scholarly journals Two-fraction high-dose-rate brachytherapy within a single day combined with external beam radiotherapy for prostate cancer: single institution experience and outcomes

2016 ◽  
Vol 57 (3) ◽  
pp. 280-287 ◽  
Author(s):  
Junyang Liu ◽  
Motoki Kaidu ◽  
Ryuta Sasamoto ◽  
Fumio Ayukawa ◽  
Nobuko Yamana ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Groups ◽  
High Dose Rate ◽  
High Dose ◽  
Single Institution ◽  
Risk Patients ◽  
Prescription Dose ◽  
Grade 3 ◽  
3D Crt

Abstract We investigated the outcomes of treatment for patients with localized prostate cancer (PCa) treated with 3D conformal radiation therapy (3D-CRT) followed by two-fraction high-dose-rate brachytherapy within a single day (2-fr.-HDR-BT/day) at a single institution. A total of 156 consecutive Asian males (median age, 67 years) were enrolled. To compare our findings with those of other studies, we analyzed our results using the D'Amico classification, assigning the patients to low- ( n = 5; 3.2%), intermediate- ( n = 36; 23.1%) and high-risk ( n = 115; 73.7%) groups (Stage T3 PCa patients were classified as high-risk). One patient in the D'Amico low-risk group (20%), 13 intermediate-risk patients (36.1%) and 99 high-risk patients (86.1%) underwent androgen deprivation therapy. We administered a prescription dose of 39 Gy in 13 fractions of 3D-CRT combined with 18 Gy of HDR-BT in two 9-Gy fractions delivered within a single day. We did not distinguish between risk groups in determining the prescription dose. The median follow-up period was 38 months. Of the 156 patients, one died from primary disease and five died from other diseases. The 3-year overall survival (OS) rates were 100%, 100% and 93.7%, and the 3-year ‘biochemical no evidence of disease (bNED)’ rates were 100%, 100% and 96.9% for the D'Amico low-, intermediate- and high-risk groups, respectively. No patient developed ≥ Grade 3 early toxicity. The Grade 3 late genitourinary toxicity rate was 2.6%, and no ≥ Grade 3 late gastrointestinal toxicity occurred. The efficacy and safety of this study were satisfactory, and longer-term follow-up is necessary.

scholarly journals Conformal radiotherapy plus high dose rate brachytherapy prostate boost in patients with intermediate and high risk prostate cancer: our experience in Asian males

2012 ◽  
Vol 11 (4) ◽  
pp. 257-270
Author(s):  
Mutahir A. Tunio ◽  
Altaf Hashmi ◽  
Amjad Sattar ◽  
Rehan Mohsin ◽  
Shoukat Ali ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
High Dose Rate ◽  
High Dose ◽  
Free Survival ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Post Radiation ◽  
Grade 3 ◽  
3D Crt

AbstractPurpose: Recent studies have shown increased prostate cancer control rates with radiation dose escalation. Herein the experience of dose escalation by high dose rate brachytherapy (HDR-BT) adjunct to the three-dimensional conformal radiation therapy (3D-CRT) for prostate cancer is presented.Patients and methods: During the period between August 2005 and July 2007, patients with intermediate and high risk prostate cancer were treated with 3D-CRT of dose 46Gy ÷ 23 fractions to whole pelvis followed by: Arm A (102 patients): prostate boost with HDR-BT 14 Gy × 2 sessions and Arm B (103 patients): prostate boost via 3D-CRT of dose 26 Gy ÷ 13 fractions. Primary objectives were overall survival (OS), distant metastases free survival (DMFS) and PSA progression free survival (PPFS) rates. Secondary objectives were the toxicity profile and post-radiation histopathological response.Results: At median follow up of 3.5 years, PPFS, DMFS and OS rates were; 97.8% versus 89.0% (p = 0.009), 98.1% versus 93.6% (p = 0.13) and 98.8% versus 91.6% (p = 0.24) in Arm A and Arm B. respectively. Grade 3 or 4 delayed genitourinary toxicities occurred in 2% and 4.8% of patients in Arm A and Arm B, respectively. Delayed grade 3 and 4 gastrointestinal toxicities were seen in 2% and 3.9% of patients in Arm A and Arm B, respectively. The post-radiation prostate biopsies were negative in 14/17(82.3%) and 9/15 (60%) in Arm A and Arm B, respectively.Conclusion: 3D-CRT combined with HDR-BT resulted in better PPFS and lower morbidity than 3DCRT alone for intermediate and high risk prostate cancer.

