Change in body composition and survival in patients with pancreatic cancer.

e15716 Background: The incidence of pancreatic ductal adenocarcinoma (PDAC) is on the rise and continues to have a poor overall survival despite aggressive available treatment strategies. Sarcopenia is prevalent in PDAC patients and is likely caused by both disease and treatment. We hypothesized that ongoing muscle loss during treatment with chemotherapy would be associated with shorter progression-free survival (PFS) and overall survival (OS). Methods: We measured skeletal muscle index at L3 vertebra on baseline follow-up scans in patients with PDAC treated with chemotherapy at our institution. Patients were categorized by percent SMI lost over an 8-week period (<10%, 10-20%, ≥20% loss). We compared PFS and OS between the groups. Results: We included 162 patients with stage I-IV pancreatic cancer. Baseline characteristics are listed in the Table. SMI loss was associated with shortened PFS and OS (p=0.009, p=0.032 respectively) via log-rank test for trend. Even after adjusting for confounders (age, gender, resection status, stage, baseline sarcopenia, treatment and therapy), the relative risk of death (2.0; 95% CI=1.10-3.64, p=0.023), and progression (1.83; 95% CI =1.08-3.10, p =0.024) were higher in those who lost ≥20% SMI. There was no significant association between BMI change or fat change with the survival outcomes. Conclusions: The loss of skeletal muscle during the first 8 weeks of chemotherapy is associated with shortened survival outcomes and is independent of stage and resection status in patients receiving chemotherapy for PDAC. Future studies should seek to understand mechanisms of muscle loss by both tumor and chemotherapy to improve survival in patients with PDAC. Baseline characteristics. [Table: see text]

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Skeletal muscle loss under chemotherapy and its association with survival and systemic treatment toxicity in metastatic colorectal cancer: An AGEO prospective multicenter study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4025 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4025-4025 ◽

Cited By ~ 1

Author(s):

Claire Gallois ◽

Camille Bourillon ◽

Edouard Auclin ◽

Pascal Artru ◽

Astrid Lievre ◽

...

Keyword(s):

Colorectal Cancer ◽

Skeletal Muscle ◽

Multivariate Analysis ◽

Metastatic Colorectal Cancer ◽

Survival Outcomes ◽

Muscle Loss ◽

Skeletal Muscle Index ◽

Nutritional Factors ◽

Multicenter Observational Study ◽

Skeletal Muscle Loss

4025 Background: We showed in a previous work that “Patient Generated-Subjective Global Assessment” (PG-SGA) was independently associated with survival and treatment toxicities in non-pretreated metastatic colorectal cancer (mCRC) patients. We have evaluated here if muscle mass in these patients can provide useful additional information for clinical practice. The objective of the present work was to evaluate the association between baseline sarcopenia, and the variation of the Skeletal Muscle Index (SMI) under treatment with survival and chemotherapy-related toxicities in our population of non-pretreated mCRC patients. Methods: This prospective multicenter observational study enrolled non-pretreated mCRC patients. Measurement of SMI was performed on routine CT scan at day 0 (D0) and day 60 (D60). PG-SGA score and other nutritional factors were collected at D0. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start. Treatment related toxicities were registered according to the NCI CTCAE v4.0. Results: 149 patients were included in eight French centers from 7/2013 to 11/2016. Sarcopenia at baseline was not significantly associated with survival outcomes or chemotherapy-related toxicities. The best cut-point value of SMI variation (between D0 and D60) for OS prediction obtained with a log-rank maximisation method was -14%. The decrease in SMI > 14%, with a median follow-up of 23 months, was significantly associated with shorter PFS (6 vs 9 mo; HR 1.8, 95%CI 1.1-3.1, p = 0.02) and OS (8.5 vs 26 mo; HR 2.4, 95%CI 1.3-4.4, p = 0.004), independently of hypoalbuminemia and malnutrition defined by PG-SGA, in multivariate analysis. 40% of patients with a SMI decrease > 14%, and 22% of patients with a SMI increase or stable or decrease < 14% developed grade ≥ 2 clinical toxicities (OR 3.0, 95%CI 1.2-7.7, p = 0.02), but the difference was not statistically significant in multivariate analysis (OR 2.3. 95%CI 0.8-6.7, p = 0.1). Conclusions: To our knowledge, this study is the first study assessing the association of skeletal muscle loss with survival and treatment toxicities in patients with mCRC prospectively. In our population of non pre-treated mCRC patients, baseline sarcopenia was not associated with poor survival outcomes, but the decrease in SMI > 14% during the first two months of treatment was significantly associated with decreased PFS and OS, independently of other prognostic and nutritional factors.

