Difference In Progression-free Survival Rates Research Articles

Microwave Ablation versus Surgical Resection for US-detected Multifocal T1N0M0 Papillary Thyroid Carcinoma: A 10-Center Study.

Background Microwave ablation (MWA) is currently under preliminary investigation for the treatment of multifocal papillary thyroid carcinoma (PTC) and has shown promising treatment efficacy. Compared with surgical resection (SR), MWA is minimally invasive and could preserve thyroid function. However, a comparative analysis between MWA and SR is warranted to draw definitive conclusions. Purpose To compare MWA and SR for preoperative US-detected T1N0M0 multifocal PTC in terms of overall and 1-, 3-, and 5-year progression-free survival rates and complication rates. Materials and Methods In this retrospective study, 775 patients with preoperative US-detected T1N0M0 multifocal PTC treated with MWA or SR across 10 centers between May 2015 and December 2021 were included. Propensity score matching (PSM) was performed for patients in the MWA and SR groups, followed by comparisons between the two groups. The primary outcomes were overall and 1-, 3-, and 5-year progression-free survival (PFS) rates and complication rates. Results After PSM, 229 patients (median age, 44 years [IQR 36.5-50.5 years]; 179 female) in the MWA group and 453 patients (median age, 45 years [IQR 37-53 years]; 367 female) in the SR group were observed for a median of 20 months (range, 12-74 months) and 26 months (range, 12-64 months), respectively. MWA resulted in less blood loss, shorter incision length, and shorter procedure and hospitalization durations (all P < .001). There was no evidence of differences in overall and 1-, 3-, or 5-year PFS rates (all P > .05) between MWA and SR (5-year rate, 77.2% vs 83.1%; P = .36) groups. Permanent hoarseness (2.2%, P = .05) and hypoparathyroidism (4.0%, P = .005) were encountered only in the SR group. Conclusion There was no evidence of a significant difference in PFS rates between MWA and SR for US-detected multifocal T1N0M0 PTC, and MWA resulted in fewer complications. Therefore, MWA is a feasible option for selected patients with multifocal T1N0M0 PTC. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Georgiades in this issue.

A retrospective study of transarterial chemoembolization (TACE) combined with lenvatinib compared with TACE monotherapy for BCLC B2 stage hepatocellular carcinoma.

The present study aimed to compare the efficacy and safety of combination therapy with lenvatinib (Len) plus transarterial chemoembolization (TACE) and TACE alone in patients with Barcelona Clinic Liver Cancer (BCLC) B2 stage hepatocellular carcinoma (HCC). A total of 66 patients with BCLC B2 stage HCC were retrospectively reviewed in the present study, of which 34 patients received Len + TACE, while 32 patients received TACE alone between May 2018 and May 2020. Survival outcome, tumor response and adverse events (AEs) were compared between the two treatment groups. The 6-month, 1- and 2-year overall survival (OS) rates were significantly higher in the Len + TACE group (97.1, 85.3 and 76.3%, respectively) compared with those in the TACE group [(93.8, 81.1 and 45.4%, respectively); hazard ratio (HR), 0.395; 95% confidence interval (CI), 0.180-0.867; P=0.023], but no significant difference in progression-free survival rate was observed between the two groups (HR, 0.815; 95% CI, 0.437-1.520; P=0.510). Patients receiving Len + TACE demonstrated a higher objective response rate compared with those receiving TACE alone (64.7 vs. 34.4%; P=0.014). Therefore, Len + TACE combination therapy was associated with increased OS and tumor response compared with that of TACE monotherapy in patients with BCLC B2 stage HCC. However, large-scale, multicenter, prospective studies are needed to further confirm these results.

Upfront autologous haematopoietic stem-cell transplantation versus carfilzomib–cyclophosphamide–dexamethasone consolidation with carfilzomib maintenance in patients with newly diagnosed multiple myeloma in England and Wales (CARDAMON): a randomised, phase 2, non-inferiority trial

