Tumor response as defined by iRECIST in gastrointestinal malignancies treated with PD-1 and PD-L1 inhibitors and correlation with survival

Abstract Background Atypical tumor response patterns during immune checkpoint inhibitor therapy pose a challenge to clinicians and investigators in immuno-oncology practice. This study evaluated tumor burden dynamics to identify imaging biomarkers for treatment response and overall survival (OS) in advanced gastrointestinal malignancies treated with PD-1/PD-L1 inhibitors. Methods This retrospective study enrolled a total of 198 target lesions in 75 patients with advanced gastrointestinal malignancies treated with PD-1/PD-L1 inhibitors between January 2017 and March 2021. Tumor diameter changes as defined by immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) were studied to determine treatment response and association with OS. Results Based on the best overall response, the tumor diameter ranged from − 100 to + 135.3% (median: − 9.6%). The overall response rate was 32.0% (24/75), and the rate of durable disease control for at least 6 months was 30.7% (23/75, one (iCR, immune complete response) or 20 iPR (immune partial response), or 2iSD (immune stable disease). Using univariate analysis, patients with a tumor diameter maintaining a < 20% increase (48/75, 64.0%) from baseline had longer OS than those with ≥20% increase (27/75, 36.0%) and, a reduced risk of death (median OS: 80 months vs. 48 months, HR = 0.22, P = 0.034). The differences in age (HR = 1.09, P = 0.01), combined surgery (HR = 0.15, P = 0.01) and cancer type (HR = 0.23, P = 0.001) were significant. In multivariable analysis, patients with a tumor diameter with a < 20% increase had notably reduced hazards of death (HR = 0.15, P = 0.01) after adjusting for age, combined surgery, KRAS status, cancer type, mismatch repair (MMR) status, treatment course and cancer differentiation. Two patients (2.7%) showed pseudoprogression. Conclusions Tumor diameter with a < 20% increase from baseline during therapy in gastrointestinal malignancies was associated with therapeutic benefit and longer OS and may serve as a practical imaging marker for treatment response, clinical outcome and treatment decision making.

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Use of early primary tumor response to predict overall survival in patients with metastatic RCC undergoing treatment with sunitinib.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.329 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 329-329

Author(s):

E. Abel ◽

S. H. Culp ◽

N. M. Tannir ◽

S. F. Matin ◽

P. Tamboli ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Primary Tumor ◽

Tumor Response ◽

Cox Proportional Hazards ◽

Tumor Diameter ◽

Risk Of Death ◽

Early Primary ◽

Metastatic Sites

329 Background: In metastatic renal cell carcinoma (mRCC) patients treated with sunitinib and the primary tumor in situ, there is minimal predictive data available to help guide clinicians during treatment with targeted therapy. In prior studies, early primary tumor response (PTR) was associated with improved overall PTR, but the effect on overall survival (OS) is unknown. The purpose of our study was to evaluate whether early PTR was associated with improved OS in mRCC patients undergoing treatment with sunitinib. Methods: We reviewed our institutional database to identify patients with mRCC treated with sunitinib with primary tumor in situ. Clinical and pathological data were collected for each patient. Sequential abdominal CT or MRI scans were reviewed to evaluate PTR. Early PTR was defined as ≥ 10% decrease in tumor diameter within the first 90 days of treatment. Univariable and multivariable stepwise Cox proportional hazards regression analysis were performed to identify predictors of OS in these patients. Results: 75 consecutive patients were identified between 2005 and 2009 with a median follow-up of 15 months. 24 patients exhibited an early PTR; median maximum response 23.1% (range: −53.4, −10.2) and decrease in primary tumor diameter at a median of 90.5 days. Early PTR was associated with a decreased risk of death on multivariate analysis (HR: 0.18; 95% CI 0.05, 0.62, p<0.01). In addition, median OS was improved in patients with an early PTR (30.2 vs. 12.7 months). Independent predictors of decreased survival on multivariate analysis included local symptoms, multiple bone metastases, clinical evidence of venous thrombus, LDH > upper limit of normal, and >2 visceral metastatic sites. Conclusions: Early PTR ≥ 10% is associated with improved survival, better response in metastatic sites, and better overall PTR in patients with mRCC. Future studies should consider this variable when evaluating sunitinib in mRCC treatment. [Table: see text]

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The optimal tumor response assessment in patients with HCC after treatment of TACE.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.215 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 215-215 ◽

Cited By ~ 1

Author(s):

E. Jung ◽

J. Kim ◽

E. Yoon ◽

H. Lee ◽

Y. Lee ◽

...