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Preoperative nutritional risk index and postoperative one-year skeletal muscle loss can predict the prognosis of patients with gastric cancer: a registry based study

10.21203/rs.3.rs-91131/v1 ◽

2020 ◽

Author(s):

Kyung Won Kim ◽

Koeun Lee ◽

Jung-Bok Lee ◽

Taeyong Park ◽

Seungwoo Khang ◽

...

Keyword(s):

Gastric Cancer ◽

Skeletal Muscle ◽

Overall Survival ◽

Regression Analysis ◽

Risk Index ◽

Nutritional Risk ◽

Muscle Loss ◽

Skeletal Muscle Index ◽

Nutritional Risk Index ◽

Skeletal Muscle Loss

Abstract Background: Patients with gastric cancer have increased nutritional risk and experience a significant skeletal muscle loss after surgery. We aimed to determine whether muscle loss during the first postoperative year and nutritional status are indicators for predicting prognosis. Methods: From a gastric cancer registry, a total of 958 patients who received curative gastrectomy followed by chemotherapy for stage 2 and 3 gastric cancer and survived longer than 1 year were investigated. Clinical and laboratory data were collected. Skeletal muscle index (SMI) was assessed based on the muscle area at the L3 level on abdominal computed tomography. Results: Preoperative nutritional risk index (NRI) and postoperative decrement of SMI (dSMI) were significantly associated with overall survival (hazards ratio: 0.972 [95% CI: 0.958-0.986] and 1.058 [95% CI: 1.033-1.085], respectively) in a multivariate Cox regression analysis. Recurrence, tumor stage, comorbidity, and the preoperative muscle and subcutaneous fat area were also significant prognostic indicators. Kaplan-Meier analyses exhibited that patients with higher NRI had a significantly longer survival than those with lower NRI (3-year overall survival: 84.6% vs. 72.9%, P < 0.001). In addition, a significantly better prognosis was observed in a patient group with less decrease of SMI (3-year overall survival: 85.6% vs. 74.5%, P = 0.009). A logistic regression analysis demonstrated that the performance of preoperative NRI and dSMI in mortality prediction was quite significant (AUC: 0.63, P < 0.001) and the combination of clinical factors enhanced the predictive accuracy to the AUC of 0.90 (P < 0.001). This prognostic relevance of NRI and dSMI was maintained in patients experiencing tumor recurrence. Conclusions: Skeletal muscle loss during the first postoperative year and preoperative NRI are predictors of overall survival in stage 2 or 3 gastric cancer patients regardless of relapse. Our results support the potential importance of exercise and nutritional support along with standard treatment.

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Baseline Sarcopenia and Skeletal Muscle Loss During Chemotherapy Affect Survival Outcomes in Metastatic Gastric Cancer

Anticancer Research ◽

10.21873/anticanres.12928 ◽

2018 ◽

Vol 38 (10) ◽

pp. 5859-5866 ◽

Cited By ~ 8

Author(s):

KEIJI SUGIYAMA ◽

YUKIYA NARITA ◽

SEIICHIRO MITANI ◽

KAZUNORI HONDA ◽

TOSHIKI MASUISHI ◽

...

Keyword(s):

Gastric Cancer ◽

Skeletal Muscle ◽

Metastatic Gastric Cancer ◽

Survival Outcomes ◽

Muscle Loss ◽

Skeletal Muscle Loss

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Burden of lymphatic disease predicts efficacy of adjuvant radiation and chemotherapy in FIGO 2018 stage IIICp cervical cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000669 ◽

2019 ◽

Vol 29 (9) ◽

pp. 1355-1360 ◽

Cited By ~ 2

Author(s):

Giorgio Bogani ◽

Daniele Vinti ◽

Ferdinando Murgia ◽

Valentina Chiappa ◽

Umberto Leone Roberti Maggiore ◽

...

