Sarcoligo: Impact of local ablative treatment of oligometastatic sarcomas on overall survival.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10042-10042
Author(s):  
Juliette Thariat ◽  
Laurence Moureau-Zabotto ◽  
Nicolas Penel ◽  
Antoine Italiano ◽  
Jacques-Olivier Bay ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Metastases ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Locoregional Treatment ◽  
Metastatic Sites ◽  
The Impact

10042 Background: 40-50% of sarcomas become metastatic. Median survival of metastatic patients has improved over time. The probably multifactorial reasons for such improvement are not fully clear. Noteworthy, for patients with a controlled primary and a limited number of lung metastases, complete resection of their metastases yields survival rates of up to 40% at three years. Advances in surgery, radiotherapy and radiofrequency have fostered the use of local treatments for various metastatic sites (lung, liver, spine...). Methods: A multicentric retrospective study of the Groupe Sarcome Francais (GSF-GETO); approved by the nationally-review board and ethical committee, was conducted to assess the impact of local ablative treatment on overall survival. Patients who had had oligometastases (any site, 1-5 synchronous metastases) at diagnostic or during the course of disease between 2000 and 2010 were included. Results: Median age of the 243 oligometastatic sarcoma patients was 53 years-old (11-86). Patients had grade I, II and III in 7.5%, 29.6% and 63.3% of cases, respectively with various histologies. 69% of patients underwent local ablative treatment of metastases. Median follow-up was 59 months (4-212) for living patients. Median overall survival was 51 months (1-348). On univariate analysis, grade, histology, absence of chemotherapy, local ablative treatment (surgery, irradiation, radiofrequency or chemoembolisation) correlated with survival but not age or site of oligometastasis. On multivariate analyses, grade (hazard ratio HR 0.12 [CI95 0.3-0.6]) and local ablative treatment (HR 3.8 [CI95 2.1-7.1]) remained significant. Conclusions: Local ablative treatment of metastases is associated with better survival in sarcoma patients with oligometastatic disease. The role of the locoregional treatment of metastases and its impact on quality of life should be assessed prospectively.

Exploring the scope of homoeopathy in combating the unfortunate consequences of post-COVID-19 survivors based on non-COVID conditions: a narrative review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ashish Kumar Dixit ◽  
Nibha Giri ◽  
Shishir Singh
Keyword(s):  
Chronic Fatigue ◽  
Cardiac Insufficiency ◽  
Medical Database ◽  
Fatigue Syndrome ◽  
Tract Infections ◽  
The Impact

Abstract Objectives The long-term consequences of COVID-19 survivors care and post-coronavirus infection are not yet well understood. The review aims to see whether homoeopathy can help COVID-19 survivors recover from its consequences and improve their quality of life. Content A systematic search of published articles for post-COVID sequelae and the impact of Homoeopathy were conducted. For the literature search, the major electronic bio-medical database PubMed/MEDLINE was used. In addition, supplementary searches were conducted through the references of those published articles. Summary A total of 113 records were identified of which 61 studies included for this review. Homoeopathy is effective in the treatment of mental disorders including anxiety and depressive disorder (ADD), some research studies have found, although systematic reviews disagree. Likewise, some medical societies denounce homoeopathy for pain management; other literature shows that it can be used to treat pain effectively. Homoeopathy can aid in the treatment of cardiovascular diseases, as Crataegus, a homoeopathic medication, was found to be just as effective as a standard angiotensin-converting enzyme (ACE) inhibitor and diuretic treatment for minor cardiac insufficiency. The outcomes for Chronic Fatigue Syndrome (CFS), Influenza, and Acute Respiratory Tract Infections (ARTIs) are also promising. Outlook Based on the results of homoeopathy in non-COVID conditions, it can be thought of in the management of post-COVID-19 outcomes. Consequently, we propose that while investigating post-COVID-19 patient rehabilitation, homoeopathic management may be included as part of the follow-up route and as much data as possible in the context of homoeopathy should be collected, so that in future, the role of homoeopathy in dealing with it can be better demonstrated.

