Prognostic Significance of Tumor Response at the End of Therapy in Group III Rhabdomyosarcoma: A Report From the Children's Oncology Group

Purpose Some patients with rhabdomyosarcoma (RMS) achieve less than a complete response (CR) despite receiving all planned therapy. We assessed the impact of best response at the completion of all therapy on patient outcome. Patients and Methods We studied 419 clinical group III participants who completed all protocol therapy without developing progressive disease for Intergroup Rhabdomyosarcoma Study (IRS) IV. Response (complete resolution [CR], partial response [PR; ≥ 50% decrease], or no response [NR; < 50% decrease and < 25% increase]) was determined by radiographic measurement and categorized by the best response. Results At the end of therapy, 341 participants (81%) achieved a best response of CR and 78 (19%) had a best response of PR/NR. Five-year failure-free survival was similar for participants achieving CR (80%) and PR/NR (78%). After adjustment for age, nodal status, primary site, and histology, there was no significant indication of lower risk of failure (hazard ratio [HR], 0.77; 95% CI, 0.46 to 1.27; P = .3) nor death (HR, 0.63; 95% CI, 0.36 to 1.09; P = .1) for CR versus PR/NR participants. Seventeen participants with a best response of PR/NR had surgical procedures; eight (50%) of 16 with available pathology reports had residual viable tumor and only three achieved a complete resection. Resection of residual masses was not associated with improved outcome. Conclusion CR status at the end of protocol therapy in clinical group III participants was not associated with a reduction of disease recurrence and death. Aggressive alternative therapy may not be warranted for RMS patients with a residual mass at the end of planned therapy.

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Achievement of Complete Response Is a Strong Prognostic Factor In Elderly Newly Diagnosed Myeloma: Retrospective Analysis of 1175 Patients

Blood ◽

10.1182/blood.v116.21.1949.1949 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1949-1949

Author(s):

Francesca Gay ◽

Alessandra Larocca ◽

P.W. Wijermans ◽

Sara Bringhen ◽

Tommasina Guglielmelli ◽

...

Keyword(s):