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Disease Free Survival ◽

Rank Test ◽

Survival Outcomes ◽

Adjuvant Radiation ◽

Free Survival ◽

Log Rank Test ◽

Disease Free ◽

Positive Lymph Nodes

ObjectiveNodal involvement is one of the most important prognostic factors in cervical cancer patients. We aimed to assess the prognostic role in relation to the burden of nodal disease in stage IIICp cervical cancer.MethodsData on all consecutive patients diagnosed with cervical cancer undergoing primary surgery (radical hysterectomy plus lymphadenectomy) or neoadjuvant chemotherapy followed by radical hysterectomy plus lymphadenectomy, between January 1980 and December 2017, were collected in a dedicated database. Exclusion criteria were: (1) consent withdrawal; (2) synchronous malignancies (within 5 years). Survival outcomes were assessed using Kaplan-Meier and Cox models.ResultsOverall, 177 (14.1%) of 1257 patients with cervical cancer were diagnosed with positive lymph nodes. After a median follow-up of 58 (range 4–175) months, 66 (37.3%) and 37 (20.9%) patients developed recurrent disease and died of disease, respectively. Via multivariate analysis, positive para-aortic nodes (HR 2.62, 95% CI 1.12 to 6.11; p=0.025) and the number of positive nodes (HR 1.06, 95% CI 1.02 to 1.11; p=0.002) correlated with worse disease-free survival. Furthermore, the number of positive nodes (HR 1.06, 95% CI 1.01 to 1.12; p=0.021) correlated with worse overall survival. Number of positive nodes (1, 2 or ≥3) strongly correlated with both disease-free survival (p<0.001, log-rank test) and overall survival (p=0.001, log-rank test). Focusing on patients receiving adjuvant radiation and chemotherapy, the number of positive lymph nodes was associated with response to treatment (p<0.001). Median disease-free survival was 100, 42, and 12 months for patients with one, two, or three or more positive lymph node(s), respectively (p<0.001, log-rank test).ConclusionsIn stage IIICp cervical cancer, adjuvant radiation and chemotherapy provides adequate overall survival in patients diagnosed with only one metastatic node, while survival outcomes are poor in patients with two or more metastatic nodes. This highlights the need for innovative treatments in patients with a high burden of lymphatic disease.

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Continued Weight Loss and Sarcopenia Predict Poor Outcomes in Locally Advanced Pancreatic Cancer Treated with Chemoradiation

Cancers ◽

10.3390/cancers11050709 ◽

2019 ◽

Vol 11 (5) ◽

pp. 709 ◽

Cited By ~ 10

Author(s):

Patrick Naumann ◽

Jonathan Eberlein ◽

Benjamin Farnia ◽

Thilo Hackert ◽

Jürgen Debus ◽

...

Keyword(s):

Skeletal Muscle ◽

Pancreatic Cancer ◽

Weight Loss ◽

Muscle Mass ◽

Muscle Wasting ◽

Statistical Tests ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Skeletal Muscle Index ◽

Poor Outcomes

Background: Surgical resection offers the best chance of survival in patients with pancreatic cancer, but those with locally advanced disease (LAPC) are usually not surgical candidates. This cohort often receives either neoadjuvant chemotherapy or chemoradiation (CRT), but unintended weight loss coupled with muscle wasting (sarcopenia) can often be observed. Here, we report on the predictive value of changes in weight and muscle mass in 147 consecutive patients with LAPC treated with neoadjuvant CRT. Methods: Clinicopathologic data were obtained via a retrospective chart review. The abdominal skeletal muscle area (SMA) at the third lumbar vertebral body was determined via computer tomographic (CT) scans as a surrogate for the muscle mass and skeletal muscle index (SMI) calculated. Uni- and multi-variable statistical tests were performed to assess for impact on survival. Results: Weight loss (14.5 vs. 20.3 months; p = 0.04) and loss of muscle mass (15.1 vs. 22.2 months; p = 0.007) were associated with poor outcomes. The highest survival was observed in patients who had neither cachectic weight loss nor sarcopenia (27 months), with improved survival seen in those who ultimately received a resection (23 vs. 10 months; p < 0.001). Cox regression revealed that either continued weight loss or continued muscle wasting (SMA reduction) was predictive of poor outcomes, whereas a sarcopenic SMI was not. Conclusions: Loss of weight and lean muscle in patients with LAPC is prognostic when persistent. Therefore, both should be assessed longitudinally and considered before surgery.