Keyword(s):

Treatment Response ◽

Tumor Response ◽

Univariate Analysis ◽

Significant Risk ◽

Response Assessment ◽

Assessment Method ◽

Hazard Ratios ◽

Different Characteristics ◽

Risk Factors For Survival ◽

Optimal Tumor

215 Background: WHO or RECIST has been considered as suboptimal methods for tumor response assessment in HCC, especially receiving locoregional therapies. Recently, new modified methods having concept of viable tumor has been proposed. Herein we compared the efficacy to assess response and to predict prognosis between WHO, RECIST, EASL, mRECIST in HCC patients receiving TACE. Methods: We retrospectively reviewed 141 HCC patients who were newly diagnosed and received TACE between August 2005 and November 2006. Among them, 98 patients who were available for assessing treatment response were analyzed at 1 month after 2nd TACE. We evaluated intermethod aggreement between methods and assessed the efficacy predicting time to progression (TTP) and overall survival (OS). Results: The results of tumor responses (number of CR/ PR/ SD/ PD) by WHO/ RECIST/ EASL/ mRECIST were 1/ 14/ 74/ 9, 1/ 12/ 77/ 8, 34/ 34/ 25/ 5, 34/ 28/ 31/ 5, respectively. The κvalue of intermethod agreement for EASL vs WHO, EASL vs RECIST, mRECIST vs WHO, and mRECIST vs RECIST was 0.102, 0.088, 0.112 and 0.122, respectively. The κvalue for WHO vs RECIST and EASL vs mRECIST was 0.759 and 0.883 (p=0.00). Hazard ratios for TTP in responders compared with nonresponders were 0.313 (95% CI; 0.19-0.52, p=0.00) for EASL and 0.335 (95% CI; 0.21-0.54, p=0.00) for mRECIST. Hazard ratios for survival in responders compared with nonresponders were 0.208 (95% CI; 0.12-0.37, p=0.00) for EASL and 0.269 (95% CI; 0.15-0.48, p=0.00) for mRECIST. In the univariate analysis, tumor size, infiltrative type, PVT, EASL responder, and mRECIST responder were significant risk factors for survival. Multivariate analysis showed EASL responder (HR 0.165, 95% CI 0.056-0.486, p=0.001) and infiltrative type (HR 4.504, 95% CI 1.579-12.848, p=0.005) were independent predictable factors for survival. Conclusions: The recent proposed methods showed different characteristics from preexisting methods in assessing treatment response and furthermore, responder by EASL method was independent predictor for survival in HCC patients receiving TACE. EASL method should be applied as response assessment method for HCC patients receiving TACE. No significant financial relationships to disclose.

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Adjuvant chemotherapy in nonmetastatic goblet cell carcinomas: A population-based analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16203 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16203-e16203

Author(s):

Valentina Tateo ◽

Elisa Andrini ◽

Davide Campana ◽

Giuseppe Lamberti

Keyword(s):

