Important Prognostic Factors For Progression-free Survival Research Articles

Exploring the association of ADAM17 expression with survival in patients with non-small cell lung cancer.

The A disintegrin and metalloprotease (ADAM) family is involved in many vital cellular events, from proliferation to migration, and accumulated evidence suggests its increased expression in malignant tumors. In this study, we investigated ADAM17 expression in non-small cell lung cancer (NSCLC) and its relationship with clinicopathological factors and survival. Immunohistochemical staining of ADAM expression was performed in 108 patients with NSCLC and in 54 control cases with no known malignant diagnosis. Association between ADAM17 expression, clinicopathological factors, and survival were analyzed. The Kaplan-Meier method was used for survival analysis. ADAM17 was lowly expressed in 89 (82.4%) and highly expressed in 19 (17.6%) of the patients with NSCLC. In univariate analysis, high ADAM17 expression, lymphovascular invasion, stage, and treatment response significantly affected progression-free survival (PFS) and overall survival (OS) (p < 0.05). Multivariate analysis also showed that high ADAM17 expression, lymphovascular invasion, stage, and treatment response were important prognostic factors for PFS and OS (p < 0.05). Our study revealed that high ADAM17 expression significantly associated with OS and PFS in patients with NSCLC. ADAM17 may potentially be the area of a new targeted treatment strategy in NSCLC. Thus, routine evaluation of ADAM17 expression in patients with NSCLC may be a future consideration.

Prognostic role of docetaxel-induced reduction of free testosterone serum levels in metastatic prostate cancer patients.

144 Background: We have recently demonstrated that a salvage therapy with carboplatin plus weekly docetaxel is effective in docetaxel-refractory prostate cancer (PC) and interferes with testosterone biosynthesis (Reuter et al.; Oncol Res &amp; Treat. 2018, 41 (suppl.1): p.10). In this study, the impact of docetaxel monotherapy on free and total testosterone serum levels (fT, TT) and the prognostic role of fT and TT were analyzed in mPC patients. Methods: 62 consecutive mPC patients were treated with at least two cycles of docetaxel (75 mg/m2 q3w; 50 mg/m2 q2w, or 35 mg/m2 q1w) until disease progression, occurrence of intolerable adverse effects or completion of the planned cycle number. Efficacy measures were done following PCWG2 recommendations. FT and TT were measured before and during chemotherapy. Results: At the current analysis (August 31, 2020), the median follow-up time was 21.2 months. Response of prostate-specific antigen (PSAR; ≥50% PSA reduction) was observed in 42/62 (67.7%) and 12/36 (33.3%) patients with measurable disease exhibited a partial remission (PR). Median progression-free survival (PFS) for all patients was 8.1 months (CI 95% 3.6, 12.5) and median overall survival (OS) was 25.7 months (CI 95% 19.4, 32.1). The most common reversible grade 3/4 toxicity was leukopenia/neutropenia (29/33.9%). Median fT and TT serum levels were reduced below the detection limit during docetaxel treatment (fT: from 0.34 pg/mL to &lt; 0.01 pg/mL and TT: from 0.12 to &lt; 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified PSAR &gt; 50%, fT reduction of 100% and number of organs involved as independent prognostic risk factors for PFS. Furthermore, fT reduction of 100% and FT nadir values &lt; 0.01 pg/mL were independent prognostic risk factors for OS (p &lt; 0.05). Conclusions: These data demonstrate that fT is an important prognostic factor for PFS and OS in mPC patients.

Real‐world outcomes with bortezomib‐containing regimens and lenalidomide plus dexamethasone for the treatment of transplant‐ineligible multiple myeloma: a multi‐institutional report from the Canadian Myeloma Research Group database

Bortezomib-containing regimens (BCRs) represented standard, first-line therapy for transplant-ineligible multiple myeloma (TIMM) in Canada until the introduction of lenalidomide and low-dose dexamethasone (Ld). However, little comparative data exist to inform the selection of regimens. We assessed the outcomes for TIMM patients treated with cyclophosphamide, bortezomib and dexamethasone or prednisone (CyBorD/P), bortezomib, melphalan and prednisone (VMP), bortezomib and dexamethasone or prednisone (VD/P) and lenalidomide and low-dose dexamethasone (Ld) using the Canadian Myeloma Research Group database. Of 1156 TIMM patients evaluated, 82% received bortezomib combinations while 18% received Ld. Median progression-free survival (PFS) was 21·0, 21·1, 13·2 and 28·5months (P=0·0002) and median overall survival (OS) was 52·0, 63·6, 30·8 and 65·7months (P<0·0001) in the CyBorD/P, VMP, VD/P and Ld groups respectively. There was no significant difference in PFS and OS between the two triplet bortezomib regimens (VMP and CyBorD/P). Ld was associated with a longer PFS but not a significantly superior OS to date. Outcomes with the bortezomib-steroid doublet were inferior (VD/P). However, multivariable analysis identified features related to disease biology as the most important prognostic factors for PFS and OS. Such factors, as well as those affecting the physician's choice of regimen, are likely to influence the results observed with different regimens. This study demonstrated real-world outcomes in TIMM similar to those reported in clinical trials.