scholarly journals Long-term follow-up of children with neuroblastoma receiving radiotherapy to metastatic lesions within the German Neuroblastoma Trials NB97 and NB 2004

2020 ◽  
Author(s):  
Danny Jazmati ◽  
Sarina Butzer ◽  
Barbara Hero ◽  
Jerome Doyen ◽  
Dalia Ahmad Khalil ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Primary Tumor ◽  
Secondary Malignancy ◽  
Primary Tumor Site ◽  
Free Survival ◽  
Stage 4 ◽  
Metastatic Sites ◽  
The Impact

Abstract Purpose Neuroblastoma (NB) is the most common extracranial solid malignancy during childhood. Despite a multimodal treatment approach, the prognosis of patients with metastatic NB is not satisfactory. Although radiotherapy (RT) has become an integral part of treatment of the primary tumor, the role of RT in osteomedullary lesions is not well defined. A retrospective analysis was conducted to evaluate the impact of RT for metastatic sites in children with high-risk NB. Methods All patients with stage 4 NB from the prospective, multicenter NB trials NB97 and NB2004 who received RT to metastatic sites during frontline treatment were included in this retrospective analysis. Results A total of 18 children were irradiated with a median dose of 36 Gray (Gy; range 20–45 Gy) to one or more (range 1–3) osteomedullary metastases with or without concomitant RT to the primary tumor site. The median follow-up time was 149 months (range 55–220) in survivors. At 5 years, local relapse-free survival (LRFS) at irradiated metastatic sites and metastases-free survival (MFS) at distant, non-irradiated site rates were 51.4 and 39.9%, respectively. The estimated overall survival (OS) rate at 5 years was 49.4%. No high-grade acute or late toxicity and no secondary malignancy was reported. Conclusion RT to metastases is feasible for patients with stage 4 NB. However, an impact of RT to residual metastatic sites on outcome was not found. Studies with larger cohorts or prospective trials would be desirable in order to elucidate the role of RT for metastases.

The impact of metastasis location on overall survival among patients with renal cell carcinoma.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 621-621
Author(s):  
Devin Patel ◽  
Fady Ghali ◽  
Margaret Meagher ◽  
Margaret Meagher ◽  
Aaron Bradshaw ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Bone Metastases ◽  
Cell Carcinoma ◽  
Metastatic Disease ◽  
Renal Cell ◽  
Lung Metastases ◽  
Univariate Analysis ◽  
The Impact ◽  
Disease Location

621 Background: Current staging guidelines define all patients with metastatic renal cell carcinoma (RCC) as a singular group. We sought to compare the impact of metastatic disease location on overall survival (OS) in patients with RCC. Methods: We queried our institutional database of consecutive patients with metastatic RCC. A confirmatory analysis was performed using the National Cancer Database (NCDB) for cases between 2010 to 2015. Only cases from which all metastatic disease location was known were used. Patients were grouped into having brain or bone metastases, liver or lung metastases or other metastases. From our institutional database, we performed a univariate analysis to determine the impact of metastasis location on OS. From the NCDB, univariable and multivariable Cox proportional hazards and Kaplan-Meier survival analysis with log-rank testing was performed. Multivariable models were adjusted for age, comorbidity, race, gender, and treatment with either palliative care, chemotherapy or immunotherapy. Results: A total of 95 patients were analyzed from our institutional database, with 30 (31.9%) having brain/bone metastases, 20 (21.3%) having lung/liver metastases, and 44 (46.8%) having other site metastases. On univariate analysis, patients with brain/bone metastases had significantly worse OS (HR 1.87; 95% CI 1.01-3.47). However, no significant difference was seen in patients with liver/lung metastases (HR 1.44; 95% CI 0.64-3.27). A total of 25,528 patients met inclusion for our NCDB analysis, of which 12,119 (47.5%) had brain/bone metastases, 10,004 (39.2%) had liver/lung metastases, and 3,405 (13.3%) had other site metastases. On univariate analysis, patients with lung/liver (HR 1.46; 95% CI 1.38-1.53) and patients with bone/brain (HR 1.69; 95% CI 1.60-1.77) had progressively worse OS with non-overlapping confidence intervals. Multivariable analysis again showed that patients with lung/liver disease (HR 1.51; 95% CI 1.43-1.59) and brain/bone disease (HR 1.66; 95% CI 1.60-1.75) had progressively worse OS. Conclusions: Our results highlight the heterogeneity of patients with metastatic renal cell carcinoma. Location of metastatic disease may drive differences in survival.