Combined treatment image guided-intensity modulated radiotherapy (IG-IMRT) plus high-dose rate brachytherapy (HDR) and hormonotherapy (HT) as treatment for high-risk prostate cancer: Five-year result of a phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15571-15571
Author(s):  
B. Guix ◽  
J. Bartrina ◽  
I. Henriquez ◽  
R. Serrate ◽  
P. Palombo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Dose Rate ◽  
Late Effects ◽  
High Dose Rate ◽  
High Dose ◽  
Group 2 ◽  
Grade 3 ◽  
Group 1

15571 Background: To report early and late toxicity and preliminary biochemical outcome in 345 patients with high-risk (Gleason >=7; PSA>20 or T2c-T3) clinically localized prostate cancer treated with combined high-dose-rate brachytherapy and IMRT (IMRT-HDR) to the prostate and seminal vesicles with 24–36 months of hormononal treatment (goserelin+bicalutamide) (HT). Methods: Between 12/1999 and 10/2003, 345 patients with PSA>20, Gleason score>6 and/or T2c-T3 N0 M0 prostate cancer were treated with IG-IMRT followed by HDR implant to the prostate and HT. Patients were randomly assigned to receive HT for 24 (group 1, 172 patients) or 36 months (group 2, 173 patients). Acute and late toxicities were scored by the EORTC/RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life was done. PSA failure was defined as nadir +2.0 ng/ml. Results: All patients completed treatment. One patient included in the group 1 and none of the group 2 experienced grade 3 rectal toxicity (rectal ulcer). Seven patients in each group (4.0%) developed acute Grade 2 urinary symptoms, and none experienced urinary retention. No patient (0%) developed Grade 4 rectal complications or grade 3 or 4 urinary complications. With a median follow-up of 44 months, the 5-year actuarial PSA relapse-free survival rates for the whole group of patients was 95.7 %. No statistical differences between group 1 and 2 patients were found. Conclusions: High-dose IG-IMRT+HDR and HT was a safe and effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute and late rectal and urinary complications were significantly low, compared with what has been observed with high-dose conventional, 3D-conformal or IMRT-only. Short-term PSA control rates seem to be at least comparable to those achieved with 3D-EBRT or IMRT. Both treatment regimes were very effective. Longer follow-up is needed to know if better PSA control rate are achieved with longer HT. No significant financial relationships to disclose.

scholarly journals High-Dose-Rate Brachytherapy as Monotherapy for Low- and Intermediate-Risk Prostate Cancer. Oncological Outcomes After a Median 15-Year Follow-Up

2021 ◽  
Vol 11 ◽  
Author(s):  
Manuel Behmueller ◽  
Nikolaos Tselis ◽  
Nikolaos Zamboglou ◽  
Eleni Zoga ◽  
Dimos Baltas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Dose Rate ◽  
High Dose Rate ◽  
High Dose ◽  
Intermediate Risk ◽  
Biochemical Relapse ◽  
Free Survival ◽  
Grade 3