Abstract No. 535 Drug-eluting bead transarterial chemoembolization versus conventional transarterial chemoembolization in colorectal liver metastasis: efficacy and safety and prognostic factors

To evaluate the efficacy, safety and prognostic factors of drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE) in the treatment of colorectal liver metastasis (CRLM). This study retrospectively analyzed 75 patients with CRLM who received DEB-TACE treatment (36 cases) or cTACE treatment (39 cases) between January 2016 and December 2017. Local control, survival outcome and complications were compared between the two groups. Univariate and multivariate analyses of prognostic factors affecting progression-free survival (PFS) and total survival (OS) were performed. The median duration of follow-up in the two groups was 10.49 months (range, 0.5-22). The median PFS and OS in DEB-TACE group were 10.0 months and 13.0 months, respectively, and in the cTACE group were 6.0 months and 8.5 months (P = 0.009 and 0.008). The 3-, 6- and 12-month survival rates in DEB-TACE group were 100.0%, 94.4%, and 55.6%, respectively. The survival rates in the cTACE group were 92.3%, 71.8%, and 35.9%, respectively. There was no statistically significant difference in the 3-month survival rate (P = 0.083), but significant statistical difference in the 6-month and 12-month survival rates (P = 0.008 and 0.030). Univariate and multivariate survival analyses showed that different treatment methods, tumor size and tumor number were important prognostic factors for PFS and OS. DEB-TACE has advantages over cTACE in prolonging PFS and OS in CRLM patients. Different treatment methods, tumor number and tumor size are important prognostic factors affecting PFS and OS. However, further randomized, multicenter and prospective trials are still needed to confirm the results of this study.Tabled 1Local tumor control and survival of two treatment cohorts.ParameterDEB-TACE (N=36)cTACE (N=39)Z, χ2or t valuePmRECIST (%)Z = 8.8160.032 CR16.7 (6/36)12.8 (5/39) PR41.7 (15/36)15.4 (6/39) SD25.0 (9/36)30.8 (12/39) PD16.7 (6/36)41.0 (16/39)Response rate (%)83.3 (30/36)59.0 (23/39)χ2 = 5.5390.025PFS (months)χ2 = 6.8970.009 Median10.06.0 IQR6.0-14.02.0-10.0OS (months)χ2 = 7.1280.008 Median13.08.5 IQR9.0-16.05.0-12.5OS rate (%) 3 months100.0 (36/36)92.3 (36/39)t = 1.7800.083 6 months94.4 (34/36)71.8 (28/39)t = 2.7410.008 12 months55.6 (20/36)35.9 (14/39)t = 2.2140.030 Open table in a new tab

840P - Prognostic value of free testosterone (FT) levels during salvage chemotherapy with carboplatin plus weekly docetaxel in metastatic castration- and docetaxel-resistant prostate cancer (mDRPC)

ABSTRACT Background Recent data suggest that carboplatin plus weekly docetaxel (DC) is an effective salvage therapy in DRPC. Carboplatin, docetaxel and steroids all interfere with testosterone biosynthesis and/or metabolism. In this study the impact of DC treatment on testosterone serum levels was analyzed. Methods Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 71 consecutive DRPC pts were treated with at least two cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel at a dose of 35 mg/m iv for one hour on days 1, 8, (15) plus prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. FT was measured before (n = 44) and during carboplatin/docetaxel chemotherapy (n = 38). Results Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 34/71 (47.9%) patients. At the time of the current analysis the median follow-up time was 14.5 months and 47/71 patients had died. Median progression-free survival (PFS) for all patients was 6.9 months (CI 95% 4.3, 13.6) and median overall survival (OS) was 18.0 months (CI 95% 10.4, 25.6). Median FT serum levels were 3.0 pmol/L before (n = 43) and below the RIA detection limit of Conclusion These data demonstrate for the first time that testosterone is an important prognostic factor for PFS and OS in mDRPC patients receiving chemotherapy. Disclosure C.W.M. Reuter: Minor consulting fees from Sanofi Aventis, Amgen, V. Grunwald: Consulting fees from Novartis, All other authors have declared no conflicts of interest.