Standard-of-care treatment for patients with newly diagnosed multiple myeloma is bortezomib-based induction followed by high-dose melphalan and autologous haematopoietic stem-cell transplantation (HSCT) and lenalidomide maintenance. We aimed to evaluate whether an immunomodulatory-free carfilzomib-based induction, consolidation, and maintenance protocol without autologous HSCT was non-inferior to the same induction regimen followed by autologous HSCT and maintenance. CARDAMON is a randomised, open-label, phase 2 trial in 19 hospitals in England and Wales, UK. Newly diagnosed, transplantation-eligible patients with multiple myeloma aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 received four 28-day cycles of carfilzomib (56 mg/m2 intravenously on days 1, 2, 8, 9, 15, and 16), cyclophosphamide (500 mg orally on days 1, 8, and 15), and dexamethasone (40 mg orally on days 1, 8, 15, and 22; KCd), followed by peripheral blood stem cell mobilisation. Patients with at least a partial response were randomly assigned (1:1) to either high-dose melphalan and autologous HSCT or four cycles of KCd. All randomised patients received 18 cycles of carfilzomib maintenance (56 mg/m2 intravenously on days 1, 8, and 15). The primary outcomes were the proportion of patients with at least a very good partial response after induction and difference in progression-free survival rate at 2 years from randomisation (non-inferiority margin 10%), both assessed by intention to treat. Safety was assessed in all patients who started treatment. The trial is registered with ClinicalTrials.gov (NCT02315716); recruitment is complete and all patients are in follow-up. Between June 16, 2015, and July 8, 2019, 281 patients were enrolled, with 218 proceeding to randomisation (109 assigned to the KCd consolidation group [99 of whom completed consolidation] and 109 to the HSCT group [104 of whom underwent transplantation]). A further seven patients withdrew before initiation of carfilzomib maintenance (two in the KCd consolidation group vs five in the HSCT group). Median age was 59 years (IQR 52 to 64); 166 (59%) of 281 patients were male and 115 (41%) were female. 152 (71%) of 214 patients with known ethnicity were White, 37 (17%) were Black, 18 (8%) were Asian, 5 (2%) identified as Mixed, and 2 (1%) identified as other. Median follow-up from randomisation was 40·2 months (IQR 32·7 to 51·8). After induction, 162 (57·7%; 95% CI 51·6 to 63·5) of 281 patients had at least a very good partial response. The 2-year progression-free survival was 75% (95% CI 65 to 82) in the HSCT group versus 68% (95% CI 58 to 76) in the KCd group (difference -7·2%, 70% CI -11·1 to -2·8), exceeding the non-inferiority margin. The most common grade 3-4 events during KCd induction and consolidation were lymphocytopenia (72 [26%] of 278 patients who started induction; 15 [14%] of 109 patients who started consolidation) and infection (50 [18%] of 278 for induction; 15 [14%] of 109 for consolidation), and during carfilzomib maintenance were hypertension (20 [21%] of 97 patients in the KCd consolidation group vs 23 [23%] of 99 patients in the HSCT group) and infection (16 [16%] of 97 patients vs 25 [25%] of 99). Treatment-related serious adverse events at any point during the trial were reported in 109 (39%) of 278 patients who started induction, with infections (80 [29%]) being the most common. Treatment-emergent deaths were reported in five (2%) of 278 patients during induction (three from infection, one from cardiac event, and one from renal failure) and one of 99 patients during maintenance after autologous HSCT (oesophageal carcinoma). KCd did not meet the criteria for non-inferiority compared with autologous HSCT, but the marginal difference in progression-free survival suggests that further studies are warranted to explore deferred autologous HSCT in some subgroups, such as individuals who are MRD negative after induction. Cancer Research UK and Amgen.

Survival Rate in Lung Adenocarcinoma with Mutation of the EGFR Gene with Tyrosine Kinase Inhibitor Treatment

Background: EGFR mutation is a genetic disorder that is often observed and examined in Non-Small Cell Lung Carcinoma. EGFR mutation detection aims to predict sensitivity to EGFR-TKI and acts as first-line therapy. Targeted therapy with EGFR-TKI can increase the survival rate of patients with Non-Small Cell Lung Cancer compared to chemotherapy. This study aims to obtain data on the survival rate of patients with Non-Small Cell Lung Carcinoma who received targeted therapy at H. Adam Malik Hospital. &#x0D; Methods: This study is a descriptive study with a retrospective cohort design carried out at the Oncology Polyclinic at RSUP H Adam Malik Medan for 5 years, from January 2014 to December 2018. The subjects of this study were all patients with lung cancer type adenocarcinoma who had received therapy with generation 1 or 2 EGFR TKI. &#x0D; Results: 99 patients were included as subjects of this study. From the study, the most influential factors on lung cancer were gender, age, and smoking addiction. The study consisted of 60.6% male, 92.9% of the respondents aged 40 years and over, 56.5% active, and 43.4% passive smokers and 41.4% of the respondents with severe Brinkman index. The 30-month survival rate of EGFR-TKI (Gefitinib) patients treated with NSCLC Adenocarcinoma (Gefitinib) from 2014 to 2018 at H. Adam Malik Hospital Medan was 6.3% with a median survival of 7 months. The duration of progression-free survival in patients receiving Erlotinib therapy was 6.6 months (6.6 ± 2.51 months), while the length of progression-free survival for patients treated with Gefitinib was 9.1 months (9.1 ± 6.9 months). The results of statistical tests showed that there was no difference in progression-free survival rate between those who received Erlotinib and Gefitinib (P = 0.82). &#x0D; Conclusion: The 30-month survival rate of lung adenocarcinoma patients treated with EGFR-TKI from 2014 to 2018 was 6.1% with a median survival of 7 months. Those who received Erlotinib therapy experienced Progression-Free Survival for 6.6 months and those who received Gefitinib experienced Progression-Free Survival for 9.1 months.

