scholarly journals Treatment of Ewingʼs sarcoma in children and adolescents: new vision

2021 ◽  
Vol 8 (3) ◽  
pp. 30-42
Author(s):  
O. M. Romantsova ◽  
D. V. Nisichenko ◽  
D. B. Khestanov ◽  
V. V. Khairullova ◽  
A. Z. Dzampaev ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Ewing Sarcoma ◽  
Response Rate ◽  
Disease Recurrence ◽  
Local Relapse ◽  
Primary Treatment ◽  
Study Group ◽  
Time To Progression ◽  
First Relapse

Introduction. Over the past decades, a significantly greater understanding of the morphology and molecular biological characteristics of tumors of the Ewing sarcoma family (ESFT) has been achieved. More than 70 % of relapses occur within 2 years from the date of diagnosis. In about 2/3 of cases, relapse occurs in distant places; this type of relapse is especially common in patients who initially have metastases. On the contrary, isolated local metastasis most often (in 1/5 of cases) occurs in patients with a localized form of the disease. In half of the patients, a relapse of the disease was detected during a routine examination, was asymptomatic and was a chance find.Purpose of the study – to evaluate the effectiveness of anti-relapse treatment in patients with ESFT, to develop an algorithm for a personalized approach, to improve the results of overall and relapse-free survival in children and adolescents with ESFT.Materials and methods. Our study included patients with a confirmed diagnosis of Ewing sarcoma (ES), who received treatment from 2008 to 2019. The analysis of follow-up data was closed on 19.02.2021. The study included 274 patients aged 6 months to 18 years, the average age was 11.6 years. Up to 1 year in our study there were 2 children. Twelve (4.3 %) patients went out of follow-up within 2 to 9 months from the start of treatment; we did not include them in the subsequent analysis. Analyzed were 262 patients with ES who received treatment according to the protocols at the Research Institute of Pediatric Oncology and Hematology of the N.N. Blokhin National Medical Research Center of Oncology. A relapse of the disease was revealed in 48 (18.3 %) children out of 262 – the study group; 58 (22.1 %) patients showed disease progression during treatment. In 70.8 % (34/48) patients had an isolated relapse, in 14 (29.2 %) cases – a combined one. The defeat of only the lung tissue with a relapse of the disease occurred in 19/48 (39.6 %) cases, local relapse without metastasis – 7/48 (14.5 %) cases. In general metastatic lung disease occurred in 66.6 % of cases. The defeat of the brain and lymph nodes occurred in 4 %. Most of the patients were in the group from 11 to 17 years, inclusive – 38/48 patients, which amounted to 79 %. All 48 patients from the study group received anti-relapse therapy depending on the duration of the disease relapse. For late relapses the primary treatment regimen was used: alternating courses of chemotherapy with vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide. In early relapses two regimens were most used: vincristine/topotecan/cyclophosphamide and vincristine/irinotecan/temozolomide (VIT). The positive response rate with the antirelapse VIT regimen was 60 %, and the time to progression was 7.6 months. With the topotecan regimen the response rate was 45 % and the time to progression – 7 months.Results. The overall survival (OS) rate of patients when a relapse was detected was significantly (p £ 0.05) higher when compared with the group of patients who had progression of the disease, which is associated with the effect of anti-relapse chemotherapy. When analyzing OS of patients with ES it should be noted that the 5-year survival rate of all patients (n = 262) was 66.3 ± 3.3 %, compared with the group of patients with confirmed relapse (n = 48) – 53 ± 8.1 %. The median in the group of patients with relapse was 39.3 months. The follow-up time in the group with recurrent ES disease averaged 52.2 ± 32.3 months (from 12.6 to 142 months). OS of patients was analyzed depending on the interval of disease recurrence. The Interval No. 1 was from the beginning of the main treatment to the first relapse, with a median of 37.2 months. Interval No. 2 – from the date of the first relapse to the date of the second relapse with a follow-up time of 58.8 ± 29.1 months (from 28.6 to 108 months), the median was not reached. The second relapse occurred significantly less frequently than the first relapse (p = 0.000001).Conclusion. The outcome for patients with recurrent ES remains poor, and a standard approach to their treatment has not yet been established. Standard first and second lines chemotherapy can be effective in most patients in terms of reducing symptoms and increasing the time to further progression, but complete remission remains hard to reach. Further multidisciplinary study of prognostic factors, effects of various treatment regimens and protocols, study of the inclusion of targeted drugs in the therapy program is required.