Prognostic value of extracapsular spread of regional lymph nodes in nasopharyngeal carcinoma with 3DCRT based on magnetic resonance imaging

Objective To evaluate the prognostic value of the extracapsular spread (ECS) of regional lymph nodes in nasopharyngeal carcinoma (NPC) based on magnetic resonance imaging. Methods A retrospective review was performed for 477 previously untreated patients with NPC who were treated in Yuebei People′s Hospital from January 2009 to December 2013.Univariate and multivariate survival analyses were performed to identify the prognostic value of ECS in NPC. Results There were 216 patients with ECS and 261 patients without ECS, and the median survival of the two groups of patients was 38.5 months and 39.0 months, respectively. The 3-year overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates of the patients with ECS versus those without ECS were 81.9% versus 90.7%, 65.8% versus 85.0%, 87.8% versus 95.8%, and 80.3% versus 92.9%, respectively (all P=0.000). The univariate analysis showed that N stage and ECS were important prognostic factors for OS, PFS, LRFS, and DMFS in NPC patients (P=0.000-0.004), and T stage and TNM stage were associated with OS, PFS, and DMFS (all P=0.000). The multivariate analysis using the Cox regression model showed that T stage was an independent prognostic factor for the survival of NPC patients, and ECS was an important prognostic factor for PFS, LRFS, and DMFS. Conclusion ECS of regional lymph nodes is a risk factor for local recurrence or distant metastasis in patients with NPC. Key words: Nasopharyngeal neoplasms/three-dimensional radiotherapy; Neoplasm metastasis, lymph nodes; Prognosis

Bortezomib-based chemotherapy for patients with multiple myeloma: a single center experience

To evaluate the efficacy and safety of bortezomib-based chemotherapy for 80 patients with multiple myeloma (MM). A total of 80 cases with a median age of 57 (range: 25-78) years were enrolled in the study. Bortezomib-based regimens included VD (bortezomib and dexamethasone) and PAD (bortezomib, doxorubicin and dexamethasone). 16 of the 80 patients received autologous or allo-hematopoietic stem cell transplantation (HSCT). The overall response (OR) rate was 80%, including a complete response (CR) of 46.3%. After a median follow-up of 25 months, the 1-year and 2-year overall survival (OS) was 81.4% and 72.9%, and the 2-year progression-free survival (PFS) was 76% and 62.5%, respectively. The 2-year OS and PFS were 100% and 73.9 % in patients with HSCT, while both were 66% (P=0.029) and 58.7% (P=0.447) in patients without HSCT. In univariate analysis, Durie-Salmon group, ISS stage, CR and very good partial response (VGPR), and HSCT were prognostic factors for OS. Gender and extramedullary plasmacytomas were important prognostic factors for PFS. Multivariate analysis by Cox regression revealed that CR and VGPR, Durie-Salmon group A, and HSCT were prognostic factors for better OS; while male and patients without extramedullary plasmacytomas were prognostic factors for longer PFS. MM patients could benefit from bortezomib-based chemotherapy with satisfactory efficacy and safety. HSCT could improve the OS for young MM patients.

908P - Prognostic Value of Free Testosterone (FT) Levels During Salvage Chemotherapy with Carboplatin Plus Weekly Docetaxel in Metastatic Castration- and Docetaxel-Resistant Prostate Cancer (MDRPC)

ABSTRACT Background Recent data suggest that carboplatin plus weekly docetaxel (DC) is an effective salvage therapy in DRPC. Carboplatin, docetaxel and steroids all interfere with testosterone biosynthesis and/or metabolism. In this study the impact of DC treatment on testosterone serum levels was analyzed. Methods Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 71 consecutive DRPC pts were treated with at least two cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel at a dose of 35 mg/m iv for one hour on days 1, 8, (15) plus prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. FT was measured before (n = 44) and during carboplatin/docetaxel chemotherapy (n = 38). Results Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 34/71 (47.9%) patients. At the time of the current analysis the median follow-up time was 14.5 months and 47/71 patients had died. Median progression-free survival (PFS) for all patients was 6.9 months (CI 95% 4.3, 13.6) and median overall survival (OS) was 18.0 months (CI 95% 10.4, 25.6). Median FT serum levels were 3.0 pmol/L before (n = 43) and below the RIA detection limit of Conclusion These data demonstrate for the first time that testosterone is an important prognostic factor for PFS and OS in mDRPC patients receiving chemotherapy. Disclosure C.W.M. Reuter: Minor consulting fees from Sanofi Aventis, Amgen, V. Grunwald: Consulting fees from Novartis, All other authors have declared no conflicts of interest.