Abstract P5-13-07: Implications of body mass index (BMI) on the biological and clinical effects of endocrine therapy and abemaciclib in the neoadjuvant setting

Abstract Background: Our prior analysis of the MONARCH2/3 trials showed no difference in progression-free survival rates according to BMI in patients treated with abemaciclib and endocrine therapy for hormone receptor-positive, HER2-negative advanced breast cancer (Franzoi et al, JNCI 2021). However, a statistically inferior overall response rate with abemaciclib and endocrine therapy was observed in patients with BMI ≥25. In the present study, we examined the impact of baseline BMI on mean KI67% changes, achievement of complete cell cycle arrest (CCCA) and clinical and radiological responses in patients included in the phase II NEOMONARCH trial, which randomized patients to receive a 2-week initial treatment with either abemaciclib, letrozole, or abemaciclib and letrozole followed by 14 weeks of the combination of abemaciclib and letrozole as neoadjuvant therapy for hormone receptor-positive, HER2-negative early-stage breast cancer patients. Patients and methods: This is an exploratory, individual patient-level, post-hoc analysis of the NEOMONARCH study. Data was assessed through a research proposal submission in the Vivli platform. Patients were classified according to baseline BMI into underweight/normal weight (BMI &amp;lt;25 kg/m2) and overweight/obese (BMI≥25 kg/m2). The primary endpoint was the percent change in Ki67 expression from baseline to 2 weeks of treatment. The analysis was performed using the Fisher exact test for categorical variables and the Wilcoxon rank-sum test and its multisample generalization (Kruskal-Wallis test) for continuous variables. CCCA was analyzed as per the main study definition: patients with Ki67 % ≤2.7 after 2 weeks of treatment. Results were considered significant if p-value &amp;lt;0.05. Results: Out of 263 patients included in NEOMONARCH, A total of 222 patients (84.4%) had BMI information available, of whom 6 (2.7%) were underweight, 75 (33.8%) had normal weight, 77 (34.7%) were overweight and 64 (28.8%) were obese. Regarding baseline characteristics, patients with BMI ≥25 were predominantly Caucasian (p=0.001) and presented more with other histologies of breast cancer (p=0.007). There was no significant difference regarding baseline tumor grade or size, node status, ER/PR status, age, and Ki67% value at baseline according to BMI. In the overall cohort, mean Ki67% changes at 2 weeks were similar between the two BMI groups: - 19 (IQR -27.8 to -10.4) for patients with BMI &amp;lt;25 and -17.2 (IQR -26.8 to -11) for patients with BMI ≥25 (p=0.760). The proportion of patients achieving CCCA after 2 weeks of treatment was numerically higher for patients with BMI &amp;lt;25 vs ≥25 (56% vs 43%, respectively; p=0.096). Mean Ki67% reduction at 2 weeks was significantly higher for patients receiving the combination of abemaciclib + letrozole when compared to letrozole alone or abemaciclib alone, regardless of BMI. There was also no significant difference regarding radiological response (p=0.366) or clinical response (p=0.261) according to BMI at the end of the treatment period (16 weeks). Conclusions: In this exploratory analysis, BMI categorized by the threshold of 25 did not significantly impact KI67% changes or the proportion of patients achieving CCA after the initial 2 weeks of neoadjuvant therapy with abemaciclib, letrozole, or their combination. Moreover, BMI did not have an impact on radiological and clinical response rates after 14 weeks of treatment with letrozole and abemaciclib. Although limited by the small sample size, these results are reassuring that the combination of letrozole and abemaciclib appears to be active in the early setting regardless of baseline BMI. Citation Format: Maria Alice Franzoi, Matteo Lambertini, Marcello Ceppi, Marco Bruzonne, Evandro de Azambuja. Implications of body mass index (BMI) on the biological and clinical effects of endocrine therapy and abemaciclib in the neoadjuvant setting [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-07.