Multivariate Analysis ◽

Adjuvant Chemotherapy ◽

Lymph Nodes ◽

Univariate Analysis ◽

Population Based ◽

Tumor Diameter ◽

Nodal Involvement ◽

Metastatic Lymph Nodes ◽

Risk Of Death ◽

Metastatic Lymph

e16203 Background: Goblet cell carcinoma (GCC) is a rare mixed endocrine-neuroendocrine tumor arising almost exclusively in the appendix. The optimal management of these patients is still unclear, given GCC rarity and the difficulty in proper pathology diagnosis. We sought to explore the efficacy of adjuvant chemotherapy (ACT) in GCC extracted from the Surveillance, Epidemiology and End Result (SEER) US registry. Methods: Patients with pathology diagnosis of GCC were identified in the SEER registry by the 8243 ICD-09 code. Data about sex, age, tumor stage at diagnosis, number of analyzed and positive lymph-nodes, chemotherapy and survival were collected. Lymph node ratio (LNR) was calculated as the ratio between the number of metastatic lymph-nodes and removed lymph nodes. The best cutoff to predict survival state at 5-year from diagnosis was calculated. The primary endpoint was overall survival (OS). Results: Overall, 1055 GCC patients (51.7% male, median age 57 years) were identified. The median tumor diameter was 20 mm. According to the American Joint Committee on Cancer staging manual 7th edition, 128 patients (12.1%) had nodal involvement (N+): 95 were N1 and 33 were N2, while 66 (6.3%) had distant metastasis (M+). Prognostic LNR cutoff was 0.16. Using this cutoff, LNR was ≤0.16 in 674 patients (63.9%), and > 0.16 in 125 patients (11.8%). The median OS was 232 months (95% confidence interval [95%CI]: 153.4-310.5). Overall, 5-year survival rate (OS-5) was 73.4% (N = 453). At univariate analysis age, tumor diameter, M+, N+, number of lymph nodes removed, number of metastatic lymph nodes and LNR were significantly associated with the risk of death. At multivariate analysis, age, M+, N+, number of removed lymph nodes, and number of metastatic lymph nodes retained their association. After excluding M+ and N+ patients, 897 localized GCC patients (52.8% male) were analyzed. Fifty-five patients (6.1%) received ACT and OS-5 was 83.8% (N = 425). CT was administered more often in tumors with higher histological grade, higher T stage and greater tumor diameter. At the multivariate analysis, only age and number of removed lymph nodes were independently associated with the risk of death. Notably, ACT was not associated with increased survival. Ninety-two patients (57.6% male) had nodal involvement without distant metastases: 73 were N1 and 19 were N2. In 56 patients (60.9%) LNR was ≤0.16, while it was > 0.16 in 35 (38.0%). Thirty-five patients (38%) received ACT, without significant imbalances. OS-5 was 45.2% (N = 28). At univariate analysis, age, N2, number of metastatic lymph nodes and LNR were significantly associated with the risk of death. At multivariate analysis, only the number of metastatic lymph nodes retained its association. Of note, ACT was not associated with increased survival. Conclusions: In GCC, ACT was not associated with increased survival in our population-based analysis, irrespective of nodal involvement.

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OP0098 POLYPHARMACY IS ASSOCIATED WITH A POORER TREATMENT RESPONSE AND INCREASED RISK OF ADVERSE EVENTS IN EARLY RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3213 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 54.1-54

Author(s):