IntroductionTo evaluate the oncological outcome of high dose rate (HDR) brachytherapy (BRT) as monotherapy for clinically localised prostate cancer (PCA).Material and MethodsBetween January 2002 and February 2004, 141 consecutive patients with clinically localised PCA were treated with HDR-BRT monotherapy. The cohort comprised 103 (73%) low-, 32 (22.7%) intermediate- and 6 (4.3%) high risk patients according to D’Amico classification or 104 (73.8%) low-, 24 (17.0%) intermediate favourable-, 12 (8.5%) intermediate unfavourable- and one (0.7%) very high risk patient according to National Comprehensive Cancer Network (NCCN) one. Patients received four fractions of 9.5 Gy delivered within a single implant up to a total physical dose of 38 Gy. Catheter-implantation was transrectal ultrasound-based whereas treatment planning CT-based. Thirty-three patients (23.4%) received ADT neoadjuvantly and continued concurrently with BRT. Biochemical relapse-free survival (BRFS) was defined according to the Phoenix Consensus Criteria and genitourinary (GU)/gastrointestinal (GI) toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 5.0.ResultsMedian age at treatment and median follow-up time was 67.2 and 15.2 years, respectively. Twenty-three (16.3%) patients experienced a biochemical relapse and 5 (3.5%) developed distant metastases, with only one patient dying of PCA. The BRFS was 85.1% at 15 years and 78.7% at 18 years. The corresponding overall survival, metastases-free survival, and prostate cancer specific mortality at 15- and 18-years was 73.9%/59.1%, 98.3%/90.6%, and 100%/98.5% respectively. Late grade 3 GI and GU toxicity was 4.2% and 5.6% respectively. Erectile dysfunction grade 3 was reported by 27 (19%) patients. From the prognostic factors evaluated, tumor stage (≤T2b compared to ≥T2c) along with the risk group (low-intermediate vs. high) when using the D’Amico classification but not when the NCCN one was taken into account, correlated significantly with BRFS.ConclusionOur long-term results confirm HDR-BRT to be a safe and effective monotherapeutic treatment modality for low- and intermediate risk PCA.

scholarly journals Clinical Trials in High-Risk Medulloblastoma: Evolution of the SIOP-Europe HR-MB Trial

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 374
Author(s):  
Simon Bailey ◽  
Nicolas André ◽  
Lorenza Gandola ◽  
Maura Massimino ◽  
Stefan Rutkowski ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
High Risk ◽  
Disease Risk ◽  
Risk Groups ◽  
Randomised Clinical Trial ◽  
Paediatric Oncology ◽  
High Dose ◽  
The Status ◽  
Risk Patients

Medulloblastoma patients receive adapted therapies stratified according to their risk-profile. Favourable, standard, and high disease-risk groups are each defined by the status of clinical and pathological risk factors, alongside an evolving repertoire of diagnostic and prognostic biomarkers. Medulloblastoma clinical trials in Europe are coordinated by the International Society for Paediatric Oncology (SIOP-Europe) brain tumour group. Favourable and standard-risk patients are eligible for the SIOP-PNET5-MB clinical trial protocol. In contrast, therapies for high-risk disease worldwide have, to date, encompassed a range of different treatment philosophies, with no clear consensus on approach. Higher radiotherapy doses are typically deployed, delivered either conventionally or in hyper-fractionated/accelerated regimens. Similarly, both standard and high-dose chemotherapies were assessed. However, trials to date in high-risk medulloblastoma have commonly been institutional or national, based on modest cohort sizes, and have not evaluated the relative performance of different strategies in a randomised fashion. We describe the concepts and design of the SIOP-E high-risk medulloblastoma clinical trial (SIOP-HR-MB), the first international biomarker-driven, randomised, clinical trial for high-risk medulloblastoma. SIOP-HR-MB is programmed to recruit >800 patients in 16 countries across Europe; its primary objectives are to assess the relative efficacies of the alternative established regimens. The HR-MB patient population is molecularly and clinically defined, and upfront assessments incorporate a standardised central review of molecular pathology, radiology, and radiotherapy quality assurance. Secondary objectives include the assessment of (i) novel therapies within an upfront ‘window’ and (ii) therapy-associated neuropsychology, toxicity, and late effects, alongside (iii) the collection of materials for comprehensive integrated studies of biological determinants within the SIOP-HR-MB cohort.

scholarly journals Risk-adapted survival benefit of IMRT in early-stage NKTCL: a multicenter study from the China Lymphoma Collaborative Group

2018 ◽  
Vol 2 (18) ◽  
pp. 2369-2377 ◽  
Author(s):  
Tao Wu ◽  
Yong Yang ◽  
Su-Yu Zhu ◽  
Mei Shi ◽  
Hang Su ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
High Risk ◽  
Survival Benefit ◽  
Early Stage ◽  
Low Risk ◽  
Collaborative Group ◽  
High Dose ◽  
Conformal Radiation Therapy ◽  
Risk Patients ◽  
3D Crt

