ≥ 3 cm and SUVmax ≥ 12 as significant cut-offs for adverse TTP. On multivariate analysis, age (p=0.05), Charlson score (p=0.03), %DLCO (p=0.00001), non-adenocarcinoma histology (p=0.02), and tumor size (p=0.002) remained predictive of PFS. Correlations with biological markers are currently on-going. Age ≥ 78 years, Charlson score≥ 5, %DLCO < 71%, tumor size ≥ 3 cm and non-adenocarcinoma histology were found to be independent predictors of PFS. Patients with %DLCO < 71%, tumor size ≥ 3 cm and SUVmax ≥ 12 had adverse TTP outcomes, suggesting that they may benefit from treatment intensification. A predictive model is being develop and will be presented.

Outcome of primary cutaneous anaplastic large cell lymphoma: a 20-year British Columbia Cancer Agency experience.

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare CD30+ lymphoproliferative disorder with excellent outcomes reported despite frequent cutaneous relapses. Limited information exists on the development of systemic lymphoma. The British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database was searched to identify all adults diagnosed with PCALCL from 1993 to 2013. From 2005, the BCCA endorsed radiotherapy (RT) alone for limited stage with data failing to support chemotherapy. Forty-seven patients were identified with a male predominance (n=31, 66%), median age of 64years and predominantly limited stage (n=40, 85%). Median follow-up was 8·4years. The 5-year time to progression (TTP) was 58% (64% limited versus 29% advanced stage). The 5-year disease-specific survival (DSS) and overall survival was 86% and 75%, respectively. In an as-treated analysis, the 5-year DSS for limited stage patients was similar comparing RT to combined modality treatment or chemotherapy alone but the 5-year TTP favoured RT (82% vs. 33%, P=0·004). The 5-year cumulative risk of developing systemic lymphoma was 14%. Our results confirm the favourable prognosis of PCALCL despite a high relapse rate. Limited stage patients treated with RT alone have excellent outcomes. There is a small risk of systemic lymphoma in PCALCL.

Primary Breast Diffuse Large B Cell Lymphoma: A Distinct Clinical Entity

AbstractAbstract 1618 Introduction:Primary breast lymphoma is a rare type of non-Hodgkin lymphoma (NHL), representing about 1% of breast tumors and 2% of extranodal NHL. Diffuse large B-cell lymphoma (DLBCL) is the most common primary subtype presenting in the breast. Due to the low incidence of primary breast DLBCL, outcome data is limited. The aim of this study was to retrospectively assess the natural history of primary breast DLBCL in the pre and post rituximab eras, with specific emphasis on the incidence of local, systemic and central nervous system (CNS) relapses. Methods:Data was retrospectively collected on patients with primary breast DLBCL from seven USA academic medical centers. Institutional review board approval was obtained at each participating site. Patients were identified through institutional databases and tumor registries at each site. Charts were reviewed to obtain demographic and clinical variables including treatment history and dates of relapse and death when applicable. Only patients with stage I/II disease (involvement of breast and localized lymph nodes) were included. All histologies apart from primary DLBCL were excluded. Overall survival (OS) was calculated from the diagnosis date to the date of death or last follow-up. Time to Progression (TTP) was calculated from diagnosis data until the date of pathological evidence of recurrence or death. Data were summarized using descriptive statistics, and survival was analyzed using the Kaplan-Meier method. Results:Between 1984 and 2012, 75 patients were identified who met the eligibility criteria. The median age was 62 years (range 17–87); 81% presented with a palpable mass; 12% had their disease detected incidentally by mammography; 4% presented with B-symptoms; 59% had right breast involvement; 67% had stage I and 33% had stage II disease. The stage-adjusted international prognostic index (IPI) score was 0 in 28% of patients, 1 in 41%, 2, in 25%, 3 in 4% and 4 in 1%. 91% of patients were treated with chemotherapy; 31% of these were treated in the pre-rituximab era and 69% received rituximab. Radiation therapy (RT) was utilized in 68% of patients and was the only treatment modality in 8% of those receiving RT. 8% of patients received CNS prophylaxis with intrathecal chemotherapy. After a median follow-up of 4.5 years (range 0.6 – 20.6 years), the Kaplan-Meier estimated median TTP was 10.4 years (95% CI 6.2 – 14.6 years) and the median OS was 14.6 years (95% CI 6.5 – 22.6 years). The 5-year TTP and 5-year OS were 65% (95% CI 53–77%) and 75% (95% CI 64–86%) respectively. Among the patients who relapsed, 67% occurred within the first 2 years. A total of 7 relapses in the breast were observed, none in patients treated with combination of chemotherapy and RT. In univariate analysis, rituximab exposure was not associated with any difference in TTP or OS. The stage-adjusted IPI was associated with OS; the 5-year OS was 88% (95% CI 79–98%) in patients with a score of 0–1 versus 48% (95% CI 25–71%) in those with a score of 2–4 (log rank p < 0.001). The very limited-disease group with a stage-adjusted IPI of 0 had a 5-year OS of 94% (95% CI 83–100%) compared to all others who had a 5-year OS of 67% (95% CI 52–81%; log rank p = 0.001). There was no difference in TTP and OS in patients with solitary versus multiple breast masses or between patients with tumors less than versus more than 7cm. Patients receiving RT in addition to chemotherapy had a longer TTP than those who did not (log rank p = 0.03), but RT was not associated with an improved OS. Patients who relapsed and underwent stem cell transplant (SCT) had similar OS to those who never relapsed. Ten patients (13%) had CNS relapse (3 with leptomeningeal disease, 5 with brain parenchymal disease and 2 with both). All CNS relapses occurred within the first 2.8 years from the time of diagnosis. There was no difference in the rate of CNS relapse in the patients who received IT prophylaxis versus those who did not. Conclusions:In this multicenter study, the largest published to date, primary breast DLBCL appears to have a worse prognosis than early-stage DLBCL in nodal or other extranodal sites. RT was associated with improved TTP. Patients who relapsed were successfully salvaged with SCT, and had similar survival times to those who never relapsed. A high CNS relapse rate (∼1 in 8 patients, including parenchymal disease in 70%) was observed. The small numbers preclude definitive conclusions on the value of intrathecal prophylaxis or the utility of rituximab. Disclosures:No relevant conflicts of interest to declare.