Treatment and outcome of intracranial ependymoma after first relapse in AIEOP 2 nd protocol

2021 ◽  
Author(s):  
Maura Massimino ◽  
Francesco Barretta ◽  
Piergiorgio Modena ◽  
Pascal Johann ◽  
Paolo Ferroli ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Local Relapse ◽  
Salvage Treatment ◽  
Dose Fractionation ◽  
Molecular Subgroup ◽  
Intracranial Ependymoma ◽  
First Relapse ◽  
Multivariable Analyses ◽  
The Impact

Abstract Background More than 40% of patients with intracranial ependymoma need a salvage treatment within 5 years after diagnosis, and no standard treatment is available as yet. We report the outcome after first relapse of 64 patients treated within the 2 nd AIEOP protocol. Methods We considered relapse sites and treatments ,i.e. various combinations of complete/incomplete surgery, if followed by standard or hypo-fractionated radiation(RT) ± chemotherapy(CT). Molecular analyses were available for 38/64 samples obtained at first diagnosis. Of the 64 cases, 55 were suitable for subsequent analyses. Results The median follow-up was 147 months after diagnosis, 84 after first relapse, 5-year EFS/OS were 26.2%/30.8% (median EFS/OS 13/32 months) after relapse. For patients with a local relapse(LR), the 5-year cumulative incidence of second LRs was 51.6%, with a 5-year event-specific probability of being LR-free of 40.0%. Tumor site/grade, need for shunting, age above/below 3 years, molecular subgroup at diagnosis, had no influence on outcomes. Due to variation in the RT dose/fractionation used and the subgroup sizes it was not possible to assess the impact of the different RT modalities. Multivariable analyses identified completion of surgery, absence of symptoms at relapse, and female sex as prognostically favorable. Tumors with a 1q gain carried a higher cumulative incidence of dissemination after first relapse. Conclusions Survival after recurrence was significantly influenced by symptoms and completeness of surgery. Only a homogeneous protocol with well posed, randomized questions could clarify the numerous issues, orient salvage treatment and ameliorate prognosis for this group of patients.

Follow-Up Results of a Prospective, Multicenter, Open-Label Study of Oral Fludarabine Phosphate in Patients with Previously Untreated B-CLL.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2128-2128
Author(s):  
Jean-Francois Rossi ◽  
A. Van Hoof ◽  
K. De Boeck ◽  
S. A. Johnson ◽  
D. Bron ◽  
...  
Keyword(s):  
Disease Progression ◽  
Median Time ◽  
Response Rate ◽  
Time To Progression ◽  
Open Label ◽  
Overall Response ◽  
Fludarabine Phosphate ◽  
Duration Of Response ◽  
Grade 3