Board Of Directors ◽

Complete Response ◽

New Drugs ◽

Response To Treatment ◽

Maximal Response ◽

High Dose ◽

Newly Diagnosed ◽

Advisory Committees ◽

Best Response ◽

The Impact

Abstract Abstract 1949 Introduction: There is extensive evidence from numerous studies in the transplant setting that achievement of complete response (CR) or at least very good partial response (VGPR) is significantly associated with prolonged progression-free survival (PFS) and overall survival (OS). In elderly myeloma patients CR was a rare event since new drugs has been added to standard melphalan-prednisone (MP). After the introduction of novel agents, CR represents an achievable goal, also outside of the transplant setting. Aims: to assess the impact of response to treatment on time-to-event parameters (PFS and OS) in elderly myeloma patients. Methods: We retrospectively analysed newly diagnosed myeloma patients, older than 65 years old, or younger but not eligible for high-dose chemotherapy and transplant. Patients were enrolled in 3 multicentre randomized European trials of the GIMEMA and Hovon groups, and were treated with MP (n=332), MP plus thalidomide (MPT, n=332), MP plus bortezomib (VMP, n=257) or MP plus bortezomib-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT, n=254). PFS, OS and duration of CR were analysed by the Cox proportional hazards model, comparing the two arms by the Wald test and calculating 95% confidence interval (CI). Univariate and multivariate analyses were performed for the following variables: age at diagnosis (>75 vs. ≤75 yrs), International Staging System (ISS) stages, type of chemotherapy and best response achieved. Best response was treated as a time-dependent variable. Results: A total of 1,175 patients, enrolled from November, 2001 to January, 2009, were retrospectively analysed. The best response to treatment was available in 1,136 patients: CR was reported in 195, VGPR in 212, PR in 397. Baseline characteristics according to best response achieved in patients who obtained CR, VGPR or PR were similar. Since response rates vary according to treatment regimens the proportion of patients who received MP, MPT, VMP, and VMPT-VT was different in the different response categories. After a median follow-up of 29 months, PFS was significantly higher in patients who achieved CR compared to those who obtained VGPR (HR 0.16; 95% CI 0.10–0.24; p<0.001) or PR (HR 0.07; 95% CI 0.04–0.13; p<0.001). The advantage in PFS translated into an advantage in OS: patients obtaining CR have a significantly prolonged OS than patients who achieved VGPR (HR 0.15; 95% CI 0.08–0.28; p<0.001) or PR (HR 0.08; 95% CI 0.04–0.16, p<0.001), (table). In multivariate analysis CR achievement was as an independent predictor of longer PFS and OS, regardless of age, ISS stage, and treatment administered. In patients > 75 years, both PFS and OS were shorter as compared to younger patients. Despite these differences, the impact of CR on outcome was identical. In the subgroup of patients > 75 years, PFS was significantly prolonged in patients who achieved CR, compared with those who obtained VGPR (HR 0.26; 95% CI 0.12–0.58, p = 0.001) or PR (HR 0.20; 95% CI 0.10–0.41, p < 0.001). Accordingly, OS was significantly higher in patients who achieved CR, compared with those who obtained VGPR (HR 0.13; 95% IC 0.03–0.58; p = 0.007), or PR (HR 0.12; 95% IC 0.03–0.51, p = 0.004), (table). No significant PFS differences between patients obtaining CR during the first 6 months of treatment or later were seen (HR 1.06; 95% IC 0.49–2.27; p=0.878). Similarly, no OS differences between these two groups were detected (p = 0.676). Duration of CR was comparable in patients who obtained CR during or after the first 6 months of treatment (HR 0.66; 95% CI 0.30–1.45; p = 0.305). Patients whose CR lasted more than 18 months have a significant OS benefit compared to patients who did not (p=0.006). Conclusions: These finding highlight the importance of CR, also outside of the transplant setting, regardless of age, ISS and treatment administered, and support the use of new drugs, also in patients older than 75 years, to achieve and maintain maximal response. Disclosures: Gay: Celgene: Honoraria. Bringhen:Calgene: Honoraria; Janssen-Cilag: Honoraria. Guglielmelli:Celgene: Honoraria; Janssen Cilag: Honoraria. Boccadoro:Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees. Sonneveld:Celgene: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson : Membership on an entity's Board of Directors or advisory committees. Palumbo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Evaluation of early response by anatomic imaging to predict survival among patients with group III rhabdomyosarcoma: A report from the Children’s Oncology Group.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.10012 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 10012-10012

Author(s):

Douglas S. Hawkins ◽

Abby R. Rosenberg ◽

Elizabeth Lyden ◽

James Robert Anderson ◽

David A. Rodeberg ◽

...

Keyword(s):