S. Benamar ◽

C. Lukas ◽

C. Daien ◽

C. Gaujoux-Viala ◽

L. Gossec ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Events ◽

Treatment Response ◽

Univariate Analysis ◽

Group Versus ◽

Biological Database ◽

Lower Probability ◽

Research Support ◽

Early Ra ◽

Increased Risk

Background:Polypharmacy is steadily increasing in patients with rheumatoid arthritis (RA). They may interfere with treatment response and the occurrence of serious adverse events. Medications taken by a patient may reflect active comorbidities, whereas comorbidity indices usually used include past or current diseases.Objectives:To evaluate whether polypharmarcy is associated with treatment response and adverse events in an early RA cohort and to establish whether polypharmacy could represent a substitute of comorbidities.Methods:We used data from the French cohort ESPOIR, including 813 patients with early onset arthritis. Patients included the current study had to start their first disease modifying anti-rheumatic drug (DMARD) within 24 months of inclusion in the cohort. Disease activity data were collected at one, five and ten years from the initiation of the first DMARD. For each patient, treatments were collected at baseline and at five years. Medications count included all specialties other than background RA therapy, analgesics/NSAIDs and topicals. Polypharmacy was defined as a categorical variable based on the median and tertiles of distribution in the cohort. Treatment response was assessed by achieving DAS28 ESR remission (REM) at 1 year, 5 years and 10 years from the initiation of the first DMARD. The occurrence of severe adverse events (SAE) was measured by the occurrence of severe infection, hospitalization, or death during the 10-year follow-up. The association between patient’s characteristics and achievement of REM and occurrence of SAE were tested in univariate analysis. A logistic regression model was used to evaluate associations between polypharmacy and REM at 1 year, 5 years and 10 years (we used baseline polypharmacy for the 1-year analysis and five years polypharmacy for the 5- and 10-years analyses). Multivariate adjustment was made for age, sex, BMI, duration of disease, initial DAS28 ESR, initial HAQ, smoking status, rheumatic disease comorbidity index (RDCI).Results:The proportion of patients who achieved REM one year after the initiation of the first DMARD was 32.1% in the polypharmacy according to the median group (patients taken ≥2 medication) versus 67.9% in the non-polypharmacy group (p=0.07). At 5 years after the first DMARD, the proportion of patients with REM was 45.0% in the polypharmacy group versus 56.3% in the non-polypharmacy group (p=0.03). At 10 years the proportion of patients with REM was 32.5% in the polypharmacy group versus 67.5% (p=0.06). Patients who take greater or equal to 2 medications had a 40% lower probability of achieving REM (OR = 0.60 [0.38-0.94] p = 0.03) at 5 years from the first DMARD (if RDCI index was not included in the model). At 10 years, patients receiving multiple medications had a 43% lower probability of achieving REM (OR = 0.57 [0.34-0.94] p = 0.02). SAE incidence was 61 per 1000 patient-years. For patients who developed SAE all causes 71.4% where in the polypharmacy group versus 57.8% were in the non-polypharmacy group (p = 0.03; univariate analysis). These results are no longer significant after adjustment for comorbidities indices.Conclusion:In this early RA cohort, polypharmacy is associated with a poorer treatment response and increased risk of adverse events. Polypharmacy may represent a good substitute of comorbidities for epidemiological studies.Acknowledgements:We are grateful to Nathalie Rincheval (Montpellier) who did expert monitoring and data management and all theinvestigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine; MC. Boissier, Paris-Bobigny; A. Cantagrel, Toulouse; B. Combe, Montpellier; M. Dougados, Paris-Cochin; P. Fardellone and P. Boumier, Amiens; B. Fautrel, Paris-La Pitié; RM. Flipo, Lille; Ph. Goupille, Tours; F. Liote, Paris- Lariboisière; O. Vittecoq, Rouen; X. Mariette, Paris-Bicêtre; P. Dieude, Paris Bichat; A. Saraux, Brest; T. Schaeverbeke, Bordeaux; and J. Sibilia, Strasbourg).The work reported on in the manuscript did not benefit from any financial support. The ESPOIR cohort is sponsored by the French Society for Rheumatology. An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. Pfizer, Abbvie, Lilly and more recently Fresenius and Biogen also supported the ESPOIR cohort.Disclosure of Interests:Soraya Benamar: None declared, Cédric Lukas Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Consultant of: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Pfizer, Novartis and Roche-Chugai, Claire Daien Speakers bureau: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Consultant of: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Cécile Gaujoux-Viala Speakers bureau: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Consultant of: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Grant/research support from: Pfizer, Laure Gossec Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Anne-Christine Rat Speakers bureau: Pfizer, Lilly, Consultant of: Pfizer, Lilly, Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Grant/research support from: Novartis, Pfizer, and Roche-Chugai., Jacques Morel Speakers bureau: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Consultant of: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Grant/research support from: BMS, Pfizer

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Anaemia: A risk factor for death and adverse outcomes following surgery for acute lower limb ischaemia

Vascular ◽

10.1177/17085381211026167 ◽

2021 ◽

pp. 170853812110261

Author(s):

Daniel Perren ◽

Lauren Shelmerdine ◽

Luke Boylan ◽

Craig Nesbitt ◽

James Prentis ◽

...

Keyword(s):