Cytogenetic Evolution in Patients with IPSS Low and Intermediate-1 Risk. Study from the Spanish Group of Myelodysplastic Syndrome

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4649-4649
Author(s):  
Brayan Marcel Merchán ◽  
Margarita Ortega ◽  
María José Llamas-Poyato ◽  
Montserrat Cortés ◽  
Montserrat Arnan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Population Distribution ◽  
Risk Group ◽  
Univariate Analysis ◽  
Normal Karyotype ◽  
Molecular Diagnostic ◽  
Kaplan Meier ◽  
Cytogenetic Analyses ◽  
The Impact

Abstract Cytogenetic abnormalities (CA) are the most important prognostic factor in MDS patients, nevertheless the incidence of CA at diagnosis is not higher than 50% and even less in lower risk patients. The acquisition of CA (ACA) has recently been reported as a frequent and poor prognostic event in patients with normal karyotype at diagnosis (Jabbour et al 2013). The aim of our study was to analyze in a large cohort of patients the incidence, characteristics, and prognosis of the ACA in patients with low and intermediate-1 IPSS risk at diagnosis. We retrospectively reviewed 254 adult patients from the Spanish Registry of MDS with IPSS low or intermediate-1 risk diagnosed between 1995 and 2013. In total 121 patients had at least two consecutive cytogenetic analyses during the follow up. The main end points were overall survival (OS) and AML evolution (TFS). Cytogenetic analyses were conducted on unstimulated bone marrow cells after culture (24–72 hours). The ISCN 2005 criteria were used for identification of abnormal clones. ACA was defined by structural change or gain in at least 2 metaphases and loss in 3 metaphases as proposed in previous reports. Differences among variables were evaluated by non-parametric tests. OS and TFS were analyzed by Kaplan-Meier curve. The median follow-up was 25 months (0-155). The median age at diagnosis was 71 years (26-87) and 28% of the patients were female. The IPSS risk group was low in 43% and intermediate-1 in 57% of the population. Distribution as the IPSS-R was very low 20%, low 42%, Intermediate-1 30%, poor 6%, and there were no cases with very poor risk. At diagnosis, 34.7% of patients had abnormal karyotype. ACA was detected in 16 patients (13,2%) after a median of 30 months (range, 5-165). The most common ACA identified were trisomy 8 as sole abnormality followed by chromosome 7 abnormalities in in 25% and 12.5% of patients, respectively. Of the 42 patients with CA at diagnosis, 12% developed new ACA while among 79 patients with normal karyotype at diagnosis, 14% developed ACA (p=0,7). The presence of ACA changed the IPSS-R risk group in 14 out 16 patients. Compared with patients without ACA, the presence of ACA was significantly associated with a lower hemoglobin level (Table 1). In univariate analysis, ACA was not apparently associated with a higher incidence of AML evolution as there were 2 out of 16 patients (12,5%) with ACA that developed AML while between the 105 patients without ACA, 11 developed AML (11,5%) (P=NS). At last follow-up, 34 (28%) patients died and the median OS for the entire cohort was 67 months (IC 95% 34-99). In Kaplan-Meier curve, the presence of ACA was associated with lower overall survival (median 67 months (95% CI: 34-99) than patients without ACA (median 140 months (95% CI 36,9.243) (P =0.01). In summary, the present analysis shows that, the ACA occurs in around 13% of cases, which is a lower frequency than previously reported in other series, and it may have impact in overall survival. Future studies should address the impact molecular alterations and somatic point mutations; molecular diagnostic may allow identified patients with higher risk to transformation. Table 1. Hematologic parameters at the time for the cytogenetic control. ACA (n= 16) NO ACA (n=105) P Hb g/dL 9,1 (5.8-11.9) 10,3 (5.6-17.7) 0.04 WBC × 109/L 3,15 (0.7-24.1) 4,1 (0.9-32) 0.85 Pla × 109/L 71 (16-127) 93,5 (4-574) 0.38 Blast × 109/L 6 (1-15) 2.4 (0-19) 0.09 Disclosures Valcárcel: Celgene: Honoraria, Speakers Bureau.