Waldeyer’s ring marginal zone B cell lymphoma: are the clinical and prognostic features nodal or extranodal? A study by the Consortium for Improving Survival of Lymphoma (CISL)

There has been controversy surrounding Waldeyer's ring (WR), especially focused on the question of whether it should be regarded as a nodal or an extranodal site. We conducted retrospective analyses of marginal zone B cell lymphomas involving WR (WR-MZLs) to observe their clinical features and prognosis, with specific regard to the nodal-or-extranodal question. A total of 52 patients with histological diagnosis of WR-MZL were retrospectively analyzed. The most common involvement site was the tonsil (40.4 %). Ann Arbor stage III/VI disease was present in 48.1 % (25 of 52). The response rate of the 27 stage I/II patients was 88.9 %, with 21 complete remissions and three partial remissions. The median time to progression (TTP) was 3.7 years (95 % CI 2.5-4.9 years). The estimated 5-year TTP and overall survival rates were 39.4 and 90.5 %, respectively. In a comparison with the historical data regarding extra-WR MALT lymphoma and nodal MZL (N-MZL), MALT lymphoma showed better TTP results than did WR-MZL and N-MZL (P < 0.001).

Prognostic Value of 18F-FDG Positron Emission Tomography Used for Assessment of the First Line Therapy in 410 Diffuse Large B-Cell Lymphoma Patients: A Daily Practice Evaluation Before and After the Prescription of This Metabolic Imaging Technique,