Clinical Trial ◽

Objective Response ◽

Prognostic Significance ◽

Complete Response ◽

Early Response ◽

Response To Therapy ◽

Rank Test ◽

Oncology Group ◽

Group Iii ◽

Kaplan Meier

10012 Background: The prognostic significance of response to induction therapy for rhabdomyosarcoma (RMS) by anatomic imaging (computerized tomographic [CT] or magnetic resonance imaging [MRI] scan) is controversial. We previously reported no relationship between early response and failure-free survival (FFS) for patients on IRS-IV. We repeated the same analysis using an independent cohort of patients with non-metastatic, initially unresected RMS treated on a more recent clinical trial. Methods: A total of 338 patients enrolled in Children’s Oncology Group study D9803 met the following inclusion criteria for this analysis: 1) non-metastatic, initially unresected (Group III); 2) embryonal (ERMS) or alveolar (ARMS) histology; 3) documented response to induction chemotherapy (excluding progressive disease) based on anatomic imaging; and 4) documented therapy beyond week 12. Response at week 12 was determined by the treating institution as complete response (CR, complete resolution), partial response (PR, decrease of >= 50% of the sum of the products of maximum perpendicular diameters), or no response (NR, between 50% reduction and 25% increase in the sum of the products of maximum perpendicular diameters). FFS was estimated using the Kaplan-Meier method, and comparisons between groups were made using the log-rank test. Results: Overall objective response rate (CR+PR) at week 12 of therapy was 85%, with similar responses for ERMS and ARMS. FFS was similar among all patients with CR, PR, or NR (p=0.49). Restricting the analysis to either ERMS or ARMS, there was no difference in FFS by histology (p=0.20 and p=0.45, respectively). Conclusions: These findings provide additional evidence that anatomic imaging assessment of early response to therapy among RMS patients does not predict outcome and should not be used to tailor subsequent therapy. Clinical trial information: NCT00003958. [Table: see text]

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The impact of prostate cancer (PC) margin extent (ME) at radical prostatectomy (RP) on biochemical relapse-free survival (bRFS).

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.83 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 83-83

Author(s):

Steven Neema Seyedin ◽

Sarah L Mott ◽

Anthony N Snow ◽

James Kyle Russo ◽

John Watkins

Keyword(s):

Risk Stratification ◽

Multivariable Analysis ◽

Surgical Margin ◽

Recurrence Risk ◽

Disease Recurrence ◽

Accurate Estimation ◽

Clinicopathologic Factor ◽

Pathology Reports ◽

The Impact

83 Background: Surgical margin involvement (M+) by PC at RP is associated with suboptimal bRFS; however, the interaction of M+ with coincident high-risk clinicopathologic and treatment factors obscures accurate estimation of recurrence risk. The objective of this study is to determine whether ME permits risk stratification. Methods: Retrospective analysis of clinicopathologic factor association with bRFS. Eligible patients underwent RP alone for clinically localized PC. Patients with metastatic disease, PSA > 30 at diagnosis, pathologic involvement of seminal vesicles or lymph nodes at RP, insufficient follow-up, or receipt of pre-RP or adjuvant therapy were excluded. Slides from RP specimens with close or positive margins were re-reviewed by study pathologists blinded to outcome. Results: From 2002-2010, 667 patients were eligible for analysis. The median age was 61 yrs (range, 43-76), and all had cT1-2 disease (83% T1c), with median PSA 5.6 (0.9-28.0; 85% ≤10). Robot-assisted RP was employed in 141 cases (21%). Two hundred ten patients (31%) had M+, with single maximal ME 3mm (0.1-23), and cumulative ME 4mm (0.1-34). At median follow-up of 102 months (13-184), 149 patients (22%) had recurrence, with estimated 8-year bRFS rates of 85%/56% for M-/+ patients (p < 0.01). Multivariable analysis identified PSA, Gleason score (GS), extraprostatic extension, and M+ as associated with bRFS. Specific to patients with involved margins, the combination of ME and GS permitted recurrence risk stratification, with a low-risk subset identified (GS≤6 and ME < 3mm; Table). Conclusions: The current investigation suggests that GS6 patients with maximal or cumulative ME < 3mm appear to have favorable early 8-year bRFS following RP. GS6 patients with wider ME and GS ≥7 with any extent M+ appear to have suboptimal bRFS. RP pathology reports should include ME details, in order to more precisely estimate risk of subsequent disease recurrence. [Table: see text]

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Importance of Achieving a Complete Response in Multiple Myeloma, and the Impact of Novel Agents

Journal of Clinical Oncology ◽

10.1200/jco.2009.25.4250 ◽

2010 ◽

Vol 28 (15) ◽

pp. 2612-2624 ◽

Cited By ~ 153

Author(s):