Stereotactic Ablative Radiotherapy for Patients with Unresectable or Medically Inoperable Cholangiocarcinoma

2017 ◽  
Vol 103 (3) ◽  
pp. 236-241 ◽  
Author(s):  
Ming-Yueh Liu ◽  
Cheng-Hsiang Lo ◽  
Chun-Shu Lin ◽  
Hsing-Lung Chao ◽  
Jen-Fu Yang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rates ◽  
Survival Duration ◽  
Stereotactic Ablative Radiotherapy ◽  
Radiation Induced ◽  
Effective Doses ◽  
Bile Duct Tumors ◽  
Overall Survival Rates

Purpose The role of stereotactic ablative radiotherapy (SABR) in patients with unresectable or medically inoperable cholangiocarcinoma remains unclear. We examined the efficacy and safety of SABR in this group of patients. Methods From January 2008 to December 2014, 15 patients with 17 lesions were included in this study. The lesions included 14 intrahepatic, 1 hilar, and 2 distal bile duct tumors. Three patients were classified as medically inoperable because of old age or multiple comorbidities. Tumors measured 0.8-13 cm (median, 3.6 cm). The median prescribed dose was 45 Gy delivered in 5 fractions over 5 consecutive days. Results The median follow-up period for surviving patients was 29.9 months. Objective responses were observed for 10 of 17 tumors (58.8%), including 3 complete responses (17.6%). The median survival duration was 12.6 months, and the 1- and 2-year overall survival rates were 50.3% and 14.4%, respectively. The 1- and 2-year in-field failure-free rates were 61.5% and 30.8%, respectively. For patients with biologically effective doses (BEDs) exceeding 75 Gy10, the 1- and 2-year overall survival rates were 58.3% and 33.3%, respectively, compared to 20.0% and 0%, respectively for those with BEDs lower than 75 Gy10. Radiation-induced liver disease did not develop in any patient. Acute toxicities were generally mild and tolerable. Conclusions Stereotactic ablative radiotherapy could be an alternative treatment for unresectable or medically inoperable cholangiocarcinoma. Further dose escalation may be considered to optimize local control.

Cancer, depression symptoms and quality of life: The role of creativity

2017 ◽  
Vol 41 (S1) ◽  
pp. S470-S471 ◽  
Author(s):  
L. Delpech ◽  
F. Sordes ◽  
J.L. Sudres
Keyword(s):  
Quality Of Life ◽  
Depression Symptoms ◽  
Diagnosis Of Cancer ◽  
Depression Level ◽  
Competing Interest ◽  
Patients Experience ◽  
The Impact