Abstract The IV formulation of fludarabine phosphate is an effective treatment in patients with B-cell chronic lymphocytic leukemia (B-CLL), yielding overall response rates of 60% to 80%. An oral formulation of fludarabine phosphate has been developed. In a previously published multicenter, open-label, phase II clinical trial, 81 previously untreated B-CLL patients received 10-mg tablets of fludarabine phosphate (Fludara® oral) 40 mg/m2/day for 5 days, repeated every 4 weeks. The primary endpoint of the trial was response rate, and secondary endpoints included safety and quality of life assessments. Of 81 patients (mean age, 61.2 years; range, 30–75 years) with previously untreated B-CLL, 81.5% were classified as Binet stage B or C. The overall response rate (complete response [CR] + partial response [PR]) using National Cancer Institute (NCI) criteria was 80.2% (12.3% CR and 67.9% PR) and the median time to progression was 841 days (range, 28–1,146 days) (Rossi JF, et al. J Clin Oncol2004;22:1260–1267). The most frequently reported grade 3/4 adverse event was myelosuppression: WHO grade 3/4 hematologic toxicities included granulocytopenia (32.1%), anemia (9.9%), and thrombocytopenia (4.9%). This analysis reports on the long-term follow-up of this cohort during the period from November 2001 to November 2004. Of the 74 patients eligible for the survival analysis, 61 were also assessed for duration of response using NCI criteria: 9 CR (14.8%) and 52 PR (82.2%). During the 3-year follow-up period, 22 (29.7%) patients did not progress. For those who progressed, median time to progression was 29.7 months, and median duration of response was 22.9 months. In 41 (80.4%) of these patients, an increase in circulating lymphocytes was reported as evidence of disease progression. In 23 patients (45.1%), an increase in the sum of the products of at least 2 lymph nodes and/or appearance of new palpable nodes was reported as evidence of disease progression. During the indicated follow-up period, 37 patients (50%) received subsequent treatment. Twelve patients (16.2%) died during the follow-up period: 7 patients (58.3%) due to disease progression, 3 patients (25.0%) due to adverse events, and 2 patients (16.7%) due to other causes. Results from this study suggest that oral fludarabine phosphate is clinically effective and well tolerated by patients with previously untreated B-CLL. Moreover, these data demonstrate that oral fludarabine phosphate achieves response rates and duration of response comparable to those achieved with first-line fludarabine phosphate IV therapy.

The Role of Serum Immunoglobulin Free Light Chain In Response and Progression In Waldenstrom Macroglobulinemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3095-3095
Author(s):  
Xavier Leleu ◽  
Wanling Xie ◽  
Meghan Rourke ◽  
Ranjit Banwait ◽  
Renee Leduc ◽  
...  
Keyword(s):  
Median Time ◽  
Research Funding ◽  
Response Rate ◽  
Early Response ◽  
Response To Therapy ◽  
Time To Progression ◽  
Therapy Initiation ◽  
M Spike