Asher A. Chanan-Khan ◽

Sergio Giralt

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Prognostic Significance ◽

Complete Response ◽

Maximal Response ◽

Prognostic Impact ◽

Long Term Outcomes ◽

First Line ◽

The Impact

The goal of treatment for multiple myeloma (MM) is to improve patients' long-term outcomes. One important factor that has been associated with prolonged progression-free and overall survival is the quality of response to treatment, particularly achievement of a complete response (CR). There is extensive evidence from clinical studies in the transplant setting in first-line MM demonstrating that CR or maximal response post-transplant is significantly associated with prolonged progression-free and overall survival, with some studies demonstrating a similar association with postinduction response. Supportive evidence is also available from studies in the nontransplant and relapsed settings. With the introduction of bortezomib, thalidomide, and lenalidomide, higher rates of CR are being achieved in both first-line and relapsed MM compared with previous chemotherapeutic approaches, thereby potentially improving long-term outcomes. While standard CR by established response criteria has been shown to have differential prognostic impact compared with lesser responses, increasingly sensitive analytic techniques are now being explored to define more stringent degrees of CR or elimination of minimal residual disease (MRD), including multiparameter flow cytometry and polymerase chain reaction. Demonstrating eradication of MRD by these techniques has already been shown to predict for improved outcomes. Here, we review the prognostic significance of achieving CR in MM and highlight the importance of CR as an increasingly realizable goal at all stages of treatment. We discuss clinical management issues and provide recommendations relevant to practicing oncologists, such as the routine use of sensitive techniques for assessment of disease status to inform evidence-based decisions on optimal patient management.

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Study of the Outcome of Pediatric Patients with Aplastic Anemia treated with Immunosuppressive Therapy at Ain Shams University Pediatric Hospital

QJM ◽

10.1093/qjmed/hcab113.052 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

W Mohamed ◽

S Matboly ◽

N Morcy

Keyword(s):

Aplastic Anemia ◽

Immunosuppressive Therapy ◽

Alternative Therapy ◽

Patient Characteristics ◽

Complete Response ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Pediatric Age Group ◽

Best Response ◽

Life Threatening

Abstract Background Aplastic anemia (AA) is life threatening disorder in pediatric age group with an increasing incidence nowadays. Hematopoietic stem cell transplant being the 1st line therapy; immunosuppressive therapy (IST) is the alternative therapy and is the most commonly used modality of treatment especially in the developing countries. Aim of the Work to assess the outcome of IST in children with severe and very severe AA. Patients and Methods Data for 23 children treated with IST from January 201 0 to January 201 9 (10 years) were retrieved from clinic records. IST included rabbit anti thymocyte globulin (ATG) along with cyclosporine A and another group were treated by sandimmune alone. Results Patient characteristics included median age (9) with 73.9% male and 26.1% female. With median interval between diagnosis and start of IST 2(1 -5) months and around 30.4% with hepatitis A associated aplastic anemia. Complete response, and no response were seen in 4 (50%) patients and 4(50%) patients, respectively in patients received ATG and sandimune. While in patients received sandimune alone complete response, partial response and no response were seen in 7(46.7%) patients, 5 (33.3%) patients, and 3 (20%) patients respectively. The median time to best response in the whole cohort was 2 months. There was no difference in outcome related to severity of AA, or higher Hb or platelet level. There was a significantly better rate of response in both groups of patients with higher initial TLC count (p = 0.001) initial ANC (p = 0.002), initial ALC (p = 0.001), and initial ARC (p = 0.014) before start of IST. An overall response rate in both groups around of 43.47% reported a 5-year OS. With 45.5 of patients with complete response had HAAA. A delayed time to complete response with prolonged requirement of cyclosporine therapy was detected in the study. Conclusion In a developing country setting, IST with ATG and cyclosporine seems to be an alternative treatment for children with aplastic anemia lacking MRD.