The diagnosis of cancer is associated with the occurrence of psychopathological symptoms, which cause even more difficulties to patients. Scientific research demonstrates that creativity could help increase the general population's quality of life and regulate their negative emotions, but only a few studies are available on the link between creativity and the regulation of patients’ respective experience. This study aims at (1) measuring the impact of creativity on the patient's level of depression and quality of life and (2) evaluating the psychopathological profile of the creative person. Thirty-five subjects undergoing chemotherapy treatment (age: 61 + 11) took part in this study. The experimental protocol is composed of creativity, depression and QoL tests. The results show that creativity is negatively correlated with depression level and positively with QoL (r = −45; P = <.05 and r=.54; P = <.01 respectively). The linear regressions show that creativity is a variable, which predicts a high QoL (F = 13.83; P=.001). Also, 29.5% of the QoL variability is explained by creativity. A cluster analysis sorted out three different groups: very creative persons (VCP); mildly creative persons (MCP); slightly creative persons (SCP). VCPs have a significantly lower level of depression and have a better QoL compared to SCPs. MCPs have a level of depression between the other groups and a similar level of QoL than VCPs. These results suggest that creativity could have a noticeable influence on how patients experience their cancer. Further studies on this phenomenon will be necessary for creativity to be taken into account for psychological follow-up in oncology.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Impact of immune checkpoint inhibitor (CPI) and EGFR tyrosine kinase inhibitor (TKI) sequence on time to treatment failure (TTF) among EGFR plus NSCLC treated in a community-based cancer research network.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9099-9099
Author(s):  
Carissa Jones ◽  
Rebecca Lachs ◽  
Emma Sturgill ◽  
Amanda Misch ◽  
Caressa Lietman ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Survival Rates ◽  
Research Network ◽  
Sample Sizes ◽  
Loss To Follow Up ◽  
Kaplan Meier ◽  
Oncogenic Driver ◽  
The Impact

9099 Background: The development of CPIs and driver-targeted TKIs has transformed the treatment of NSCLC and increased survival rates. However, the role of CPIs in patients with oncogenic-driven NSCLC remains an area of investigation. We sought to examine the impact of CPI sequence on treatment response among patients with oncogenic-driver mutation-positive NSCLC. Methods: Patients with NSCLC being treated within the Sarah Cannon Research Institute network were identified through Genospace, Sarah Cannon’s clinico-genomic analytics platform. Advanced stage oncogenic-driven tumors (driver+) were defined as those with a record of receiving an FDA-approved TKI targeting EGFR, ALK, RET, ROS1, NTRK, MET, or BRAF. Kaplan-Meier estimates were used to examine TTF (defined as time from therapy start to start of next therapy, death, or loss to follow-up) and overall survival (OS). Results: We identified 12,352 patients with lung cancer and available therapy data (2005-2020), including 2,270 (18%) driver+ patients. Eleven percent (N=245) of driver+ patients received a CPI, including 120 (49%) with CPI prior to TKI, 122 (50%) with CPI post TKI, and 3 (1%) who received CPI both pre and post TKI. The CPI TTF was significantly longer for those who received CPI post TKI compared to those who received it prior (Table). EGFR+ tumors accounted for 82% (N=1,867) of driver+ patients, 10% of whom (N=188) received a CPI. Of the EGFR+/CPI+ patients, 78 patients (41%) received CPI prior to TKI, 107 (57%) received CPI post TKI, and 3 (2%) received CPI both pre and post TKI. EGFR+ tumors exposed to a CPI post TKI had a longer CPI TTF compared to patients who received it prior (Table). In contrast, there was no difference in length of benefit from TKI if it was received pre vs. post CPI (Table). There was also no difference in OS based on sequence of TKI and CPI (p=0.88). Larger sample sizes are needed for analysis of additional driver-stratified cohorts. Conclusions: Patients with oncogenic-driven NSCLC benefited from CPI longer when it was administered after TKI compared to before. Importantly, therapy sequence only affected length of benefit from CPIs and did not affect length of benefit from TKIs. This effect was present in EGFR+ NSCLC, but sample sizes were too small to determine if the same is true for other oncogenic-drivers. Therapy sequence had no impact on OS, indicating the presence of additional clinical, therapeutic, and/or genomic factors contributing to disease progression. Continued research is needed to better understand markers of CPI response in driver+ NSCLC.[Table: see text]

Outcomes of stereotactic radiosurgery for pilocytic astrocytoma: an international multiinstitutional study

2021 ◽  
Vol 134 (1) ◽  
pp. 162-170 ◽  
Author(s):  
Erin S. Murphy ◽  
Shireen Parsai ◽  
Hideyuki Kano ◽  
Jason P. Sheehan ◽  
Roberto Martinez-Alvarez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stereotactic Radiosurgery ◽  
Pilocytic Astrocytoma ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Gamma Knife Radiosurgery ◽  
Initial Therapy ◽  
Single Session ◽  
Current Standard