High‐dose chemotherapy in relapsed or refractory Hodgkin lymphoma patients: a reappraisal of prognostic factors

High-dose chemotherapy (HDCT) has a consolidated role in the treatment of patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical results of 97 HL patients who underwent HDCT for refractory (62 patients) or relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to 2009. Treatment included high-dose carmustine, etoposide, cytarabine and melphalan in 84 patients and high-dose idarubicin and melphalan in 13 patients with subsequent peripheral hemopoietic stem cells transplant. Outcomes were evaluated in terms of progression-free survival (PFS) and overall survival (OS). In order to identify prognostic factors for outcome, a multivariate analysis for age, sex, disease status (refractory/relapsed), disease stage, B symptoms, presence of extranodal involvement, bulky disease, elevated lactate dehydrogenase, number of previous chemotherapy lines, remission status before transplant, 18F-fluoro-deoxy-d-glucose positron emission tomography ((18) FDG-PET) status before and after transplant was done. A clinical response was achieved in 91% of patients, with complete remissions in 76/97 patients. With a median follow-up of 45 months (range 1-164 months), 5-year PFS and OS were 64% and 71%, respectively. Remission status after induction therapy, 18F-fluoro-deoxy-d-glucose positron emission tomography status before and after transplant were the most important prognostic factors for PFS and OS in univariate or multivariate analyses. HDCT is able to induce a high remission rate and a prolonged PFS in more than 50% of the patients with refractory and relapsed HL.

Results of autologous transplants for lymphomas from a tertiary cancer center in India

7106 Background: Autologous stem cell transplanation is the standard of care for patients of relapsed and refractory non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). We report the results of transplants in lymphomas from our center and role of possible prognostic factors. Methods: All 50 consecutive patients who underwent transplant for HL (70%) and NHL (30%) from August 1994- August 2008 were included in this retrospective study. Fifty eight percent of patients received BEAM (carmustine, etoposide, ara-c and melphalan), 30% LACE (lomustine, ara-c, cyclophosphamide and etoposide), 8% ICE (ifosfamide,carboplatin and etoposide) and 4% high dose melphalan (200mg/m2) conditioning regimens. Seventy eight percent of patients received peripheral blood stem cells (PBSC), 8% bone marrow (BM) and 14% both PBSC and BM. Prognostic factors evaluated for progression free survival (PFS) were serum albumin level and body mass index (BMI) at the time of transplant, stage at diagnosis and source of stem cells, while for over all survival (OS), status of disease at transplant was also included. Results: The median time to transplant was 2.25 years from the time of diagnosis. The median age at transplant was 25 years. Seventy four percent of patients were male. At the time of transplant, thirty two percent were in complete remission (CR), 50% in partial remission (PR) and 18% had refractory disease (RD). The median serum albumin and BMI at the time of transplant were 4 g/dl and 22.5 kg/m2 respectively. The best disease response rate was 86% (CR+PR) in patients evaluable for response. Thirteen patients relapsed at a median interval of 11 months post transplant. The cumulative probability of OS and progression free survival PFS at 5 years were 40% and 34% respectively for the whole group. Multivariate analysis using cox regression identified serum albumin greater than 4 g/dl and those receiving PBSC grafts as independently associated with improved OS and PFS. Conclusions: These data provide the first published report of outcomes of autologous transplants in lymphomas from India. Our data suggests that serum albumin level at the time of transplant and stem cell source are important prognostic factors for PFS and OS. No significant financial relationships to disclose.

Clinical and molecular determinants of survival in pancreatic cancer patients treated with second line chemotherapy: results of an Italian/Swiss multicenter survey