Abstract This study evaluated the survival benefit of intensity-modulated radiation therapy (IMRT) compared with 3-dimension conformal radiation therapy (3D-CRT) in a large national cohort of patients with early-stage extranodal nasal-type natural killer/T-cell lymphoma (NKTCL). This retrospective study reviewed patients with early-stage NKTCL treated with high-dose radiation therapy (RT; ≥45 Gy) at 16 Chinese institutions. Patients were stratified into 1 of 4 risk groups based on the number of risk factors: low risk (no factors), intermediate-low risk (1 factor), intermediate-high risk (2 factors), and high-risk (3-5 factors). Of the 1691 patients, 981 (58%) received IMRT, and 710 (42%) received 3D-CRT. Unadjusted 5-year overall survival (OS) and progression-free survival (PFS) were 75.9% and 67.6%, respectively, for IMRT compared with 68.9% (P = .004) and 58.2% (P < .001), respectively, for 3D-CRT. After propensity score match and multivariable analyses to account for confounding factors, IMRT remained significantly associated with improved OS and PFS. The OS and PFS benefits of IMRT persisted in patients treated with modern chemotherapy regimens. Compared with 3D-CRT, IMRT significantly improved OS and PFS for high-risk and intermediate-high–risk patients but provided limited benefits for low-risk or intermediate-low–risk patients. A risk-adapted survival benefit profile of IMRT can be used to select patients and make treatment decisions.

Results of an Exploratory Study of Oral (po) and Intravenous (iv) Clofarabine in Patients with Myelodysplastic Syndrome.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1455-1455 ◽  
Author(s):  
Stefan Faderl ◽  
Guillermo Garcia-Manero ◽  
Varsha Gandhi ◽  
Farhad Ravandi ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
High Risk ◽  
Optimal Dose ◽  
Risk Groups ◽  
Median Number ◽  
High Dose ◽  
Two Phase ◽  
Phase Ii Studies ◽  
Grade 3 ◽  
Febrile Episodes ◽  
Elevated Transaminases

Abstract Clofarabine (CLO) is an adenosine nucleoside analog with activity in adult acute myeloid leukemia (AML). Its activity in MDS is less well defined. To evaluate the activity and safety of CLO in MDS we designed two phase II studies with iv CLO and po CLO, respectively. Pts were eligible if they had MDS with ≥ 5% blasts, fell into IPSS intermediate-2 and high-risk groups, or had CMML. No prior intensive chemotherapy or high-dose cytarabine was allowed. Hematopoietic growth factor support was permitted. In the iv study pts were adaptively randomized to receive CLO 15 or 30 mg/m2 iv daily x 5 every 4–6 weeks. The second study used a starting dose of CLO 40 mg/m2 orally daily x 5 every 4–6 weeks (assuming oral bioavailability about 50%), which was then decreased to 30 mg/m2 orally daily x 5. Thirty pts (18 RAEB, 6 RAEB-T, 6 CMML) have been treated. Assignment by IPSS for RAEB and RAEB-T pts: 10 high-risk, 10 intermediate-2, and 4 intermediate-1. Fifteen pts received iv CLO and 15 po CLO. Median age was 68 yrs (range 57–86). Median number of prior therapies was 1 (0–4). Twenty (67%) pts received prior decitabine or azacitidine. Karyotype was abnormal in 24 (80%) pts, including 10 pts with −5/−7 abnormalities. Responses were determined according to International Working Group criteria (IWG). Twenty-seven pts were evaluable for response (2 pts too early, one refused further treatment on day 4 of first course). Eleven (41%) pts responded [7 (26%) CR, 2 (7%) HI, 2 (7%) clinical benefit (CB)] (see table). Response (%) Route Dose (mg/m2) N CR HI CB po 40 6 - - 1 (17) 30 6 1(17) 2 (33) 1 (17) iv 30 6 2 (33) - - 15 9 4 (44) - - Response by IPSS: 67% intermediate-1, 44% intermediate-2, 40% high. Twenty-seven pts are evaluable for toxicities. Grade ≥ 3 toxicities occurred in 8 of 13 pts on iv CLO (rash, hyperbilirubinemia, elevated transaminases, elevations of creatinine, acute renal failure) and 4 of 14 pts with po CLO (rash, hyperbilirubinemia, elevated transaminases). Myelosuppression resulting in febrile episodes and hospitalizations with both iv and po CLO was ubiquitous, but prolonged myelosuppression (> 42 days) was rare. In summary, CLO has activity in pts with higher-risk MDS. The optimal dose and schedule for po and iv CLO have not been defined yet. Lower doses of CLO are associated with responses. Correlative PK studies may help to provide further support for optimal dose and route of administration of CLO in pts with MDS.