OBJECTIVEThe current standard initial therapy for pilocytic astrocytoma is maximal safe resection. Radiation therapy is considered for residual, recurrent, or unresectable pilocytic astrocytomas. However, the optimal radiation strategy has not yet been established. Here, the authors describe the outcomes of stereotactic radiosurgery (SRS) for pilocytic astrocytoma in a large multiinstitutional cohort.METHODSAn institutional review board–approved multiinstitutional database of patients treated with Gamma Knife radiosurgery (GKRS) between 1990 and 2016 was queried. Data were gathered from 9 participating International Radiosurgery Research Foundation (IRRF) centers. Patients with a histological diagnosis of pilocytic astrocytoma treated using a single session of GKRS and with at least 6 months of follow-up were included in the analysis.RESULTSA total of 141 patients were analyzed in the study. The median patient age was 14 years (range 2–84 years) at the time of GKRS. The median follow-up was 67.3 months. Thirty-nine percent of patients underwent SRS as the initial therapy, whereas 61% underwent SRS as salvage treatment. The median tumor volume was 3.45 cm3. The tumor location was the brainstem in 30% of cases, with a nonbrainstem location in the remainder. Five- and 10-year overall survival rates at the last follow-up were 95.7% and 92.5%, respectively. Five- and 10-year progression-free survival (PFS) rates were 74.0% and 69.7%, respectively. On univariate analysis, an age < 18 years, tumor volumes < 4.5 cm3, and no prior radiotherapy or chemotherapy were identified as positive prognostic factors for improved PFS. On multivariate analysis, only prior radiotherapy was significant for worse PFS.CONCLUSIONSThis represents the largest study of single-session GKRS for pilocytic astrocytoma to date. Favorable long-term PFS and overall survival were observed with GKRS. Further prospective studies should be performed to evaluate appropriate radiosurgery dosing, timing, and sequencing of treatment along with their impact on toxicity and the quality of life of patients with pilocytic astrocytoma.

Salvage Autologous Hematpoeitic Stem Cell Transplants (AHSCT2) for Myeloma: Single Center Experience.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4591-4591
Author(s):  
Bishoy Faltas ◽  
Jane L. Liesveld ◽  
Michael Becker ◽  
Jainulabdeen J. Ifthikharuddin ◽  
Gordon L. Phillips
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Median Overall Survival ◽  
Progressive Disease ◽  
Conflicts Of Interest ◽  
High Dose ◽  
The Impact