Abstract Abstract 3095 Introduction: Waldenstrom macroglobulinemia (WM) is a low grade B cell lymphoma characterized by the secretion of IgM protein in the serum. The IgM level lacks sensitivity due to its prolonged half-life. The serum free light chain (sFLC) assay has shown significant clinical application in plasma cell dyscrasias, specifically in multiple myeloma, and is used to monitor response to therapy. In this study, we sought to examine the role of sFLC in the response and progression of patients with WM. Methods: This study was performed using serum collected from a homogeneous cohort of patients diagnosed with WM and uniformly treated on a phase 2 trial using the combination of bortezomib with rituximab, previously untreated (N=26) or relapsed and or refractory to prior therapy (N=37). Patients eligible for this analysis must have measurable sFLC levels at baseline. A total of 48 patients were included. FLC response is defined as achievement of normal iFLC value or 50% decrease from baseline in the iFLC level during therapy and follow-up. Concordance between FLC and IgM response rate was evaluated using Kappa statistics. Correlation was evaluated using Spearman correlation coefficient. Time to progression was estimated using Kaplan-Meier methodology. We also did landmark analysis to compare overall response rate and time to progression by FLC or IgM response status at 2 months after therapy initiation; Fisher Exact test or Log-rank test were used. Results: The median iFLC value was 103.50mg/L (range 22.5–3540), the median kappa over lambda ratio was 13.45 (0.01-665), and the median serum IgM value by nephlometry was 3995 mg/dL (537-10,800). Overall, as per M spike response criteria, 29 (60%, 90% CI: 48%, 72%) patients responded, e.g. had partial response or better, and 19 patients failed to obtain response. Using serum IgM protein measurement by nephlometry during therapy and follow up post-therapy, 35 (73%, 90% CI: 60%, 83%) patients responded with a PR or better (>50% decrease), with 3 (6%) having normalization of their serum IgM. In comparison, iFLC response during treatment and follow up occurred in 38 (79%, 90% CI: 67%, 88%): with 2(4%) having normalization of value, 21(44%) having 50% reduction and 15(31%) having both. The time to iFLC response and IgM response among patients who achieved response by both criteria was calculated (N=33). The median time to iFLC response was 2.1 months (range 0.9–28.7months), while the median time to IgM response was 3.0 months (0.9-14.7) (p=0.07). The median time to progression per the protocol was 18.9 months (95% CI:10.5-NR). The Kappa concordance between iFLC 25% increase and M spike progression was 0.63 (95% CI: 0.41–0.84). This showed a better concordance compared to using the iFLC >50% definition (kappa=0.58, 95% CI: 0.35, 0.81), indicating that progression using iFLC>25% would be a better definition for patients with WM. The median time to progression by iFLC>25% increase was 13.7 months (95% CI:10.9-19.4) and the median time to IgM >25% increase was 14.6 months (95% CI: 9.5–19.1), showing a more rapid detection of progression by iFLC compared to M spike and IgM measurements. We next examined whether attaining a response using iFLC can be a predictor of overall response to therapy. Seventeen patients (35%) achieved an iFLC response at 2 months after therapy initiation. Patients with early iFLC response were more likely to have intermediate/high ISS-WM stage, elevated B2M or low Hemoglobin<11.5 gm/dL (p<0.05). Early iFLC response was related to overall IgM response during therapy and follow up (p=0.02). In multivariable models when adjusting for ISS stage, B2M or Hgb, there was no significant association between FLC early response and TTP either by protocol, FLC or IgM criteria. However, there was trend that early response was related to prolonged TTP especially when adjusting for hgb risk factors (HRs ranges from 0.63∼0.80, p>0.3 for various TTP endpoints. Conclusion: iFLC may be a useful marker of tumor measurement that correlates well with IgM and M spike measurements. The time to iFLC response was shorter by 1 month compared to IgM or M spike measurement. The median time to progression by iFLC was shorter by 1 month compared to IgM. There was a trend that early response was related to prolonged TTP when adjusting for other risk factors. Disclosures: Leleu: Celgene: Consultancy, Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Chugai: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; LeoPharma: Consultancy, Honoraria.

Single-agent bortezomib in previously untreated multiple myeloma (MM): Results of a phase II multicenter study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7504-7504 ◽  
Author(s):  
K. Anderson ◽  
P. Richardson ◽  
A. Chanan-Khan ◽  
R. Schlossman ◽  
N. Munshi ◽  
...  
Keyword(s):  
Response Rate ◽  
Axonal Neuropathy ◽  
Single Agent ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Time To Progression ◽  
Large Fiber ◽  
Grade 3 ◽  
Dose Modifications

7504 Background: Bortezomib is effective in relapsed and/or refractory MM. This trial evaluated its efficacy and safety as monotherapy in previously untreated MM. Methods: Pts with untreated, symptomatic MM were eligible, with pts receiving concomitant steroids, platelet count < 30 × 109/L, or grade > 2 peripheral neuropathy [PN] excluded. Endpoints included response rate (RR) [Bladé criteria], time to progression, safety, incidence/severity of PN, and effect of dose modifications on PN. Pts received bortezomib 1.3 mg/m2 (d1, 4, 8, 11 every 21d) for 8 cycles. Comprehensive neurologic evaluation including electrophysiologic testing [NCS] and skin biopsy was performed in a subset of pts (n = 34). Results: Sixty-six pts (47% with stage III MM) were treated and 60 pts are evaluable for response, with an overall RR of 38% (CR 10%, PR 28%). PN was reported in 55% (36/65) pts (23 grade 1, 12 grade 2). One pt with grade 3 PN was discontinued. Other common treatment-associated adverse events reported to date include grade 1–2 fatigue in 21% (6/29), and rash in 17% (5/29) pts. Preliminary analysis shows PN improved or resolved in 75% (6/8 pts, with available follow-up data) with dose reduction. At baseline, small-fiber neuropathy (SFN) was seen in 52% (17/33) and large fiber axonal neuropathy (LFN) occurred in 9% (3/34) pts by NCS. SFN worsened in 41% (7/17) pts with baseline SFN. After completion of treatment, new SFN was seen in 33% (8/24) pts and LFN in 17% (4/24) pts by NCS. Conclusion: Single agent bortezomib is active in newly diagnosed MM pts (CR 10%), has manageable toxicity and offers a steroid-sparing approach. Underlying SFN appears more common in MM than previously appreciated and can also develop during bortezomib therapy, with symptomatic PN improving with dose modification. [Table: see text]