Usefulness of albumin–globulin ratio as a clinical prognostic factor in patients with thyroid cancer treated with radioiodine

Albumin-globulin ratio (AGR), which is calculated by dividing serum albumin by serum globulin, is considered as a cancer-related inflammation biomarker. Although the prognosis of many solid cancers has been shown to be associated with AGR, there are no studies to demonstrate the association between the prognosis of thyroid cancer and AGR. The purpose of this study is to reveal the relationship between AGR and overall survival (OS) in patients with thyroid cancer who received radioactive iodine therapy (RIT). Eighty-eight patients with thyroid cancer who had received RIT for the first time in our institution were included. The values before RIT were adopted as initial measurements for serum albumin, globulin, and thyroglobulin (Tg) and used for analysis. Patients were divided into two groups based on the AGR value. We analyzed the relationship between clinical factors and treatment outcome. The median follow-up period was 92.4months (range: 30.1-173.9months). The 5-year OS and progression-free survival (PFS) were 94% and 54%, respectively. Seventeen patients (< 65years, 8; and ≥ 65years, 9) died during the follow-up period. Low AGR was significantly associated with OS in both univariate and multivariate analyses (p = 0.0059 and p = 0.0120, respectively). As the 5-year OS was as high as 94%, there was no significant difference in survival rate between the two groups during the first 5years. However, there seemed to be a remarkable difference in 10years after the first RIT. On the other hand, Tg was significantly associated with PFS in both univariate and multivariate analyses (p = 0.0016 and p = 0.0441, respectively). In patients under the age of 65, the PFS rate was significantly lower in the low AGR group (p < 0.0001), while there was no difference in PFS rate between the two AGR groups in patients aged 65years or older. AGR may be used as a prognostic factor in relatively younger patients with thyroid cancer treated with radioiodine, while it may be less useful in the older. Overall, it may be an independent prognostic factor for long-term survival in those with thyroid cancer.

Radiotherapy of extranodal low-grade follicular and marginal zone lymphomas: long-term follow-up of 159 patients.

To evaluate clinical, histopathologic, and radiation (RT) dose parameters in patients with extranodal low-grade (ENLG) non-Hodgkin lymphoma (NHL) and their possible impact on local control (LC) and survival. The medical records of 159 patients with 181 histologically confirmed ENLG-NHL lesions treated at our institution were reviewed retrospectively. The predominant histological subtype (73%) was marginal zone lymphoma (MZL). Common lesion sites were the gastrointestinal tract (GIT; 33%), skin (26%), and orbit (21%). The majority of patients (88%) presented with stageI/II disease. Thirty-three (20%) lesions were treated with reduced-dose RT (≤30.6 Gy) and 148 lesions (80%) with conventional-dose RT (>30.6 Gy), with an overall median dose of 39.6 Gy (range 4-63). The median follow-up period was 72months. The 10-year local control (LC), Progression-free survival (PFS), and overall survival (OS) rates were 96, 65, and 82%, respectively. Higher overall response rate (ORR; 98% vs. 94%, p = 0.001) and complete response rate (CRR; 95% vs. 73%, p = 0.001) were observed in patients treated with conventional-dose regimens than in those treated with reduced-dose regimens. Ten-year PFS (p = 0.90) and OS (p = 0.40) was similar between the two dose groups. RT was well tolerated in both dose groups, with no grade4/5 toxicities. In the multivariate analysis, RT dose and timing (upfront or salvage) were related to LC, whereas age, histology, and complete response (CR) to RT were associated with PFS. Patient age and radiation field size impacted OS. RT is an effective and curative local treatment for early-stage FL and MZL at conventional and reduced radiation doses. Conventional-doses seems to be associated with local response improvement, without significant differences in PFS rates. Age, histology, andresponse to RT mayinfluence thePFS.

Randomised Phase 2 study of lapatinib and vinorelbine vs vinorelbine in patients with HER2\u2009+\u2009metastatic breast cancer after lapatinib and trastuzumab treatment (KCSG BR11-16)

BackgroundThe continuum of anti-HER2 agents is a standard treatment of HER2 + metastatic breast cancer (MBC). This study evaluated the efficacy of lapatinib plus vinorelbine in patients progressed on both trastuzumab and lapatinib treatments.MethodsA total of 149 patients were randomly assigned to lapatinib with vinorelbine (LV) (n = 75; lapatinib, 1000 mg daily; vinorelbine 20 mg/m2 D1, D8 q3w) or vinorelbine (V) (n = 74; 30 mg/m2 D1, D8 q3w). The primary endpoint was progression-free survival (PFS) rate at 18 weeks.ResultsThe median number of previous anti-HER2 therapies was 2 (range 2–5). There was no significant difference in PFS rate at 18 weeks between LV and V arms (45.9% vs 38.9%, p = 0.40). ORR was 19.7% in LV arm, and 16.9% in V arm (p = 0.88). PFS and OS did not differ between two arms (LV vs V; median PFS, 16 vs 12 weeks, HR = 0.86, 95% CI 0.61–1.22; median OS, 15.0 vs 18.9 months, HR = 1.07, 95% CI 0.72–1.58). Toxicity profiles were similar in both arms and all were manageable.ConclusionsLapatinib plus vinorelbine treatment was tolerable; however, it failed to demonstrate the clinical benefits over vinorelbine alone in patients with HER2 + MBC after progression on both trastuzumab and lapatinib.Clinical trial registrationClinicalTrials.gov number NCT01730677.