Abstract Abstract 4591 Although the role of AHSCT1 is well established in multiple myeloma therapy, the role of the salvage (not “tandem”) AHSCT2 is less clear. However, most pts. undergo initial stem cell harvests with plans for eventual AHSCT2. To clarify the indications, the prognostic factors and the outcomes of AHSCT2 in relapsed myeloma, we analyzed our experience in 19 pts. (pts.) who underwent salvage AHSCT2 between the 1994–2008. Mean age at AHSCT1/2 was 54.58 (SD 7.96)/57.03 (SD 8.10) respectively; 15 (79.0%) were males. At the time of diagnosis, 7 (36.8%) pts. had ISS stage I, 6 (31.6%) stage II, 3(15.8%) stage III and in 3 (15.8%) the ISS stage could not be determined. Isotypes: IgG 11 (57.9%), IgA 4 (21.1%), 1 (5.3%) pt. had IgM and 3 (15.8%) had light chain myeloma. Cytogenetics were normal in 6 (31.6%), abnormal in 5 (26.3%) and unavailable for 8 (42.1%) pts. The most common therapy received prior to AHSCT1 was Vincristine/Adriamycin/Dexamethasone in 11 (57.9%) pts.; 7 pts. were exposed to novel agents. One pt. achieved complete response (CR), 15 (79.0%) pts. achieved partial response (PR) and 3 (15.8%) pts. had stable or progressive disease after receiving the initial treatment. All pts. proceeded to receive high dose therapy with Melphalan (MEL), 2 pts received fTBI in addition to MEL. Mean MEL dose was 190.00 mg/m2 (SD 23.01); 15 pts. received 200 mg/m2. All pts. received >2×10e6/kg of CD34+ cells in the first and second transplants. At D+100 after AHSCT1, responses were: 4 (21.1%) CR, 1 (5.3%) VGPR, 8 (42.1%) PR and 6 (31.6 %) with lesser responses. Therapy to prolong response or for salvage after AHSCT1 was given in all pts before AHSCT2, including Thalidomide in 6 (31.6%), Bortezomib in 4 (21.1%) and Lenalidomide in 2 (10.5) pts. Median time to progression after AHSCT1 was 318 days [95 % CI 110– 573]. Median interval between AHSCT1 and AHSCT2 was 896.74 days (SD: 698.34 days). At the time of AHSCT2, 4 (21.1%) were in PR, 15 (79.0%) had progressive disease. For AHSCT2, all pts. Received MEL, one pt. received MEL + Cytoxan and one pt. received MEL + Bortezomib. The median MEL dose/m2 was 175.56 (52.04).All pts. survived AHSCT2 to D+100, responses were as follows: 3 (15.8%) VGPR, 9 (47.4%) in PR; 7 (36.9) pts. had lesser responses. After AHSCT2, nine (47.4%) pts. had grade III toxicity and only one pt. had grade IV toxicity (avascular necrosis). Maintenance therapy after AHSCT2 included Bortezomib in 7 (36.8%) pts., Lenalidomide in 5 (26.3%) pts. and Thalidomide in 4 (21.1%) pts. After AHSCT2, the median overall survival (OS) was 658 days [95 % CI 326–1330] and progression free survival (PFS) after AHSCT2 was 237 days [95 % CI 121– 397] (Figure 1). OS probability at 6, 12, 24 months after AHSCT2 was 81.3, 75.0, 39.3 % respectively. For all pts., the median OS time (i.e. time from diagnosis to death or last follow-up) was 2187 days [95% CI 1413– 4126]. At the end of the follow up period, a total of 14 pts. had died. Causes of death were progression in 12 (63.2%) and sepsis in 2 pts. (10.5%). The number of previous lines of chemotherapy, interval between transplants, disease status at the time of AHSCT1/2, type of myeloma and MEL dose were not predictive of OS and PFS. In the multivariate analysis, only age by decade at AHSCT2 and male gender were independent predictors of OS after AHSCT2 (HR 4.037, P= 0.01), (HR 3.74, P=0.07) respectively. Similarly, in the multivariate analysis for PFS after AHSCT2, age at AHSCT2 was an unfavorable independent predictor (HR 3.48, P=0.009) whereas relapse free response more than 18 months after AHSCT1 was an independent favorable predictor (HR 0.198, P=0.007).Our results are consistent with the few studies examining the impact of salvage transplants for myeloma which report a median overall survival ranging from 20.7 to 38.1 months from the time of AHSCT2.We conclude that salvage AHSCT2 can positively impact PFS and OS but efforts to improve outcomes are mandatory.FigureSEQ Figure ≂,* ARABIC 1Figure. SEQ Figure ≂,* ARABIC 1 X-axis represents time from AHSCT2 in days. Y axis represents survival distribution. Blue line = OS, Red = PFS. Disclosures: No relevant conflicts of interest to declare.