Survival in Patients with Newly Diagnosed Myeloma Undergoing Therapy with Lenalidomide and Dexamethasone: Impact of High-Risk Cytogenetic Risk Status on Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 95-95 ◽  
Author(s):  
Prashant Kapoor ◽  
Shaji Kumar ◽  
Rafael Fonseca ◽  
Martha Q. Lacy ◽  
Thomas E Witzig ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Plasma Cell ◽  
Risk Groups ◽  
Newly Diagnosed ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Impact ◽  
Standard Risk

Abstract Background: Multiple myeloma (MM) is a heterogeneous disease with very divergent outcomes that are dictated in a large part by specific cytogenetic abnormalities, as well as other prognostic factors such as the proliferative rate of marrow plasma cells. Prognostic systems incorporating these factors have shown clinical utility in identifying high-risk patients, and are increasingly being utilized for treatment decision-making. However, the prognostic relevance of these factors may change with the application of novel therapies. The objective of this study was to determine the impact of risk-stratification (incorporating plasma cell metaphase cytogenetics, interphase fluorescent in-situ hybridization (FISH) and the slide-based plasma cell labeling index (PCLI)) in a cohort of patients with newly diagnosed MM treated initially with lenalidomide + dexamethasone (Rev-Dex). Methods: From March 2004 to November 2007, 100 consecutive patients treated with Rev (25mg/day) on days 1 through 21 of a 4-week cycle in combination with dexamethasone as initial therapy for newly diagnosed myeloma, were identified. High-risk MM was defined as presence of any one or more of the following: hypodiploidy, monoallelic loss of chromosome 13 or its long arm (by metaphase cytogenetics only), deletion of p53 (locus 17p13) or PCLI ≥ 3% or immunoglobulin heavy chain (IgH) translocations, t(4;14) (p16.3;q32) or t(14;16)(q32;q23) on FISH. PFS and OS survival estimates were created using the Kaplan Meier method, and compared by log-rank tests. Results: The median estimated follow-up of the entire cohort (N=100) was 36 months. The median PFS was 31 months; the median OS has not been reached. The 2- and 3-year OS estimates were 93% and 83%, respectively. 16% patients were deemed high-risk by at least one of the 3 tests (cytogenetics, FISH or PCLI). Response rates (PR or better) were 81% versus 89% in the high-risk and standard risk groups, respectively, P=NS; corresponding values for CR plus VGPR rates were 38% and 45% respectively. The median PFS was 18.5 months in high-risk patients compared to 37 months in the standard-risk patients (n=84), P<0.001(Figure). Corresponding values for TTP were 18.5 months and 36.5 months, respectively, P=<0.001. OS was not statistically significant between the two groups; 92% 2-year OS was noted in both the groups. Overall, 95 patients had at least one of the 3 tests to determine risk, while 55 patients could be adequately stratified based on the availability of all the 3 tests, or at least one test result that led to their inclusion in the high-risk category. The significant difference in PFS persisted even when the analysis was restricted to the 55 patients classified using this stringent criterion; 18.5 months vs. 36.5 months in the high-risk and standard- risk groups respectively; P<0.001. In a separate analysis, patients who underwent SCT before the disease progression were censored on the date of SCT to negate its effect, and PFS was still inferior in the high-risk group (p=0.002). Conclusion: The TTP and PFS of high-risk MM patients are inferior to that of the standard-risk patients treated with Rev-Dex, indicating that the current genetic and proliferation-based risk-stratification model remains prognostic with novel therapy. However, the TTP, PFS, and OS obtained in high-risk patients treated with Rev-Dex in this study is comparable to overall results in all myeloma patients reported in recent phase III trials. In addition, no significant impact of high-risk features on OS is apparent so far. Longer follow-up is needed to determine the impact of risk stratification on the OS of patients treated with Rev-Dex. Figure Figure