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Clinical Characteristics and Overall Survival in Patients with Anaplastic Pancreatic Cancer

The American Surgeon ◽

10.1177/000313481408000218 ◽

2014 ◽

Vol 80 (2) ◽

pp. 117-123 ◽

Cited By ~ 3

Author(s):

Clancy J. Clark ◽

Janani S. Arun ◽

Rondell P. Graham ◽

Lizhi Zhang ◽

Michael Farnell ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Pancreatic Ductal Adenocarcinoma ◽

Tumor Stage ◽

Ductal Adenocarcinoma ◽

Rank Test ◽

Poor Overall Survival ◽

Perioperative Morbidity ◽

Log Rank Test ◽

Kaplan Meier

Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months ( P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, ( P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.

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Early Results Of a Phase II Study Of Lenalidomide and Rituximab As Frontline Treatment Of Patients With Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v122.21.4183.4183 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4183-4183

Author(s):

Paolo Strati ◽

Michael J. Keating ◽

Christina Hinojosa ◽

Stefan Faderl ◽

Susan C. Smith ◽

...

Keyword(s):

Pancreatic Cancer ◽

Chronic Lymphocytic Leukemia ◽

Lymphocytic Leukemia ◽

Metastatic Pancreatic Cancer ◽

Categorical Variables ◽

Rank Test ◽

Early Results ◽

Baseline Characteristics ◽

Grade 3

Abstract Introduction The combination of lenalidomide and rituximab is an active treatment for patients (pts) with relapsed Chronic Lymphocytic Leukemia (CLL), with 66% Overall Response Rate (ORR) and a median Progression Free Survival (PFS) of 17.4 months (JCO 2013). We therefore sought to evaluate its efficacy and tolerability in untreated pts. Methods Twenty-five pts with untreated CLL have been enrolled. Rituximab (375 mg/m2 intravenously) was administered weekly during cycle 1 and on day 1 of cycles 3 to 12. Lenalidomide was started on day 9 of cycle 1 at 10 mg orally and administered daily continuously. Each cycle was 28 days. Rituximab was administered for 12 cycles; lenalidomide could continue indefinitely. Response was assessed every 3 cycles by 2008 NCI-WG criteria. Treatment-related toxicity was assessed using Common Terminology Criteria for Adverse Events (version 3.0). The primary end point of this study was ORR. Secondary objectives included PFS and Overall Survival (OS). PFS and OS were calculated using Kaplan-Meier estimates and compared using the log-rank test. Categorical variables were compared using Fisher's exact test (two tailed). Differences were considered significant if p≤.05. Results Baseline characteristics of the 25 pts are shown in Table 1. Twenty-four pts are evaluable for toxicity (one pt was taken off study after only 7 days due to the diagnosis of widely metastatic pancreatic cancer) and 20 for response (2 pts too early, 3 pts early discontinuation). So far 5 pts received 1 cycle, 1 pt received 2 cycles, 6 pts received 3 cycles, 5 received up to 6 cycles and 8 received 12 or more cycles of therapy. ORR by 2008 NCI-WG criteria is 85%, including 2 (10%) complete remission (CR) and 15 (75%) partial remissions (PR). No significant association between ORR and baseline characteristics was observed. At the latest follow-up, the median dose of lenalidomide was 5 (2.5-10) mg and 14 (56%) pts needed at least one interruption because of toxicity. Grade 3-4 toxicities are summarized in Table 2. No episodes of grade 3-4 tumor flare were observed and 7 (29%) pts experienced a grade 1 or 2 tumor flare. Eight (32%) pts have so far discontinued treatment: 1 because of metastatic pancreatic cancer diagnosed after only 1 week on study, 2 because of progressive disease (after 4 months and 13 months), and 5 because of toxicity (skin rash in 3 pts, a deep venous thrombosis in 1 pt, and persistent neutropenia in 1 pt). Two of the 5 pts who discontinued treatment have required subsequent therapy. Twenty-four pts are alive, 1 pt died of metastatic pancreatic cancer after treatment discontinuation. At a median follow-up of 9 (1-17) months, median PFS and median OS have not been reached. Conclusions Our initial experience with the combination of lenalidomide and rituximab as front-line treatment of CLL indicates that this combination is tolerated by the majority of pts and responses are seen in 85% of them. Enrolment in this study is ongoing. Disclosures: O'Brien: CELGENE: Consultancy. Ferrajoli:CELGENE: Research Funding.