Risk Factor ◽

Cox Model ◽

Univariate Analysis ◽

Adverse Outcomes ◽

Limb Ischaemia ◽

Risk Of Death ◽

Kaplan Meier ◽

Acute Limb Ischaemia ◽

Impact On Survival ◽

Poor Outcomes

Introduction Acute limb ischaemia (ALI) forms a significant part of the vascular surgery workload and carries with it high rates of morbidity and mortality. Anaemia is also common amongst vascular surgical patients and has been linked with poor outcomes in some subgroups. We aimed to assess the frequency of anaemia in patients with ALI and its impact on survival and complications following revascularisation to help direct future efforts to optimise outcomes in this patient group. Methods A retrospective analysis of prospectively collected departmental data on patients undergoing surgical intervention for ALI between 2014 and 2018 was performed. Anaemia was defined as a pre-operative haemoglobin (Hb) of <120 g/L for women and <130 g/L for men. The primary outcome was overall survival, assessed with the Kaplan–Meier estimator, with application of Cox proportional hazard modelling to adjust for confounding covariates. Results There were 158 patients who underwent treatment for ALI: 89 (56.3%) of these were non-anaemic with a mean Hb of 146 (SD = 18.4), and 69 (43.7%) were anaemic with a mean Hb of 106 (SD = 13.4). Anaemic patients had a significantly higher risk of death than their non-anaemic counterparts on univariate analysis (HR = 2.11, 95% CIs, 1.28–3.5, p = 0.0036). There was ongoing divergence in survival up to around 6 months between anaemic and non-anaemic groups. Under the Cox model, anaemia was similarly significant as a predictor of death (HR = 2.15, 95% CIs, 1.17–3.95, p = 0.013), accounting for recorded comorbidities, medication use and blood transfusion. Conclusions Anaemia is a significant and independent risk factor for death following revascularisation for ALI and can be potentially be modified. Vascular surgical centres should ensure they have robust pathways in place to identify and consider treating anaemia. There is scope for further work to assess how to best optimise a patient’s levels of circulating haemoglobin.

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The association between immune-related adverse events and the prognosis of solid cancer patients treated with immunotherapy: a systematic review and meta-analysis

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920980546 ◽

2020 ◽

Vol 12 ◽

pp. 175883592098054

Author(s):

Huilin Xu ◽

Ximing Xu ◽

Wei Ge ◽

Jinju Lei ◽

Dedong Cao

Keyword(s):

Adverse Events ◽

Cancer Patients ◽

Meta Analysis ◽

Progression Free Survival ◽

Cochrane Library ◽

Good Survival ◽

Solid Cancer ◽

Cancer Type ◽

Early Effect ◽

Overall Response

Background: Immune-related adverse events (irAEs) are common during immune checkpoint inhibitor (ICI) treatment and reported to be associated with good survival. This study evaluated the association between onset timing of irAEs and survival of cancer patients treated with ICIs. Methods: Databases including PubMed, Embase, and the Cochrane library were systematically searched to retrieve clinical studies assessing the relationship between irAEs and survival in cancer patients with ICIs. The overall response rate for treatment response and hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were calculated using RevMan 5.3. Subgroup analysis in terms of cancer type, ICIs type, region, specific irAEs, accordingly. Results: A total of 34 studies were included. The HRs for OS and PFS in cancer patients with versus without irAEs were 0.57 [95% confidence interval (CI): 0.44, 0.74; p < 0.0001], and 0.50 (95% CI: 0.37, 0.67; p < 0.00001), respectively. The odds ratio for overall response in cancer patients with irAEs was 4.72 (95% CI: 3.48, 6.40; p < 0.00001) compared with those without irAEs. Subgroup analyses suggested that the prognostic role of irAEs was associated with cancer types and region, but not irAEs types. The landmark analysis of OS revealed that there is a non-proportional (early) effect of irAEs on OS in ICI-treated cancer patients (landmark >12 weeks, HROS = 1.08; 95% CI: 0.89, 1.30; p = 0.46). Conclusion: Our findings suggest that the occurrence of irAEs could be a prognostic factor for cancer patients who were treated with ICIs.

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Risk of Death due to Hepatocellular Carcinoma among Smokers and Ex-smokers. Univariate Analysis of JACC Study Data

The Kurume Medical Journal ◽

10.2739/kurumemedj.51.71 ◽

2004 ◽

Vol 51 (1) ◽

pp. 71-81 ◽

Cited By ~ 9

Author(s):

ITSURO OGIMOTO ◽

AKIRA SHIBATA ◽

YOUICHI KUROZAWA ◽

TAKAYUKI NOSE ◽

TAKESUMI YOSHIMURA ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Univariate Analysis ◽

Study Data ◽

Risk Of Death

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ATRT-26. META-ANALYSIS OF TREATMENT MODALITIES IN METASTATIC ATYPICAL TERATOID/RHABDOID TUMORS IN CHILDREN

Neuro-Oncology ◽

10.1093/neuonc/noaa222.025 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii281-iii281

Author(s):

Reena M Underiner ◽

Mostafa Eltobgy ◽

Joseph R Stanek ◽

Jonathan L Finlay ◽

Mohamed S AbdelBaki

Keyword(s):

Surgical Resection ◽

Meta Analysis ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Substantial Effect ◽