What Is the Frequency of Transplant-Eligible Multiple Myeloma Patients Being Cured? the Impact of an MGUS-like Signature at Diagnosis and MRD-Negativity

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 725-725 ◽  
Author(s):  
Bruno Paiva ◽  
Maria Belen Vidriales ◽  
Noemi Puig ◽  
Teresa Cedena ◽  
Lourdes Cordon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Binding Site ◽  
Residual Disease ◽  
Limit Of Detection ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Classification Model ◽  
The Impact

Abstract Introduction: Although multiple myeloma (MM) is typically described as an incurable disease, it has been shown in recent years that a small fraction of patients may reach more than 10-years progression-free survival (PFS), which is considered as the minimum threshold to identify patients in "operational cure". However, because of the scarcity of available data there is significant lack of knowledge in MM regarding the frequency of cases attaining operational cure, nor the existence of biomarkers that could prospectively predict such curability. Methods: Herein, we sought to define the frequency as well as the biomarkers predictive of operational cure in a large series of uniformly-treated transplant-eligible patients enrolled in the PETHEMA/GEM2000 protocol (VBMCP/VBAD followed by HDT/ASCT and 2 years of maintenance with interferon and prednisone). Patients' follow-up was updated at the time of abstract submission, and the median follow-up of the series is now of 12-years. We used an automated multiparameter flow cytometric (MFC) classification model focused on the analysis of the bone marrow plasma-cell compartment to identify among newly diagnosed symptomatic MM those with MGUS-like vs. MM-like phenotypic signatures. Minimal residual disease (MRD) was monitored using a first-generation 4-color MFC assay (CD38-FITC / CD56-PE / CD19-PerCPCy5.5 / CD45-APC) with a limit of detection of 10-4. PFS and overall survival (OS) were measured from the time of diagnosis. Results: From a total of 1075 patients enrolled in the GEM2000 protocol, 763 were eligible for this analysis because they either relapsed or died during the first 10-years from diagnosis (n=666; 87%), or remained progression-free and alive for more than 10-yers (n=97; 13%); accordingly, all patients remaining progression-free and alive but for which the follow-up was inferior to 10-years were excluded from the analysis. We then investigated the biomarkers that could help to identify patients reaching operational cure after HDT/ASCT. As compared to the vast majority of cases, patients reaching >10-years PFS (13%) had significantly less frequent anemia (76% vs. 60%, respectively; P=.002), as well as more frequent Durie-Salmon stage IA (14% vs. 6%; P=.004), MGUS-like signature as determined by the automated MFC algorithm (28% vs. 6%; P<.001), complete response (CR) after HDT/ASCT (51% vs. 35%; P=.003), and MRD-negativity by MFC (72% vs. 31%; P<.001). Other biomarkers such as ISS, LDH, ploidy and proliferation were not significantly different among patients reaching >10-years PFS vs. those who relapsed earlier. On multivariate analysis, only the presence of an MGUS-like signature at baseline (P=.04; HR: 3.9) and MRD-negativity at day+100 after HDT/ASCT (P=.006; HR: 6.3) emerged as independent predictive markers for >10-years PFS; anemia, Durie-Salmon and CR status were not retained in the logistic regression model. Accordingly, patients with an MFC-defined baseline MGUS-like signature reaching MRD-negativity after HDT/ASCT (n=14) had a median PFS of 10-years and a 10-year OS rate of 79%, which were significantly superior to those observed among cases with MM-like signatures being MRD-negative (n=54) or positive (n=99) after therapy [median PFS of 6 and 3 years (P<.001); 10-year overall survival rates of 55% and 19% (P<.001)]. Conclusions: We demonstrated that operational cure (i.e.: >10-years PFS) was possible for 13% of transplant-eligible MM patients before the era of novel agents. Curability rates were particularly frequent among patients with a benign phenotypic signature at diagnosis and MRD negativity after HDT/ASCT, suggesting a remarkable clinical benefit of attaining deep remissions after intensive treatment for patients with early MM. Disclosures Paiva: Sanofi: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Onyx: Consultancy; BD Bioscience: Consultancy; EngMab AG: Research Funding; Binding Site: Consultancy; Celgene: Consultancy. Puig:The Binding Site: Consultancy; Janssen: Consultancy. Mateos:Takeda: Consultancy; Celgene: Consultancy, Honoraria; Onyx: Consultancy; Janssen-Cilag: Consultancy, Honoraria. San Miguel:Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Onyx: Honoraria; Sanofi-Aventis: Honoraria; Novartis: Honoraria; Millennium: Honoraria; Janssen-Cilag: Honoraria.

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