NCCTG phase I/II trial (N9943) of gemcitabine and pemetrexed in patients with biliary tract or gallbladder carcinoma: Phase II results

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4578-4578 ◽  
Author(s):  
R. R. McWilliams ◽  
N. R. Foster ◽  
F. J. Quevedo ◽  
R. F. Marschke ◽  
J. W. Kugler ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Median Overall Survival ◽  
Hepatic Dysfunction ◽  
Response Rate ◽  
Time To Progression ◽  
Medical Problems ◽  
Folate Supplementation ◽  
Stopping Treatment ◽  
Grade 3

4578 Background: Gemcitabine is commonly used in patients with cholangiocarcinoma with a response rate of 20–30% and median overall survival of 6–10 months. Pemetrexed’s mechanism of action and tolerability in patients with hepatic dysfunction makes it a potential agent for cholangiocarcinoma. Methods: Patients with unresectable, previously untreated biliary tract cancers were eligible for participation. Patients received pemetrexed 500 mg/m2 IV over 10 minutes and gemcitabine 800 mg/m2 IV at 10 mg/m2/minute on days 1 and 15 of an every 4 week schedule with vitamin B12 and folate supplementation. The primary end-point is 6-month survival with a planned accrual of 59 patients. Results: 58 eligible patients are included in this analysis. 93% had metastatic disease. Median age was 61 (range: 40 - 81). Median follow-up was 6.5 months (range: 3.3 - 23.2). Median of 3 cycles of treatment was given (range: 1 - 10). Reasons for stopping treatment included disease progression (57%), adverse events (20%), refusal (17%), death on- study (4%), and other medical problems (2%). 6-month survival was 52% (95% CI: 40 - 68%). Median survival was 6.3 months (95% CI: 5.4 - 8.0 months) and median time-to-progression was 3.8 months (2.4 - 5.0). 46 of 58 patients (79%) experienced at least one grade 3+ AE (at least possible attribution), and 26 patients (45%) experienced at least one grade 4 AE (at least possible attribution), most of which were due to grade 4 neutropenia. Conclusions: This study shows similar results to what would be expected with gemcitabine alone. The addition of pemetrexed, as with other agents, has not significantly enhanced the activity of gemcitabine. Supported by NIH Grant CA25224- 18. [Table: see text] No significant financial relationships to disclose.

P3808iBox-CRT: Better response, less complicated, equally fast

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Aguiar Ricardo ◽  
A Nunes-Ferreira ◽  
J Rigueira ◽  
J Agostinho ◽  
R Santos ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Response Rate ◽  
Control Group ◽  
Conduction Delay ◽  
Study Group ◽  
Automatic Assessment ◽  
Systolic Volume ◽  
End Diastolic Volume ◽  
The Mean