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The impact of sequencing PD-1/PD-L1 inhibitors and stereotactic radiosurgery for patients with brain metastasis

Neuro-Oncology ◽

10.1093/neuonc/noz046 ◽

2019 ◽

Vol 21 (8) ◽

pp. 1060-1068 ◽

Cited By ~ 18

Author(s):

Rupesh Kotecha ◽

Joseph M Kim ◽

Jacob A Miller ◽

Aditya Juloori ◽

Samuel T Chao ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Checkpoint Inhibitors ◽

Combined Modality Therapy ◽

Objective Response ◽

Complete Response ◽

Substantial Effect ◽

Durable Response ◽

Best Response ◽

Programmed Cell Death 1 ◽

The Impact

Abstract Background The response of brain metastases (BM) treated with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs; programmed cell death 1 and its ligand) is of significant interest. Methods Patients were divided into cohorts based on ICI sequencing around SRS. The primary outcome was best objective response (BOR) that was lesion specific. Secondary outcomes included overall objective response (OOR), response durability, radiation necrosis (RN), and overall survival (OS). Results One hundred fifty patients underwent SRS to 1003 BM and received ICI. Five hundred sixty-four lesions (56%) treated with concurrent ICI (±5 half-lives) demonstrated superior BOR, OOR, and response durability compared with lesions treated with SRS and delayed ICI. Responses were best in those treated with immediate (±1 half-life) ICI (BOR: −100 vs −57%, P < 0.001; complete response: 50 vs 32%; 12-month durable response: 94 vs 71%, P < 0.001). Lesions pre-exposed to ICI and treated with SRS had poorer BOR (−45%) compared with ICI naive lesions (−63%, P < 0.001); best response was observed in ICI naive lesions receiving SRS and immediate ICI (−100%, P < 0.001). The 12-month cumulative incidence of RN with immediate ICI was 3.2% (95% CI: 1.3–5.0%). First radiographic follow-up and best intracranial response were significantly associated with longer OS; steroids were associated with inferior response rates and poorer OS (median 10 vs 25 mo, P = 0.002). Conclusions Sequencing of ICI around SRS is associated with overall response, best response, and response durability, with the most substantial effect in ICI naive BM undergoing immediate combined modality therapy. First intracranial response for patients treated with immediate ICI and SRS may be prognostic for OS, whereas steroids are detrimental.

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Prognostic value of stringent complete response (sCR) post-autologous stem cell transplant (SCT) in multiple myeloma (MM)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.8587 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 8587-8587

Author(s):

P. Kapoor ◽

S. Kumar ◽

A. Dispenzieri ◽

M. Q. Lacy ◽

S. R. Hayman ◽

...

Keyword(s):

Plasma Cells ◽

Response Duration ◽

Complete Response ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Entire Cohort ◽

Best Response ◽

Prognostic Utility ◽

Response State ◽

The Impact

8587 Background: The measurement of serum immunoglobulin free light chains (FLC) has diagnostic and prognostic utility in MM. Normalization of the FLC ratio may define a deeper complete response after therapy than by standard criteria of CR. A sCR requires normalization of the FLC ratio and absence of clonal plasma cells in the bone marrow (BM) in addition to the standard criteria for CR. The objective of our study was to evaluate the impact of specific types of CR [sCR, CR or near CR (nCR/ immunofixation positive CR)] post-SCT on time to progression (TTP) and overall survival (OS). Methods: 468 MM patients who had achieved at least a partial response post-SCT were studied. The results of serum and urine protein studies, serum FLC assay, and BM evaluation, including measurement of marrow plasma cell clonality by immunohistochemistry obtained ≥60 days after SCT were used to determine the best response. TTP was defined as the time from SCT to progression, with non-myeloma related deaths censored. Results: 179 patients achieved varying degrees of CR as their best response. 39, 35 and 105 patients achieved nCR, CR and sCR, respectively. The median estimated follow-up for the entire cohort was 52 months from the diagnosis and 41 months from SCT. The median TTP was 15, 29 and 35 months for patients achieving nCR, CR and sCR, respectively (P<0.0001). The median OS for patients achieving nCR was 53 months from the diagnosis, but not reached for those with a CR or sCR (P=0.0009). The 5-year OS was 80% and 79% for patients with CR and sCR, respectively (P=NS). Similarly, OS from SCT was significantly shorter in patients achieving nCR (42 months vs. not reached for patients in CR and sCR; P<0.001). Conclusions: Achievement of a sCR represents a deeper response state compared to conventional CR, translating to a longer response duration post SCT, validating its inclusion in the modified uniform response criteria. While we did not see a significant improvement in OS with sCR compared to CR in this group, this question needs to be addressed in a larger study. The step wise improvement in the response duration across nCR, CR and sCR highlights the contribution of immunofixation studies, marrow assessment of clonality and FLC estimates. [Table: see text]