Efficacy and Toxicity of Rituximab and Brief Duration, High Intensity Chemotherapy with Filgrastim Support for Burkitt or Burkitt – Like Leukemia/Lymphoma: Cancer and Leukemia Group B (Calgb) Study 10002

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 858-858 ◽  
Author(s):  
David A. Rizzieri ◽  
Jeffrey L Johnson ◽  
John C. Byrd ◽  
Gerard Lozanski ◽  
Bayard L. Powell ◽  
...  
Keyword(s):  
High Risk ◽  
High Intensity ◽  
International Prognostic Index ◽  
Tumor Lysis Syndrome ◽  
Prognostic Index ◽  
Adult Patients ◽  
Term Survival ◽  
Risk Patients ◽  
Grade 3

Abstract Abstract 858 Prior studies have shown that combination chemotherapy using high doses of antimetabolites and alkylating agents over a short duration is effective treatment for Burkitt leukemia and lymphoma. Adults able to tolerate this therapy have had > 50% long term survival, although those with higher risk by the International Prognostic Index (IPI) have had inferior outcomes. Between 5/2002 and 9/2009, we enrolled 105 adults (19-79 yrs old) with untreated Burkitt leukemia/lymphoma onto a phase II study of a high intensity chemo-immunotherapy regimen to assess the benefit of adding rituximab plus growth factor support to the intensive chemotherapy regimen developed in CALGB 9251 and evaluated patterns of relapse when prophylactic cranial irradiation was not given. All subjects were HIV negative and had serum creatinine and bilirubin ≤1.5 × upper limit. Complete data are available on 105 patients for toxicity and 103 patients for efficacy. Methods: Treatment began with cyclophosphamide (CY) 200 mg/m2 × 5 days and prednisone 60 mg/m2 × 7 days. Cycle 2 was started on Day 8 after entry. Cycles 2, 4, and 6 consisted of ifosfamide 800 mg/m2 on days 1–5, methotrexate (MTX) 1.5 g/m2 infused over day 1 with leucovorin rescue, vincristine (VCR) 2 mg day 1, Ara-C 1 gm/m2 days 4 and 5, VP-16 80 mg/m2 days 4 and 5, and dexamethasone 10 mg/m2 on days 1–5. Cycles 3, 5, and 7 included the same doses of MTX, VCR, and dexamethasone, with CY 200 mg/m2 IV on days 1–5 and doxorubicin 25 mg/m2 days 4 and 5. Cycles were delivered every 21 days if blood counts had recovered. Filgrastim was given at 5μg/kg/day SC beginning day 7 of each cycle and continuing until the absolute neutrophil count recovered to > 5000/μL. Rituximab was initiated during cycle 2 on day 8 at 50 mg/m2 and on days 10 and 12 at 375 mg/m2. During cycles 3 through 7, rituximab was infused only on day 8 of each course at 375 mg/m2. Central nervous system (CNS) prophylaxis consisted of triple intrathecal therapy on day 1 of cycles 2–7 (6 total doses). Results: 27% of patients were ≥60 years old; 70% were male; 46% had intermediate or high risk disease by the IPI (Table). Overall, 75 of 105 subjects completed all 7 planned courses of therapy. 82% attained a complete response (CR), and 87% of these remain in CR at last follow up. 7% had a partial response. With median follow up of survivors of 3.2 years, 2 year event free survival (EFS) and overall survival (OS) were 77% and 79%, respectively, with a trend favoring those <60 years old (87% and 87%, respectively). There were clear differences in outcome based on IPI score with 2 year EFS and OS for low risk patients of 90% and 92% versus 55% and 55% for high risk patients, respectively (Figure). This protocol did not use prophylactic CNS radiation, and 4 pts had documented CNS relapses; 2 had intermediate and 1 high IPI disease; the 4th was unknown. Relapse after 2 years was rare. 7 subjects (6.8%) died from treatment related causes (1 CNS bleed, 4 infections, 2 respiratory failure). Nearly all subjects experienced the anticipated severe hematologic toxicities. The most common grade 3 and 4 non-hematologic toxicities included stomatitis/upper GI toxicity (∼ 66%), nausea/vomiting (20%), fatigue (26%), rash or erythema multiforme (10%), diarrhea (10%), pulmonary or CNS bleeding (11%), clinically documented infections (72%), neurologic disturbances (8%), and dyspnea (10%). 8 pts (8%) had tumor lysis syndrome (all grade 3). Conclusion: This regimen provides a high rate of durable remissions in adult patients with a manageable side effect profile. Chemoimmunotherapy should be the standard for adult patients with Burkitt leukemia/lymphoma. Disclosures: Off Label Use: Rituximab for use in Burkitt's. Cheson:Genentech: Consultancy.