4622 Background: The impact on survival of palliative second-line therapy in pancreatic cancer has not been clarified and clinical/molecular predictive factors are needed in order to decide which therapeutic regimens may be effective. Methods: Clinical records of 160 Gemcitabine resistant/refractory pancreatic cancer patients (pts) treated in 11 medical oncology departments in Italy and Switzerland were reviewed. All pts received a second line regimen from June 1997 to February 2006. There were 99 males, 61 females, median age 62 years (range 34–78) and median ECOG performance status (PS): 1 (range 0–2). 16 different salvage regimens were administered consisting of monotherapy with fluoropyrimidines in 59% of cases and combinations of platinum- salts/fluoropyrimidines in 36%. Fluoropyrimidines combinations with bevacizumab, irinotecan and mitomycin C were administered in the remaining 5%. ERCC-1 expression was examined by performing immunohistochemical staining in pts treated with platinum-salts. Results: Second line chemotherapy produced partial responses (PR) in 16 (10%) and stable disease (SD) in 40 pts (25%) by RECIST criteria. The median progression free survival (PFS) was 2.65 months. Multivariate analysis revealed that the most important prognostic factor for PFS was PS at the beginning of second line therapy (Second line PFS PS=0–1 vs PS=2: 78 days vs 48 days, p&lt;0.05, log-rank test). Pts who had responded (PR) to first-line Gemcitabine were more likely to respond or attain stable disease after second-line treatment, with a PFS of 2.6 vs 1.6 months (p&lt;0.05, log-rank test). The overall survival (OS) for all evaluable pts was 11.5 months and 1-year survival was 45%. Among 57 pts treated with platinum-containing doublets, a low ERCC1 level (28/57 pts) was highly predictive of longer survival (11.9 versus 9.9 months, p&lt;0.05 log-rank test). Conclusions: These results suggest that fluoropyrimidine-based salvage regimens have marginal activity and should be considered only in pts with a good PS who have responded to first line chemotherapy. ERCC-1 expression should be further evaluated as a predictive test to select patients who may benefit from platinum/fluoropyrimidine salvage regimens. No significant financial relationships to disclose.

Treatment outcomes with first and second line chemotherapy in advanced and metastatic pancreatic cancer patients

14107 Background: Recent advances in the treatment of pancreatic cancer might influence the management of locally advanced and metastatic disease, nonetheless prognosis remains dismal (1-year survival rates: 24%). The impact on survival of palliative second-line therapy is hotly debated. Methods: We retrospectively reviewed the clinical records of 103 pancreatic cancer patients admitted to San Camillo/Forlanini Hospital (Rome, Italy) and the Oncology Institute of Southern Switzerland during the period June, 1997 to August, 2005 [60 males, 43 females, median age 65 years (range 43–80); median ECOG performance status (PS): 1]. All patients received Gemcitabine as single agent (90%) or in combination with Oxaliplatin (10%) as upfront therapy. A total of 12 fluoropyrimidine-based salvage regimens were administered to 46 patients in the second line setting. Best supportive care was selected in 57 patients after failing first line therapy. Results: Of 103 evaluable patients, first line chemotherapy produced overall tumor growth control of partial response (PR) and stable disease(SD) by RECIST criteria of 52.4% with a median progression free survival (PFS) of 4.6 months. Multivariate analysis revealed that the most important prognostic factor for PFS was the patient’s PS, as patients with PS of 1–2 at diagnosis had significantly worse results than patients with PS = 0 (First line PFS: 110 days vs 193 days, p&lt;0.05). Baseline CA19–9 and number of metastatic sites were not independent prognostic factors for better first-line PFS. PR was observed in 8/46 patients (17.3%) who received second line chemotherapy, SD in 10 (21.7%), and 28 patients progressed (61%). Median overall second line PFS was 3.2 months. Patients who had responded to first-line Gemcitabine were more likely to respond or attain stable disease with second-line treatment, with a PFS of 5.6 vs 2.85 months (p&lt;0.05). The overall survival for all evaluable patients was 8.4 months. 1-year survival was 52% for patients treated with second line therapy. Conclusions: These results are consistent with historical studies and suggest that fluoropyrimidine-based salvage regimens have marginal but definite activity and should be considered in patients who have responded to first line chemotherapy with an optimal PS. No significant financial relationships to disclose.

A randomised study comparing standard dose carboplatin with chlorambucil and carboplatin in advanced ovarian cancer

A total of 161 previously untreated patients with FIGO stage III or IV epithelial ovarian cancer were randomised after surgery to receive six courses of either carboplatin 400 mg m-2 alone (Arm A) or carboplatin 300 mg m-2 with chlorambucil 10 mg day-1 for 7 days (Arm B). The median progression free survival (PFS) was similar: arm A: 45 weeks; arm B: 61 weeks (P = 0.830). Multivariate Cox regression analysis showed that the extent of residual disease and performance status were the most important prognostic factors for PFS. Fifty-two per cent of patients received dose escalations based on nadir blood counts, and 89% of all dose adjustments were made according to protocol. Failure to achieve a significant degree of leucopenia was associated with worse progression free survival (P less than 0.001). A total of 29.4% of patients fall into this category. The median survival was similar in both arms, i.e. 75 weeks. It is unlikely that there is any major clinical advantage to adding chlorambucil to single agent carboplatin for the management of advanced ovarian cancer, but whether used in combination or a single agent, the dose of carboplatin should be sufficient to cause at least grade I leucopenia. This may best be achieved by determining the initial dose based on renal function, and then adjusting subsequent doses according to nadir blood counts.