Abstract P6-17-23: Randomized phase II study of lapatinib plus vinorelbine versus vinorelbine in patients with HER2 positive metastatic breast cancer progressed after lapatinib and trastuzumab treatment

Abstract Background The continuum of anti-HER2 agents is regarded as a standard strategy for HER2 positive metastatic breast cancer patients who had progressed disease with anti-HER2 agent- containing treatments. However, there has been lack of data on which agents should be continued and how long continuous anti-HER2 therapies would be effective. This study was aimed to evaluate the efficacy of lapatinib plus vinorelbine in HER2 positive metastatic breast cancer patients who had progressed on both trastuzumab and lapatinib treatments. Methods A total of 149 patients were randomly assigned to lapatinib with vinorelbine (LV) (n=75; laptinib, 1000mg daily ; vinorelbine 20mg/m2 D1,D8 q3w) or vinorelbine alone (V) (n=74; 30mg/m2 D1,D8 q3w). The stratification factors were followings; 1) visceral metastasis, 2) previous response to lapatinib treatment, CR+PR vs. SD ≥ 12 weeks. The primary endpoint was progression free survival (PFS) rate at 18 weeks. The secondary endpoints were objective response rate (ORR), PFS, and overall survival (OS). Results : Both arms were well balanced in various clinical factors. The median number of previous anti-HER2 therapies were 2 (range 2-5). There was no significant difference in PFS rate at 18 weeks between LV and V arms (44.0% vs 36.5%, p=0.44). ORR was 19.7% in LV arm and 16.9% in V arm (p=0.881). PFS and OS did not differ between two arms (LV vs V; median PFS, 16weeks vs 12 weeks, HR= 0.86, 95% CI 0.61-1.22, p=0.41; median OS, 15.0 months vs 18.9 months, HR= 1.07, 95% CI 0.72-1.58, p=0.72). In subgroup analysis, there was no difference in PFS and OS between two arms according to previous response to lapatinib (median PFS, CR+PR vs. SD ≥ 12 weeks, 12.1weeks vs.17.4 weeks; HR= 1.242, 95% CI 0.881-1.751, p=0.215; median OS, 14.9 months vs. 19.4 months; HR= 1.179, 95% CI 0.797-1.744, p=0.41). Most common adverse events in both arms were neutropenia which was more often observed in V arm (55% vs 73%, p=0.03). Overall, the profiles of adverse events were similar in both arms and all were manageable. Conclusion Lapatinib plus vinorelbine treatment was tolerable, however, it did not demonstrate the clinical benefits compared to vinorelbine alone in HER2 positive metastatic breast cancer patients after progression on both trastuzumab and lapatinib. Citation Format: Sim SH, Park IH, Jung KH, Kim S-B, Ahn J-H, Lee K-H, Im S-A, Im Y-H, Park YH, Sohn JH, Kim YJ, Lee S, Kim H-J, Chae YS, Park K-H, Nam B-H, Lee KS, Ro J. Randomized phase II study of lapatinib plus vinorelbine versus vinorelbine in patients with HER2 positive metastatic breast cancer progressed after lapatinib and trastuzumab treatment [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-23.

Impact of inflammatory marker levels one month after the first-line targeted therapy initiation on progression-free survival prediction in patients with metastatic clear cell renal cell carcinoma.