Treatment Modalities ◽

Risk Of Death ◽

Atypical Teratoid ◽

Atypical Teratoid Rhabdoid Tumors ◽

Rhabdoid Tumors

Abstract BACKGROUND Metastatic atypical teratoid/rhabdoid tumors (AT/RT) are aggressive central nervous system tumors that present during infancy and are associated with dismal outcomes. Patients receive multimodal treatment including surgical resection, systemic chemotherapy and one or more of intrathecal chemotherapy (IT), marrow-ablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) and radiation therapy (XRT). While data regarding treatment modalities for AT/RT patients exist, no comprehensive data have been published regarding the metastatic patient population. METHODS We performed a meta-analysis of 1,578 articles published through September 2018, including 44 studies with a total of 123 subjects. Additionally, seven patients were incorporated through chart review of patients treated at Nationwide Children’s Hospital. RESULTS Analysis of 130 patients revealed a 3-year overall survival (OS) of 25%. Age at diagnosis had a significant impact on survival (p=0.0355); 3-year OS for infants < 18 months was 21%; 18–36 months was 26%; and > 36 months was 36%. Location of the primary tumor, metastatic stage and extent of surgical resection did not have significant impact on OS. On univariate analysis, XRT (p<0.0001), IT (p=0.01) and AuHCR (p<0.0001) were found to significantly improve survival. The most substantial effect was noted in patients who received AuHCR (3-year OS of 60% versus 9% in those who did not). On multivariable analysis XRT (p=0.0006), IT (p=0.0124) and AuHCR (p<0.0001) were independently associated with reduced risk of death.

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Downstaging and Resection of Initially Unresectable Hepatocellular Carcinoma with Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody Combinations

Liver Cancer ◽

10.1159/000514313 ◽

2021 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Xiao-Dong Zhu ◽

Cheng Huang ◽

Ying-Hao Shen ◽

Yuan Ji ◽

Ning-Ling Ge ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Partial Response ◽

Adverse Effects ◽

Tyrosine Kinase ◽

Stable Disease ◽

Tumor Response ◽

R0 Resection ◽

Tumor Diameter ◽

Remnant Liver ◽

Unresectable Hepatocellular Carcinoma

Background: Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported. Methods: Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated. Results: Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4–8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8–15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence. Conclusions: Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.

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Significance of Platelet and AFP Levels and Liver Function Parameters for HCC Size and Survival

The International Journal of Biological Markers ◽

10.5301/jbm.5000064 ◽

2014 ◽

Vol 29 (3) ◽

pp. 215-223 ◽

Cited By ~ 14

Author(s):

Brian I. Carr ◽

Vito Guerra ◽

Edoardo G. Giannini ◽

Fabio Farinati ◽

Francesca Ciccarese ◽

...

Keyword(s):

Tumor Size ◽

Blood Platelet ◽

Tumor Diameter ◽

Proportional Hazard ◽

Gamma Glutamyl Transpeptidase ◽

Vein Thrombosis ◽

Risk Of Death ◽

Cox Proportional Hazard ◽

Maximum Tumor Diameter ◽

Glutamyl Transpeptidase

Background Hepatocellular carcinoma (HCC) is a heterogeneous disease with both tumor and liver factors being involved. Aims To investigate HCC clinical phenotypes and factors related to HCC size. Methods Prospectively-collected HCC patients' data from a large Italian database were arranged according to the maximum tumor diameter (MTD) and divided into tumor size terciles, which were then compared in terms of several common clinical parameters and patients' survival. Results An higer MTD tercile was significantly associated with increased blood alpha-fetoprotein (AFP), gamma-glutamyl transpeptidase (GGTP), and platelet levels. Patients with higher platelet levels had larger tumors and higher GGTP levels, with lower bilirubin levels. However, patients with the highest AFP levels had larger tumors and higher bilirubin levels, reflecting an aggressive biology. AFP correlation analysis revealed the existence of 2 different groups of patients: those with higher and with lower AFP levels, each with different patient and tumor characteristics. The Cox proportional-hazard model showed that a higher risk of death was correlated with GGTP and bilirubin levels, tumor size and number, and portal vein thrombosis (PVT), but not with AFP or platelet levels. Conclusions An increased tumor size was associated with increased blood platelet counts, AFP and GGTP levels. Platelet and AFP levels were important indicators of tumor size, but not of survival.

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