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Achievement of Complete Response Is Important for Longer Overall Survival in Patients with Newly Diagnosed Myeloma: A Single-Institutional Study

Blood ◽

10.1182/blood.v118.21.5115.5115 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5115-5115

Author(s):

Kanichi Iwama ◽

Tomotaka Ugai ◽

Hiroki Sugihara ◽

Masayuki Yamakura ◽

Masami Takeuchi ◽

...

Keyword(s):

Overall Survival ◽

Partial Response ◽

Complete Response ◽

Novel Agents ◽

Response To Treatment ◽

Prognostic Impact ◽

Female Ratio ◽

Best Response ◽

The Impact

Abstract Abstract 5115 INTRODUCTION. Even with the introduction of novel therapeutic agents, including thalidomide, bortezomib, and lenalidomide, multiple myeloma (MM) is an incurable disease. Deeper responses, such as complete response (CR) and very good partial response (VGPR), are major goals of treatment to obtain long-term overall response (OS) and progression-free response (PSF) in patients with MM. Recent large randomized retrospective studies also suggested improved OS and PFS in patients who achieved deeper responses. However, the prognostic impact of achieving CR or VGPR remains controversial. In addition, these studies included selected patients that may not be representative of the general population. Therefore, we analyzed cases in our database to evaluate the impact of treatment response on the outcome of consecutive patients with symptomatic MM who were treated with chemotherapeutic regimens containing novel agents over the past 6 years at our institution in Kamogawa City, Japan. PATIENTS AND METHODS. We included 97 consecutive patients treated at our institution between April 2005 and May 2011. The study population consisted of 56 male and 41 female patients with a median age of 70 years old (range: 45 −90). Due to the rapid changes in treatment modality and government approval of novel agents in myeloma during this period, initial treatment could not be uniformly categorized, but all patients received chemotherapy regimens containing at least one novel agent, including thalidomide, bortezomib, and lenalidomide. These patients were thought to be more representative of the general myeloma population. Seventy-seven (79.4%), 27 (38.6%), and 55 (56.7%) patients received bortezomib-, lenalidomide-, and thalidomide-containing regimens, respectively. Treatment responses were assessed using the International Myeloma Working Group (IMWG) criteria with minor modifications, and the best response to treatment during the course of disease was evaluated. Immunofixation test and serum free light chain measurements were performed for confirmation of CR and stringent CR. OS was calculated from the time of diagnosis until the date of death from any cause or the date on which the patient was last known to be alive. Univariate and multivariate analyses were performed for the following variables: age at diagnosis, International Staging System (ISS), and best response achieved. RESULT. The median age of patients was 71 y.o. (range: 49 −90 y.o.), and the male to female ratio was 56:41. The best responses to treatment were as follows: CR was obtained in 19 cases (19.6%), VGPR in 29 (29.9%), partial response (PR) in 34 (35.0%), and stable disease (SD) or less in 15 (15.4%). Baseline characteristics according to best response achieved in patients who achieved CR, VGPR, PR, and SD or less were similar among the patients ≥70 y.o. vs. ≤70 y.o. Patients' age has no impact on the response to treatment. With a median follow-up of 25 months, Kaplan–Meier estimated 3-year and 5-year overall survival (OS) rates were 67.2% and 35.0%, respectively. The 3- and 5-year OS were 100% in patients with CR, which were significantly superior in patients with VGPR (3-y 70%, 5-y 55.0%) and PR (3-y 60%, 5-y 23.0%). The 3- and 5-year OS were not significantly different between patients with VGPR and PR. Normalization of FLC kappa/Lambda ratio was observed in 15 of 19 (80%) patients with CR, 15 of 29 (51%) with VGPR, 4 of 34 (6.6%) in PR, and in none of 15 (0%) in SD or less. Patients who showed normalization of FLC kappa/Lambda ratio had significant OS benefit compared to those who did not. Proportional hazard Cox models showed that patients with ISS stage I/II had better 5-year OS rate compared to patients with stage III (51%; 20%, P = 0.005). However, there was no association between ISS stage and achievement of CR. CONCLUSION. The results of the present study highlighted the importance of achieving CR, not PR or VGPR, and normalization of FLC kappa/Lambda ratio for obtaining long-term OS in patients with MM regardless of age or ISS stage. Disclosures: No relevant conflicts of interest to declare.