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Survival outcomes of advanced pancreatic cancer in an integrative treatment setting: The Cancer Treatment Centers of America experience

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15188 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15188-15188

Author(s):

C. G. Lis ◽

R. D. Levin ◽

R. Neelam ◽

P. G. Vashi ◽

C. A. Lammersfeld ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Treatment ◽

Median Survival ◽

Advanced Pancreatic Cancer ◽

Treatment Protocol ◽

Phase Iii ◽

Definitive Treatment ◽

Comprehensive Cancer Center ◽

Rank Test ◽

Survival Outcomes

15188 Background: In this study, we report the survival outcomes of patients with advanced pancreatic cancer who underwent intra- arterial mitomycin/cisplatin therapy at Cancer Treatment Centers of America (CTCA), a community hospital comprehensive cancer center combining conventional and integrative medical therapies. Methods: At our center, all patients undergo a comprehensive program of nutritional, spiritual, physical, naturopathic, and emotional support while receiving an aggressive conventional treatment protocol. Using data collected by the cancer registry, we identified 114 consecutively treated newly diagnosed cases of invasive pancreatic cancer who underwent definitive treatment between Jan 01 and Dec 05. Results: 26 patients were stage III and 88 were stage IV. The median age was 58 years (range 31 to 81 years). 55 patients were selected for intra-arterial therapy with mitomycin/cisplatin. These patients had a PS of 2 or better and either had no metastatic lesions or a single localized liver metastasis. 16 patients in this cohort received radiotherapy. The 59 other patients underwent a variety of therapies. Intra-arterially treated patients had a median survival of 369 days and a 2-year cumulative survival of 19%. Patients not treated with intra-arterial therapy had a median survival of 249 days and a 2-year survival of 11%. Univariate survival analysis found that patients undergoing intra-arterial therapy had significantly better survival outcomes compared to patients undergoing different therapies (Log rank test P = 0.04). The table compares the survival outcomes of recent phase III investigations on first line therapies for pancreatic cancer with those at CTCA. Conclusion: Currently, the published clinical trial data in advanced pancreatic indicates a one-year survival ranging from less than 10% to 28%. Consequently, the survival outcomes of patients undergoing therapy at our center warrant further investigation. [Table: see text] No significant financial relationships to disclose.

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Study of genotypic variations and protein expression of the xCT subunit of cystine/glutamate transporter in pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.210 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 210-210

Author(s):

T. J. Huang ◽

D. Li ◽

Y. Li ◽

S. P. Kar ◽

S. Krishnan ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Protein Expression ◽

Cox Regression ◽

Performance Status ◽

Glutamate Transporter ◽

Supporting Evidence ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Increased Risk