Abstract 3686 Background:18F-FDG Positron Emission Tomography (PET) had improved initial staging and response assessment after first line therapy of Diffuse Large B-cell Lymphoma (DLBCL). While the prognostic role of PET after induction therapy (interim PET) remains controversial, the outcome of patients with positive PET at the end of initial treatment is clearly worse as compared with negative ones. In clinical practice, many PET are performed before, during and after first line therapy for patients with DLBCL. A hypothetical effect of therapeutic decisions, guided by PET results, on DLBCL patients' outcome remained questionable. We evaluated our daily practice about PET prescription during first line therapy to explore how a complete PET could influence the DLBCL prognosis.Patients and Methods: From 1996 to 2008, 410 patients with DLBCL received first-line therapy in our institution. No selection was made on initial therapeutic intent (curative/palliative), medical history, patient's age or initial type of chemotherapy (CT) to be in accordance with daily practice setting. Study population was described and Overall Survival (OS) and Time To Progression (TTP) analysis was performed using the Kaplan Meier method. OS and TTP were compared between patients with or without PET, using the Log-Rank test. We first focused on interim PET considering patients who performed at least 3 months of the induction therapy (n=380). PET at the end of treatment were studied on patients who achieved a major part of their consolidation treatment (at least 6 months, n=354). As it was a practical study, the PET interpretation methods were not taken into account. Results:Median age at diagnosis was 65 years (range: 19–97). Most patients received CHOP-like CT (53%) or high-dose CHOP CT (31%). Rituximab was associated to CT for 269 patients (66%). PET was performed at initial staging, after induction therapy and at the end of initial treatment respectively on 77, 72 and 94 patients. We first observed that patients who had a pre-treatment PET presented a significantly higher rate of III-IV Ann Arbor stage than patients evaluated by conventional methods (71% vs. 57%, p =.021). Patients who had an interim PET were younger (median age: 55 vs. 67 years, p <.001), presented a higher age-adjusted IPI score (2–3, 66% vs. 47%, p =.004) and were more frequently treated by rituximab (96% vs. 61%, p <.001) than patients who did not have a PET, that is in accordance with the date of approval of rituximab for DLBCL in 2002. The same observation was done for patients who had a PET at the end of the treatment. No difference in TTP was observed between patients who had an interim PET and patients evaluated by conventional methods (p =.543), with 5-year TTP rates of 65.6% (CI95% [51.0–76.8]) and 70.3% (CI95% [64.5–75.3]) respectively. Similarly, no difference in OS was observed between these groups. Neither OS nor TTP were found to be statistically different between patients evaluated at the end of treatment with a 5-year TTP rates of 72.4% (CI95% [61.5–80.7]) for patients who performed a TEP at the end of the treatment and 73.8% (CI95% [67.6–78.9]) (p =.653) for the others. Preliminary results showed a worse prognosis for patients who had a positive PET at completion of first line therapy with a 5-year OS rate of 50.0% (CI95% [22.9–72.2]) compared with 84.4% (CI95% [70.4–92.1]) for patients with negative PET (p =. 001). However, no observe a prognostic value of positivity of interim PET performed at mid-treatment was observed. Conclusions:Results of this retrospective clinical practice study are consistent with the usefulness of PET for initial staging of DLBCL patients and a poor prognosis of positive PET at the end of first line therapy. Using PET for evaluation of treatment response after induction therapy or after treatment completion was not found to be significantly associated with patient's prognosis. Modification of therapeutic decision based on PET results need to be more accurately explored with a prospective clinical trial. Disclosures:No relevant conflicts of interest to declare.

R-CHOP with Etoposide Substituted for Doxorubicin (R-CEOP): Excellent Outcome in Diffuse Large B Cell Lymphoma for Patients with a Contraindication to Anthracyclines.