Abstract Introduction The optimization of the left ventricle (LV) pacing site guided by the electrical delay increases CRT response rate (RR), however it's necessary to develop technology that allows its universal use. Purpose The aim is automatically, and operator-independent, access the conduction delay between the right ventricular (RV) stimulus and the LV available veins in order to select the LV pacing site. It is further intended to compare the total procedure and radiation times in relation to an historical control group. Methods Prospective, single-center study that included patients undergoing CRT implant according to the current ESC Guidelines. All patients were submitted to a clinical, electrocardiographic and echocardiographic basal evaluation prior to CRT implantation and at 6 months of follow-up. To evaluate conduction delays between the RV lead and the LV available veins (RV-LV delay), an external interface - intelligent Box for CRT (iBox-CRT) was used. Four measurements in at least two different tributary veins were made. The implant of all the LV leads was guided by the longest measured delay. A positive response to CRT was defined as an improvement of >10% in left ventricle ejection fraction (LVEF) or a reduction of end-systolic volume (ESV)>15%. The results were compared to a control group (CG) of pts submitted to CRT implantation in the conventional way. Results 60 patients were included (68.3% males, 38% ischemic, mean age 67.4±10.2 years) and submitted to CRT implant (37 CRT-P; 23 CRT-D). At basal evaluation, LVEF was 28±7%, end-diastolic volume (EDV) was 200±73ml and ESV 145±64ml. CG (n=51) had similar characteristics. The RR was 85.7%, significantly higher compared to the CG (55.9%, p=0.003). The ESV reduced 38.2±3% in responders vs 5.7±2% in non-responders (NR) (p=0,005), EDV reduced 33.3±16% in responders vs 13.6±10% in NR (p=0.002), the mean LVEF improved 11% in responders vs −1% in NR (p=0.02). At follow-up, the mean ESV in the study group (SG) was 89±44 ml vs 132±75ml in the CG (p=0.002) and the EDV 136±51 vs 190±78 (p=0.007). In addition to a much better response rate, the responders in the study group had significantly higher mean LVEF at follow-up (39±11% vs 37±7%, p=0.032). The mean intra-procedure RV-LV delay was 187±34mseg. In the responder group the baseline delay was usually higher (190±35 msec) vs NR group RV-LV delay (165±23 msec; p=NS). Compared with CG, the automatic assessment of RV-LV delay with iBox-CRT did not increase fluoroscopy time (15±16min vs 18±16; p=NS) and shortened procedure time (65±34 vs 108±83min, p<0.005). Conclusions The iBox-CRT use enabled an automatic and operator independent RV-LV delays measurement, in order to implant the LV lead at the most delayed site. This technique translated into a major increase in CTR response rate, not compromising the procedure duration nor increasing the radiation exposure.

Evaluation of routine image follow-up in nonmetastatic colorectal cancer after curative surgical resection.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 524-524
Author(s):  
Lara Azevedo Diniz ◽  
Amanda Karani ◽  
Diogo De Brito Sales ◽  
Larissa Machado ◽  
Milton Jose Barros
Keyword(s):  
Colorectal Cancer ◽  
Disease Recurrence ◽  
Early Recurrence ◽  
Primary Treatment ◽  
Cancer Center ◽  
Published Data ◽  
Ct Image ◽  
Survival Difference ◽  
Pattern Of Recurrence

524 Background: Follow-up surveillance is performed after primary treatment in colorectal cancer (CRC), but it is controversial in the literature the real benefit of an intensive examination in terms of outcomes and resources. Intensive follow-up after surgery for colorectal cancer has been challenged by some new published data (CEA watch trial and FACS trial). These new data suggest that a less intensive follow-up program based on carcinoembryonic antigen (CEA) measurements or CEA-Triggered imaging would be enough to detected most of the recurrences. We believe that there is a high percentage of patients with recurrence disease and normal CEA value, for whom image screening would be necessary to detect early disease recurrence suitable to metastasectomy with curative intention. Methods: This is a retrospective study that included 372 patients from a tertiary cancer center in São-Paulo (Brazil) diagnosed with colorectal adenocarcinoma stages I to III. We observed, after primary treatment, a pattern of recurrence detected either by CT (computed tomography) imaging only or CEA elevation and CT image in combination. Results: Out of the 372 patients analyzed, 110 (29,5%) had recurrent disease with a median follow-up time of 34 months. Of the 110 recurrences detected, 75 (68,18%) were detected by CEA elevation in combination with CT image, 33 (30%) were detected only by CT image and 2 (1,81%) neither by CT nor by CEA alteration. There was no clinic feature that would predict pattern of recurrence when analyzed by qui square test. Metastasectomy rate from this analysis 53,6% and it was similar among both groups. Recurrence rate after metastasectomy was 59,3%. There is a 5-year overall survival difference between patients that underwent or not metastasectomy (79,4% vs. 54%, p 0,01). Conclusions: CEA-based follow-up program and CEA-triggered imaging failed to detect early recurrence in almost 30% of cases. We believe that this number is high enough to allow us to continue to perform image test during CRC follow-up.