Progression-free survival of first-line targeted therapy greatly influences the survival of patients with metastatic renal cell carcinoma. We evaluated whether post-treatment inflammatory markers and lactate dehydrogenase levels had impacts on progression-free survival prediction in addition to those of conventional predictors. Two hundred and fifteen patients whose tumors were clear cell type and in whom first-line targeted therapies could be continued for >1 month were evaluated. Pretreatment clinical factors, pathological factors and laboratory data 1 month after targeted therapy initiation-including inflammatory markers (neutrophil count, neutrophil-to-lymphocyte ratio and C-reactive protein) and lactate dehydrogenase-were reviewed. To identify progression-free survival predictors, multivariate analyses were done. The 1-year progression-free survival rate was 47%. Female gender, Karnofsky performance status <80%, time from diagnosis to systemic treatment <12 months, pretreatment C-reactive protein >3.0 mg/dl and post-treatment neutrophil-to-lymphocyte ratio >3.0 were independent predictors for progression-free survival. In contrast, neither C-reactive protein increase nor neutrophil-to-lymphocyte ratio increase after targeted therapy initiation were independent predictors. Pretreatment lactate dehydrogenase, post-treatment lactate dehydrogenase and lactate dehydrogenase decline were not independent predictors. When all patients were stratified by these independent factors into three groups (0 risk vs. 1 or 2 risks vs. 3 or more risks), there were significant differences in progression-free survival rates between the groups (P < 0.0001). Furthermore, there were also significant differences in overall survival rates between the groups (P < 0.0001). Integration of post-treatment neutrophil-to-lymphocyte ratio value with pretreatment factors may lead to the establishment of effective predictive model for disease progression in patients with metastatic clear cell renal cell carcinoma who received first-line targeted therapies.

MP16-07 USEFULNESS OF INFLAMMATORY MARKER DYNAMICS ONE MONTH AFTER THE FIRST-LINE TARGETED THERAPY INITIATION FOR PFS PREDICTION IN PATIENTS WITH METASTATIC CLEAR CELL RENAL CELL CARCINOMA

MP16-07 USEFULNESS OF INFLAMMATORY MARKER DYNAMICS ONE MONTH AFTER THE FIRST-LINE TARGETED THERAPY INITIATION FOR PFS PREDICTION IN PATIENTS WITH METASTATIC CLEAR CELL RENAL CELL CARCINOMA

Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: the AFFIRM study

The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC. Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis. Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% [95% confidence interval (CI) 17.2-34.4] for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2-30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89-9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62-9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74-1.36). The response rates were 49.1% (95% CI 39.7-58.6) and 45.9% (95% CI 36.4-55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%). No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity. NCT00851084, www.clinicaltrials.gov, EudraCT 2008-004178-41.

MP70-03 OPTIMAL TIMING OF HORMONAL THERAPY FOR PROSTATE-SPECIFIC ANTIGEN RECURRENCE AFTER RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Advanced II1 Apr 2014MP70-03 OPTIMAL TIMING OF HORMONAL THERAPY FOR PROSTATE-SPECIFIC ANTIGEN RECURRENCE AFTER RADICAL PROSTATECTOMY Kazuhiro Matsumoto, Ryuichi Mizuno, Nobuyuki Tanaka, Hiroki Ide, Masanori Hasegawa, Masaru Ishida, Nozomi Hayakawa, Yota Yasumizu, Masayuki Hagiwara, Satoshi Hara, Eiji Kikuchi, Akira Miyajima, Ken Nakagawa, Yosuke Nakajima, So Nakamura, Jun Nakashima, and Mototsugu Oya Kazuhiro MatsumotoKazuhiro Matsumoto More articles by this author , Ryuichi MizunoRyuichi Mizuno More articles by this author , Nobuyuki TanakaNobuyuki Tanaka More articles by this author , Hiroki IdeHiroki Ide More articles by this author , Masanori HasegawaMasanori Hasegawa More articles by this author , Masaru IshidaMasaru Ishida More articles by this author , Nozomi HayakawaNozomi Hayakawa More articles by this author , Yota YasumizuYota Yasumizu More articles by this author , Masayuki HagiwaraMasayuki Hagiwara More articles by this author , Satoshi HaraSatoshi Hara More articles by this author , Eiji KikuchiEiji Kikuchi More articles by this author , Akira MiyajimaAkira Miyajima More articles by this author , Ken NakagawaKen Nakagawa More articles by this author , Yosuke NakajimaYosuke Nakajima More articles by this author , So NakamuraSo Nakamura More articles by this author , Jun NakashimaJun Nakashima More articles by this author , and Mototsugu OyaMototsugu Oya More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2202AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The routine use of prostate-specific antigen (PSA) monitoring after radical prostatectomy (RP) has frequently identified men with biochemical disease recurrence (BCR). However, the appropriate timing and type of therapy for them remain controversial. The present study was undertaken to examine biochemical progression in patients who received salvage hormonal therapy (HT) for BCR after RP, and to determine the optimal timing for the administration of HT. METHODS The study population consisted of 156 patients who underwent RP during the period of 1991-2007 and received HT for BCR. The starting point was the timing of RP, and the endpoint was biochemical progression (castration-resistance) after the combined androgen blockade HT. The mean follow-up period was 8.1 years. RESULTS First, we excluded 18 patients with persistent PSA (≥0.2 ng/mL) after RP from an analysis below to remove any bias due to the inhomogeneous backgrounds because their prognoses were significantly poorer compared with 138 patients whose PSA nadirs had reached <0.2 ng/mL. In the remaining 138 patients, multivariate analysis showed that Gleason score ≥8 (p=0.010, hazard ratio (HR) 3.02), and PSA-doubling time (DT) <6 months (p=0.001, HR 7.39) were independently associated with subsequent biochemical progression after HT. Using these two variables (Gleason score and PSA-DT), we defined patients with both risk factors as ′high-risk′ for biochemical progression. Next, to determine the optimal timing for HT administration, we divided the patients according to the PSA level at the initiation of HT. In the 27 high-risk patients with both risk factors, the PSA cutpoint of 1.0 ng/mL at the initiation of HT showed a significant difference in progression-free survival rates (Figure 1a, p=0.023). On the other hand, in the 111 non-high-risk patients, the cutpoint of PSA 4.0 ng/ml demonstrated a significant difference between the two cohorts (Figure 1b, p=0.034). CONCLUSIONS The findings indicated that for high-risk patients (Gleason score ≥8 and PSA-DT <6 months), salvage HT for BCR after PSA nadir (< 0.2 ng/mL) should be started before the PSA level exceeds 1.0 ng/mL, otherwise there is a significant risk of subsequent biochemical progression after HT. Meanwhile, the induction of salvage HT could be delayed in non-high-risk patients. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e807 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Kazuhiro Matsumoto More articles by this author Ryuichi Mizuno More articles by this author Nobuyuki Tanaka More articles by this author Hiroki Ide More articles by this author Masanori Hasegawa More articles by this author Masaru Ishida More articles by this author Nozomi Hayakawa More articles by this author Yota Yasumizu More articles by this author Masayuki Hagiwara More articles by this author Satoshi Hara More articles by this author Eiji Kikuchi More articles by this author Akira Miyajima More articles by this author Ken Nakagawa More articles by this author Yosuke Nakajima More articles by this author So Nakamura More articles by this author Jun Nakashima More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Immunophenotype and intermediate‐high international prognostic index score are prognostic factors for therapy in diffuse large B‐cell lymphoma patients