Alemtuzumab Plus Oral Dexamethasone, Followed by Alemtuzumab Maintenance or Allogeneic Transplantation in Ultra High-Risk CLL: Interim Analysis of a Phase II Study of the GCLLSG and fcgcll/MW

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2854-2854 ◽  
Author(s):  
Stephan Stilgenbauer ◽  
Florence Cymbalista ◽  
Véronique Leblond ◽  
Alain Delmer ◽  
Dirk Winkler ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Response Rates ◽  
Long Term Results ◽  
High Dose ◽  
Significant Difference ◽  
Ultra High Risk ◽  
Grade 3 ◽  
The Impact

Abstract Abstract 2854 Alemtuzumab (A) proved to be efficacious in CLL patients (pts) with very poor prognosis, either due to fludarabine (F) refractoriness or due to unfavorable cytogenetics (17p-). However, rate and duration of remissions still remain unsatisfactory. Therefore, the French and German CLL study groups jointly embarked on this trial, trying to achieve higher overall response rates (ORR) by adding high-dose dexamethasone (D) to A and, simultaneously, investigating the consolidation effect of prolonged A maintenance or allogeneic stem-cell transplantation (allo-SCT), respectively. Induction treatment consisted of subcutaneous A 30 mg weekly × 3 for 28 days, combined with oral D 40 mg on days 1–4 and 15–18, and prophylactic pegfilgrastim 6 mg on days 1 and 15. Depending on the remission status, pts were treated for up to 12 weeks. If CR was documented at 4 or 8 weeks, or at least SD was achieved at 12 weeks, consolidation was scheduled with either allo-SCT or A maintenance with 30 mg every 14 days for up to 2 years (y), at the discretion of pt and physician. Between January 2008 and July 2011, 124 pts were recruited at 26 centers, 120 of whom were eligible. Pts were generally subdivided into three cohorts: 55 pts were refractory (i.e. no response or relapse within 6 months) to regimens containing F or a similar drug (i.e. pentostatin, cladribine, bendamustine). Non-refractory pts all exhibited 17p- and had either untreated (n=39) or relapsed CLL (n = 26) requiring therapy. The median age was high with 66/64/66 y in 17p- 1st line, 17p- relapse, and F-refractory pts, respectively. The three cohorts had 46/54/75% Binet C disease, 41/35/27% B symptoms, 38/42/53% reduced performance status (ECOG 1/2), median thymidine kinase levels of 35/49/24 U/L, median ß2MG levels of 3.8/5.5/4.6 mg/L, and IGHV was unmutated in 89/96/87%. In the F-refractory group, 53% exhibited 17p deletion and 22% had 11q deletion. Pretreated patients had received a median of 3 (F-refractory) or 2 prior lines (17p- relapse). 5 pts had previously undergone autologous and 1 pt allo-SCT. Treatment and efficacy data are currently available for 87 pts who completed induction therapy :17p- 1st-line (n=30), 17p- relapse (n=17), and F-refractory (n=40). Of these, 80/53/55% received the full induction of 12 weeks. ORR (best observed status) was generally high with 97/76/70%. CR was achieved in 20/0/5%. After a median follow-up of 11.8 months (mo), median progression-free survival (PFS) was 16.9/10.4/8.4 mo. Deaths are recorded in 13/27/36% of pts, with median overall survival (OS) not yet reached (>24 mo) in the 17p- 1st line group, and 15/12 mo in 17p- relapse/F-refractory pts. Consolidation treatment was performed as maintenance A (median duration 32 weeks, range 2 – 89) in 34%, and allo-SCT in 30%, with a median age of 66 and 61 y in these subgroups. The main reasons for going off-study without consolidation were death due to infection (14%, n=11, of these 6 without response, and 10 in the F-refractory cohort), CLL progression (12%), and other toxicity (5%). Among the 28 pts not receiving consolidation, there were 19 (68%) deaths, 15 of them in the F-refractory cohort. When comparing A maintenance and allo-SCT for consolidation, there were 9 (35%) and 7 (30%) PD events, respectively and there was so far no significant difference in PFS (median 17 mo in both groups) or OS. During induction, grade 3/4 hematotoxicity consisted of anemia in 28%, neutropenia in 47%, and thrombopenia in 44%. Grade 3/4 non-CMV infection occurred in 29% of 17p- 1st-line, 15% of 17p- relapsed, and 56% of F-refractory pts. CMV reactivation was observed in 54/25/40%, without severe sequelae recorded. During A maintenance, grade 3/4 toxicity consisted of neutropenia in 39% pts and thrombopenia in 4% pts with 6 SAEs (ITP, diarrhea, infection, erythema, tachycardia, and thrombosis). Conclusions: The combination of A and D shows high response rates in ultra high-risk CLL, with promising preliminary findings for PFS and OS, despite the high median age of the pts. The results compare favorably to ORR/CR of 68%/5%, and median PFS of 11.3 mo in the 17p- subgroup of the CLL8 study treated with FCR, consisting of younger pts (median 61 y). In F-refractory CLL however, when compared to the preceding CLL2H study with single agent A, the improved initial response by adding dexamethasone does not seem to translate into improved long-term results. More mature follow-up is needed, especially with respect to the impact of allo-SCT. Disclosures: Stilgenbauer: Amgen: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding. Off Label Use: Alemtuzumab in 1st line CLL treatment. Cymbalista:Roche (d) Mundipharma (e) Genzyme (e): Honoraria, Research Funding. Hinke:WiSP (CRO): Employment.