Primary Treatment of Waldenstrom's Macroglobulinemia with Dexamethasone, Rituximab and Cyclophosphamide (DRC): Final Analysis of a Phase II Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 438-438 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Evdoxia Hadjiharissi ◽  
Marie-Christine Kyrtsonis ◽  
...  
Keyword(s):  
Median Time ◽  
Progressive Disease ◽  
Alkylating Agents ◽  
Primary Treatment ◽  
Line Treatment ◽  
Second Line ◽  
Time To Progression ◽  
Minor Response ◽  
A Minor

Abstract Abstract 438 Between November 2002 and April 2006, 72 patients with Waldenstrom's Macroglobulinemia (WM) were enrolled in this multicenter trial of primary treatment with DRC which consisted of dexamethasone 20mg IV followed by rituximab 375 mg/m2 IV on day 1 and oral cyclophosphamide 100 mg/m2 bid on days 1 to 5 (total dose 1000 mg/m2). DRC courses were repeated every 21 days for six courses and then patients without progressive disease were observed without treatment. Patient characteristics, toxicity and response data have been reported previously (Dimopoulos et al, J Clin Oncol 2007;25:3344): 83% of patients achieved a response including 7% complete, 67% partial and 9% minor responses. In June 2012 we updated this study (minimum follow-up >6 years) in order to assess time to progression, time to next treatment, type and response of second-line treatment, overall survival (OS) and cause-specific survival (CSS) in which deaths unrelated to WM or complications of treatment were censored. Second line treatment was administered to patients who experienced progressive disease and also met criteria for treatment requirement based on consensus recommendations (Kyle et al, Sem Oncol 2003;30:116). The median time to progression was 35 months (95% Confidence Interval: 22–48 months) and the median time to next treatment requirement was 51 months. Among several factors who were analyzed for their possible correlation with shorter time to progression, only lymphadenopathy was significant (p=0.028). Among 40 patients who received second line treatment, 28 patients were retreated with either rituximab alone (n=7) with DRC (n=11) or with rituximab combined with other agents (n=10) and 23 patients (82%) achieved a minor response or better. The remaining 12 patients were treated with alkylating agents (n=5), with nucleoside analogues (n=4) with bortezomib (n=2) or with high dose therapy (n=1) and 8 patients achieved a minor response or better. So far 35 (49%) patients have died including 15 patients from unrelated causes (4 lung cancer, 1 bladder cancer, 1 melanoma, 1 gastric cancer, 1 pancreatic cancer, 4 complicated of heart diseases, 2 stroke and 1 pancreatitis). One patient, who received further therapy with fludarabine, developed myelodysplastic syndrome and 2 patients developed diffuse large-B cell lymphoma (one after DRC and one after multiple treatments which included alkylating agents and fludarabine). The probability for 5-year OS and CSS is 62% and 78%, respectively while median OS and CSS is 95 and 104 months respectively (figure). Post progression survival was 82 months and median survival after second line therapy was 82 months. The International Prognostic Staging System (IPSS) is predictive for OS. The probability for 5-year OS is 100%, 67% and 48% for patients with low-, intermediate- and high- risk WM (p=0.005). We conclude that this long-term follow-up analysis of the original phase II study showed that the DRC regimen is associated with a significant median time to progression of about 3 years and that most patients who develop disease progression respond again to rituximab-based regimens. So far, this regimen has not been associated with development of secondary myelodysplasia. The DRC regimen represents an active and safe treatment choice for patient with symptomatic WM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cutaneous Ewing Sarcoma and Ewing Sarcoma of the Bone: Distinct Diseases