The development of gene expression profiling and tissue microarray techniques have provided more information about the heterogeneity of diffuse large B-cell lymphoma (DLBCL), enabling categorization of DLBCL patients into 3 prognostic groups according to cell origin (but independently from the International Prognostic Index [IPI] score): germinal center (GCB), activated B-cell (ABC), and not classified (NC) diffuse large B-cell lymphoma. This study investigated the role of immunohistochemical discrimination between GCB and ABC&NC-DLBCL subtypes in identifying those high-risk patients who may benefit from a more aggressive first-line therapeutic approach. From February 2003 to August 2006, 45 newly diagnosed DLBCL patients, with IPI≥2, were considered eligible for this study: 13 had a GCB, 8 an ABC, and 24 a NC-DLBCL. GCB patients received 6 courses of rituximab, cyclophophosphamide, doxorubicin, vinicristine, and prednisone (R-CHOP) chemotherapy, with a subsequent, autologous stem cell transplantation in case of partial response. All ABC and NC-DLBCL patients received 6 R-CHOP cycles and autologous stem cell transplantation. Complete response rate for each treatment arm was 84.6% for GCB and 89.7% for ABC&NC-DLBCL (P = .50), with a continuous complete response rate of 81.8% and 84.6%, respectively (P = .59). Projected 4-year overall survival is 100% for GCB and 82% for ABC&NC patients (P = .12). Progression-free survival is 77% and 79% (P = .7), respectively. The autologous stem cell transplantation consolidation in the ABC&NC-DLBCL subtypes induced the same rate of complete response (and similar progression-free survival rate) compared with GCB-DLBCL. In ABC&NC-DLBCL patients the authors observed a complete response rate of 89.7% vs. 84.6% in the GCB-DLBCL subset, without any significant difference in progression-free survival rate.

Comparison of Response Over 6 Years Between Patients with Chronic Myeloid Leukemia Who Received Imatinib as Initial Therapy and Those Who Received Imatinib as Secondary Therapy.