Effect of gene expression profile (GEP) testing on clinical management in 19% of consecutively treated patients with stage IB/IIA melanoma at a single institution.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21080-e21080
Author(s):  
Lynn Thacher Dengel ◽  
Alexandra W. Hickman ◽  
Craig L. Slingluff
Keyword(s):  
High Risk ◽  
Distant Metastases ◽  
Risk Scores ◽  
Inclusion Criteria ◽  
Single Institution ◽  
Stage Ib ◽  
Risk Result ◽  
Risk Patients ◽  
Biopsy Methods

e21080 Background: A 31-GEP test is predictive of metastasis in cutaneous melanoma. We hypothesized that GEP testing would “upgrade” surveillance to routine imaging in at least 16% of stage IB/IIA patients, similar to the upgrade rate from sentinel node biopsy. Methods: A GEP score was obtained for consecutive patients with Stage IB/IIA melanoma treated between 6/2014-6/2016. A retrospective review of a prospectively collected database was performed. Results: 67 patients with Stage IB/IIA melanoma met inclusion criteria. In four cases, a GEP result was not available. Of the 63 tested cases, 68% were Stage IB (N = 43), and 32% were Stage IIA (N = 20). A high-risk result was seen in 12% of stage IB (5/43) and 42% of stage IIA (8/19) patients. Insurance denied coverage of scans in 1/13 patients with a high-risk GEP result. The remaining 12 Stage IB/IIA patients with high-risk scores were “upgraded” to high-intensity surveillance. With a median follow-up of 14 months, 1/13 patients with a high-risk GEP result developed distant metastases 21 months after diagnosis of a Stage IIA melanoma. Conclusions: Results from this retrospective single institution study show that GEP testing altered patient management in 19% of Stage IB/IIA patients. Early detection in 1/13 patients with high-risk scores in this series supports further investigation into stratifying traditionally low-risk patients by GEP testing.

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