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The components of progression as explanatory variables for overall survival in the RECIST database.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10602 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 10602-10602

Author(s):

Saskia Litière ◽

Elisabeth De Vries ◽

Lesley Seymour ◽

Daniel J. Sargent ◽

Lalitha Shankar ◽

...

Keyword(s):

Overall Survival ◽

Randomized Clinical Trials ◽

Cox Regression ◽

Complete Response ◽

Tumor Type ◽

Explanatory Variables ◽

Best Response ◽

Rate Of Increase ◽

Target Disease ◽

The Impact

10602 Background: Progressive disease (PD) according to RECIST 1.1 (Eisenhauer et al, 2009) is defined as one or more of (1) PD of measurable target lesions, (2) the presence of a new lesion (NL) or (3) the unequivocal PD of non-target disease (NT-PD). We explored the impact of these components, varying over time, on predicting overall survival (OS) in the RECIST database residing at EORTC (Bogaerts et al, 2009). Methods: Data was selected from 12 randomized clinical trials (3530 patients with breast, lung or colorectal cancer). A maximum of 5 target lesions was used to determine the sum of diameters. The following were calculated or assigned at each measurement time t: best response (BR) was best % improvement from baseline up to t (0% if no improvement - 100% if complete response (CR)); tumor growth (TG) was the weekly rate of increase from nadir to t (0 if no increase; irrespective of prior shrinkage), presence of NL (yes/no), and occurrence of NT-PD (yes/no); categories were not mutually exclusive. OS was analyzed by tumor type using a Cox regression model, adjusting for baseline sum, and including BR, TG, presence of NL and NT-PD as time dependent covariates. Results: Thirty-six percent of patients had NL, 26% had NT-PD, 11% achieved CR and 14% did not have shrinkage of target lesions, while 46% experienced TG (median strongest growth per patient of 0.5 mm/week). Regardless of tumor type, the presence of NL (Hazard Ratio (HR) ranging 1.4-2.5), NT-PD (HR 1.2-2.5) and TG (per 1mm/week increase; HR 1.1-1.4) were associated with worse OS, while achieving CR was associated with a longer OS (HR 0.2-0.8). Further analyses exploring the functional shape of the association between BR and TG, and OS are ongoing. This includes putting TG in contrast with the more usual % cutoff defining target PD. Conclusions: All three components of PD according to RECIST are independently strongly associated with OS. Quantification such as this will enable a better understanding of the role of each component (e.g. clinical aspect of NT-PD assessment) in PD evaluation. Work is ongoing to incorporate this information into an updated RECIST with enhanced prediction of subsequent survival.

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