Abstract 4281 ObjectiveTo compare responses in a single center over 6 years between patients with Philadelphia-positive chronic myeloid leukemia (CML) who received imatinib as initial therapy and those who received imatinib as secondary therapy. Patients and MethodsWe reviewed 171 cases of patients with Philadelphia chromosome (Ph)-positive CML who received imatinib for 72 months: 73 patients in an initial therapy group (time from diagnosis of CML less than 6 months) and 98 patients in a secondary therapy group (time from diagnosis of CML greater than 6 months). ResultsCumulative rates of complete cytogenetic response (CCyR) at 6, 12, and 36 months after imatinib treatment in the initial therapy group and secondary therapy group were 75%, 89% and 96%, and 48%, 77% and 84%, respectively (P=0.0002). The median time to CCyR in initial and secondary therapy groups was 6 months (95%CI, 3.3–8.3) and 9 months (95%CI, 6.4–11.6), respectively (P=0.0002). Cumulative rates of major molecular response (MMoR) at 9, 12 and 18 months after imatinib treatment in initial therapy and secondary therapy groups were 26%, 42% and 49%, and 16%, 25% and 36%, respectively (P=0.048). The median time to MMoR in initial and secondary therapy groups was 19 months (95%CI, 11.7–26.3) and 36 months (95%CI, 19.7–52.4), respectively (P=0.048). Estimated rates of freedom from progression to accelerated phase (AP) and blastic phase (BP) in initial and secondary therapy groups were 99% and 89%, respectively (P=0.08). Estimated 6-year progression-free survival (PFS) rates in cases with CCyR and without CCyR were 93% and 62%, respectively (P=0.0012). Estimated 6-year event-free survival (EFS) rates in initial and secondary therapy groups were 96% and 68%, respectively (P=0.04). The event was defined as progression to accelerated AP and BP, loss of CCyR or CHR. ConclusionThe time to CCyR and MMoR in the initial therapy group was significantly shorter than that in the secondary therapy group. There was no difference in PFS rates between the two groups in the 72-month long-term follow-up. The EFS rates indicated that patients receiving imatinib as initial therapy achieved more stable remissions than those receiving it as secondary therapy. Disclosures:No relevant conflicts of interest to declare.

Tumor Size Predicts Control of Benign Meningiomas Treated with Radiotherapy

OBJECTIVE: The goal of this study was to evaluate the effect of postoperative residual tumor size on the outcomes for patients with incompletely resected benign meningiomas who underwent radiotherapy (RT). METHODS: Fifty-four patients with incompletely resected benign meningiomas received postoperative RT between 1984 and 1995. Surgery consisted of partial resection for 43 patients (80%) and biopsy for 11 (20%). All patients underwent postoperative imaging (using computed tomography and/or magnetic resonance imaging), and the median residual tumor size was 3.5 cm (in greatest dimension). Thirty-eight tumors (69%) were <5 cm, and 17 (31%) were > or =5 cm. The median RT dose was 54 Gy (range, 45-60 Gy), delivered in daily fractions of 1.8 to 2 Gy. The median follow-up period was 55 months. RESULTS: The 5-year actuarial progression-free survival (PFS) rate for the entire group was 76%. The only significant predictor of PFS rates was residual tumor size. Large residual tumors (> or =5 cm) exhibited a worse 5-year PFS rate than did small tumors (<5 cm) (40 versus 93%, P < 0.0001). When analyzed as a continuous variable, residual tumor size remained a significant prognostic factor. Age, sex, tumor histological features, tumor location, timing of treatment (immediate versus delayed), extent of resection, and RT dose (<54 Gy versus > or =54 Gy) did not reach prognostic significance. The difference in PFS rates for small and large residual tumors translated into a significant difference in 5-year cause-specific survival rates (65 versus 97%, P = 0.01). CONCLUSION: For incompletely resected benign meningiomas treated with RT, residual tumor size is the most significant predictor of tumor control. Small residual tumors are well controlled with conventional RT doses and techniques. In contrast, more aggressive therapies should be considered for large tumors.

Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas

The optimum treatment of nonresectable low-grade gliomas of childhood remains undecided. There has been increased interest in the use of chemotherapy for young children, but little information concerning the long-term efficacy of such treatment. Seventy-eight children with a mean age of 3 years (range 3 months-16 years) who had newly diagnosed, progressive low-grade gliomas were treated with combined carboplatin and vincristine chemotherapy. The patients were followed for a median of 30 months from diagnosis, with 31 patients followed for more than 3 years. Fifty-eight children had diencephalic tumors, 12 had brainstem gliomas, and three had diffuse leptomeningeal gliomas. Forty-four (56%) of 78 patients showed an objective response to treatment. Progression-free survival rates were 75 ± 6% at 2 years and 68 ± 7% at 3 years. There was no statistical difference in progression-free survival rates between children with neurofibromatosis Type 1 and those without the disease (2-year, progression-free survival 79 ± 11% vs. 75 ± 6%, respectively). The histological subtype of the tumor, its location, and its maximum response to chemotherapy did not have an impact on the duration of disease control. The only significant prognostic factor was age: children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 ± 7% compared with a rate of 39 ± 21% in older children (p &lt; 0.01). Treatment with carboplatin and vincristine is effective, especially in younger children, in controlling newly diagnosed progressive low-grade gliomas.