210 Background: The plasma membrane xCT cystine-specific subunit of the cystine/glutamate transporter contributes to chemotherapy resistance in pancreatic cancer by regulating intracellular glutathione levels and protecting cancer cells against oxidative stress. We previously noted that the rs7674870 single nucleotide polymorphism (SNP) of xCT correlated with overall survival in pancreatic cancer and may be predictive of platinum resistance. There are no data regarding xCT protein expression in pancreatic cancer or the functional significance of this SNP. Methods: Paraffin-embedded core and surgical biopsy tumor specimens from 49 patients with metastatic pancreatic adenocarcinoma were analyzed by immunohistochemistry (IHC) using an xCT specific antibody (Novus Biologicals). xCT protein IHC expression scores (product of intensity and percentage of staining cells) were analyzed in relation to overall survival and genotype of the patients using the one factor ANOVA test, Kaplan-Meier plot, log-rank test, and Cox regression analysis. Overall survival was measured from the date of diagnosis to the date of death or last follow-up. Results: Positive xCT expression was detected in 38 (78%) of the 49 samples, and 9 (18%) patients had high levels of expression. High xCT expression was associated with lower overall survival as compared with low expression (5.1 months versus 8.8 months; p = 0.119). In a multivariate Cox regression model with adjustment for prognostic parameters of age, sex, performance status and CA19-9 level, high xCT expression was associated with a 2.1-fold increased risk of death (p = 0.096). Performance status also correlated with overall survival (p = 0.027). Preliminary analysis on the genotype-phenotype association (n = 12) indicated that xCT expression was higher with the TT genotype than the TC/CC genotype (p = 0.115), which is consistent with the previous observation that the TT genotype was associated with reduced survival. Conclusions: These data provide supporting evidence for a possible role of cystine/glutamate transporter xCT subunit in pancreatic cancer progression and survival. Further pharmacogenomic and clinicopathologic studies are ongoing. No significant financial relationships to disclose.

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Resminostat in advanced hepatocellular carcinoma (HCC): Overall survival subgroup analysis of prognostic factors in the SHELTER trial.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15088 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15088-e15088 ◽

Cited By ~ 5

Author(s):

Michael Bitzer ◽

Tom M. Ganten ◽

Marcus A. Woerns ◽

Jens T. Siveke ◽

Matthias M. Dollinger ◽

...

Keyword(s):

Overall Survival ◽

Lower Risk ◽

Vascular Invasion ◽

Line Treatment ◽

Second Line ◽

Monotherapy Group ◽

First Line ◽

Treatment Groups ◽

Risk Of Death ◽

Baseline Characteristics

e15088 Background: Previously published results of the phase I/II SHELTER study demonstrated efficacy and safety of the novel pan-HDAC inhibitor resminostat in second-line treatment of HCC patients (pts) who had progressed under first-line sorafenib. As patient baseline characteristics might influence treatment outcome, an analysis of their potential influence on overall survival (OS) was performed. Methods: 45 pts with advanced-stage HCC and centrally confirmed radiologic progression under first-line sorafenib were included in a multi-center, two-arm trial. Resminostat was administered either alone or in combination with sorafenib. A Cox proportional-hazards model was used to evaluate the interaction between baseline characteristics and the effect of the two treatment groups on overall survival. Results: In the combination group, pts with Child-Pugh-A, ECOG 0 or absence of vascular invasion had a statistically significant lower risk of death compared to pts with Child-Pugh-B (HR 0.19, 95% CI 0.06-0.55), ECOG 1 (HR 0.15, 95% CI 0.05-0.44), or vascular invasion (HR 0.37, 95% CI 0.15-0.93), respectively. For pts with BCLC-B there was a strong trend, although not statistically significant, of a lower risk of death when compared to pts with BCLC-C (HR 0.43, 95% CI 0.13-1.49). Etiology, prior TACE therapy, extrahepatic spread and interval between first- and second-line treatment had no impact on overall survival in this study. Similar findings were observed in the monotherapy group. Comparing the impact of these baseline characteristics in the combination and monotherapy group, no statistically significant different influence on OS between both treatment groups was observed. Conclusions: Resminostat in combination with sorafenib provides a substantial OS benefit (median OS of 8.1 months) for advanced HCC patients who had developed progressive tumor disease under first-line sorafenib therapy. Subgroup analysis of patient baseline characteristics revealed a significant influence of Child-Pugh index, ECOG classification, and vascular invasion on overall survival, whereas e.g. the interval between first- and second-line treatment had no impact on overall survival. Clinical trial information: NCT00943449.

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