2018 ◽  
Vol 11 (3) ◽  
pp. 729-734 ◽  
Author(s):  
Montreh Tavakkoli ◽  
Lisa Mueller
Keyword(s):  
Adjuvant Chemotherapy ◽  
Soft Tissue ◽  
Skin Lesion ◽  
Children And Adolescents ◽  
Bone Tumor ◽  
Ewing Sarcoma ◽  
Case Reports ◽  
Case Series ◽  
Biological Explanation

Ewing sarcoma is an aggressive mesenchymal malignancy. It is the second most common bone tumor among children and adolescents and less commonly presents as a soft tissue or primary skin lesion. Cutaneous Ewing sarcoma has only been reported in case reports and case series. In this article, we describe a 12-year-old Hispanic female cured of localized, cutaneous Ewing sarcoma (pT1aN0M0) at the 40-month follow-up following surgical resection and adjuvant chemotherapy according to the COG AEWS1031 protocol for Ewing sarcoma of the bone. To our knowledge, this is the first article to provide a potential biological explanation for the differences in the prognosis of Ewing sarcoma of the bone, soft tissue, and skin.

Multicenter Phase II Study of Irinotecan, Cisplatin, and Bevacizumab in Patients With Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

2006 ◽  
Vol 24 (33) ◽  
pp. 5201-5206 ◽  
Author(s):  
Manish A. Shah ◽  
Ramesh K. Ramanathan ◽  
David H. Ilson ◽  
Alissa Levnor ◽  
David D'Adamo ◽  
...  
Keyword(s):  
Response Rate ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Patient Characteristics ◽  
Time To Progression ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Upper Gastrointestinal Bleed ◽  
Grade 3

Purpose Bevacizumab improves survival in several solid tumor malignancies when combined with chemotherapy. We evaluated the efficacy and safety of the addition of bevacizumab to chemotherapy in the treatment of gastric and gastroesophageal junction (GEJ) adenocarcinoma. Patients and Methods Forty-seven patients with metastatic or unresectable gastric/GEJ adenocarcinoma were treated with bevacizumab 15 mg/kg on day 1, irinotecan 65 mg/m2, and cisplatin 30 mg/m2 on days 1 and 8, every 21 days. The primary end point was to demonstrate a 50% improvement in time to progression over historical values. Secondary end points included safety, response, and survival. Results Patient characteristics were as follows: median age 59 years (range, 25 to 75); Karnofsky performance status 90% (70% to 100%); male:female, 34:13; and gastric/GEJ, 24:23. With a median follow-up of 12.2 months, median time to progression was 8.3 months (95% CI, 5.5 to 9.9 months). In 34 patients with measurable disease, the overall response rate was 65% (95% CI, 46% to 80%). Median survival was 12.3 months (95% CI, 11.3 to 17.2 months). We observed no increase in chemotherapy related toxicity. Possible bevacizumab-related toxicity included a 28% incidence of grade 3 hypertension, two patients with a gastric perforation and one patient with a near perforation (6%), and one patient with a myocardial infarction (2%). Grade 3 to 4 thromboembolic events occurred in 25% of patients. Although the primary tumor was unresected in 40 patients, we observed only one patient with a significant upper gastrointestinal bleed. Conclusion Bevacizumab can be safely given with chemotherapy even with primary gastric and GEJ tumors in place. The response rate, time to disease progression (TTP), and overall survival are encouraging, with TTP improved over historical controls by 75%. Further development of bevacizumab in gastric and GEJ cancers is warranted.

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