Abstract 408 Introduction:R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) is the current standard of care for the treatment of diffuse large B cell lymphoma (DLBCL). Doxorubicin has an integral role but is associated with significant toxicity. The omission of doxorubicin in patients who are frail, have poor baseline cardiac function or who have previously received anthracycline therapy may compromise outcome. However, the recent introduction of rituximab may allow for improved outcomes without the use of doxorubicin. We assessed the efficacy of substituting etoposide for doxorubicin for patients with a contraindication to anthracyclines. Patients and Methods:Treatment guidelines in British Columbia (BC) recommend the substitution of etoposide for doxorubicin in standard dose R-CHOP for patients with DLBCL who have a contraindication to anthracyclines (R-CEOP). Etoposide is administered at a dose of 50 mg/m2 IV on day 1 and 100 mg/m2 PO on days 2 and 3 of each cycle. Patients with limited stage disease receive 3-4 cycles of chemotherapy with or without radiation therapy; patients with advanced stage disease receive 6 cycles of chemotherapy. We performed a retrospective population-based analysis using the BC Cancer Agency Lymphoid Cancer and pharmacy databases and included all patients with newly diagnosed DLBCL who were treated with curative intent with R-CEOP from December 2000 to March 2009. Patients who began treatment with R-CHOP but then switched to R-CEOP (due to intolerance or because a maximum threshold of anthracycline dosing was reached) were also included in the analysis if R-CEOP was administered for more than 50% of cycles delivered. Outcome of this population was compared with a 2:1 control group treated with R-CHOP in the same time period and matched for age, clinical stage and International Prognostic Index (IPI). End points were time to progression (TTP) and overall survival (OS). Results:We identified 81 patients treated with R-CEOP who met the stated inclusion criteria. Clinical characteristics were as follows: median age 73 y (range 34-93), 55 (68%) male, 15 (18%) limited stage and 66 (82%) advanced stage. Adverse prognostic factors according to the IPI were as follows: 85% age > 60 y, 58% stage III/IV, 31% PS > 1, 43% elevated LDH, and 12% > 1 extranodal site. IPI score: 19 (23%) low risk, 33 (41%) low-intermediate, 18 (22%) high-intermediate, and 11 (14%) high risk. Reasons for etoposide substitution were: 71 (88%) cardiac contraindication, 7 (9%) prior exposure to anthracyclines and 3 (4%) other co-morbidities. 72 (89%) patients received rituximab as part of the treatment, 25 (31%) received partial treatment with R-CHOP and then switched to R-CEOP and 56 (69%) received no anthracycline therapy. The control group included 162 randomly chosen patients matched for age, stage and IPI score and treated with R-CHOP. At a median follow-up of 28 months (range 3-86), 33/81 (41%) R-CEOP patients had died (23 with lymphoma, 3 treatment toxicity, 7 unrelated causes). The 5-year TTP was similar for patients treated with R-CEOP compared to patients in the R-CHOP control group, 57% versus 62%, respectively (p=0.21). (Fig. 1) The 5-y OS was lower for patients receiving R-CEOP compared with the R-CHOP control group (49% versus 64%, p=0.02), reflecting the underlying co-morbidities and frailty of this population. Interestingly, the 5-y TTP and 5-y OS rates were similar for patients in the R-CEOP cohort who had received partial treatment with an anthracycline and those who had received no anthracycline treatment (p=0.49 and p=0.77, respectively). [Display omitted] Conclusions:A significant proportion of patients with DLBCL who are unable to receive anthracycline-based therapy can be cured with the etoposide-substituted regimen R-CEOP. R-CEOP is well tolerated even by patients with numerous co-morbidities. Moreover, the outcome of these patients does not appear to be significantly different compared to a similar population treated with standard R-CHOP. Disclosures:No relevant conflicts of interest to declare.

High-dose chemotherapy as a consolidation approach in advanced ovarian cancer: long-term results

The aim of this study was to assess the long-term impact of high-dose chemotherapy (HDC) as consolidation in a large series (n = 55) of advanced chemosensitive ovarian cancer patients who were optimally cytoreduced at time of first surgery or at interval debulking surgery (IDS). HDC consisted of carboplatin (600 mg/m(2) days 1 and 2), etoposide (450 mg/m(2) days 1 and 2) and melphalan (50 mg/m(2), days 3 and 4). The primary endpoint of the study was the assessment of time to progression (TTP) and overall survival (OS). In September 2000 the overall population had a median follow-up of 55 months (range 17--137) and a TTP of 35 months with a 5-year TTP rate of 35% (CI 95%: 21--49) whereas OS averaged 75 months with a 5-year OS of 59% (CI 95%: 45--73). In patients achieving optimal primary cytoreduction the median TTP was 44 months with a 5-year rate of 43% (CI 95%: 26--60). In the same series the 5-year OS rate was 62% (CI 95%: 45--79) (median OS = 75 months). In patients who were optimally cytoreduced at the time of IDS the median TTP was 25 months and the 5-year TTP rate was 22% (CI 95%: 3--41) and median OS was 46 months with a 5-year OS rate of 50% (CI 95%: 27--73). HDC with hematopoietic support could represent an effective approach for the treatment of advanced optimally cytoreduced ovarian cancer patients with chemosensitive disease. Patients who underwent IDS because of unresectable tumors at the time of first surgery had the greater survival benefit from HDC.