Tumor Growth Rate Decline Despite Progressive Disease May Predict Improved Nivolumab Treatment Outcome in mRCC: When RECIST Is Not Enough

Treatment response is usually assessed by the response evaluation criteria in solid tumors (RECIST). These criteria may not be adequate to evaluate the response to immunotherapy, considering the peculiar patterns of response reported with this therapy. With the advent of immunotherapy these criteria have been modified to include the evaluation of the peculiar responses seen with this type of therapy (iRECIST criteria), including pseudoprogressions and hyperprogressions. Tumor growth rate (TGR) is a dynamic evaluation that takes into account the kinetics of response to treatment and may help catch the real efficacy of an immunotherapy approach. We performed a retrospective monocentric study to explore the impact of TGR change after nivolumab administration as the second or later line of treatment in patients with metastatic renal cell carcinoma (RCC). We evaluated 27 patients, divided into three categories: Disease control (DC) if there was no PD; lower velocity PD (LvPD) if disease progressed but the TGR at second assessment (TGR2) was lower than the TGR at first assessment (TGR1); higher velocity PD (HvPD) if TGR2 was higher than TGR1. The median OS for the DC group was 11.0 months (95% CI 5.0–17.0) (reference) vs. (not reached) NR (95% CI NR-NR) for LvPD (HR 0.27; 95% CI 0.06–1.30; p 0.102) vs. NR (95% CI NR–NR) for HvPD (HR 0.23; 95% CI 0.06–0.88; p 0.032). There was no difference between LvPD and DC (HR 1.21; 95% CI 0.20–7.28; p 0.838). In patients with metastatic RCC, the second or later line of nivolumab treatment may lead to a deceleration in TGR resulting in an improved survival outcome similar to that observed in patients experiencing tumor regression. In this subgroup, especially in the presence of a clinical benefit, continuing the treatment beyond progression can be recommended.

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Tumor growth characteristics of the Walker 256 AR tumor, a regressive variant of the rat Walker 256 A tumor

Brazilian Archives of Biology and Technology ◽

10.1590/s1516-89132010000500014 ◽

2010 ◽

Vol 53 (5) ◽

pp. 1101-1108 ◽

Cited By ~ 2

Author(s):

Fernando Guimarães ◽

Alessandra Soares Schanoski ◽

Tereza Cristina Samico Cavalcanti ◽

Priscila Bianchi Juliano ◽

Ana Neuza Viera-Matos ◽

...

Keyword(s):

Growth Rate ◽

Tumor Growth ◽

Wistar Rats ◽

Tumor Regression ◽

Growth Characteristics ◽

Tumor Growth Rate ◽

Continuous Growth ◽

Tumor Bearing ◽

Walker 256 ◽

Complete Tumor

The present study aimed at characterizing the subcutaneous development of the Walker 256 (W256) AR tumor, a regressive variant of the rat W256 A tumor. Wistar rats were injected subcutaneously with 4x10(6) W256 A or W256 AR tumor cells. The development of tumors was evaluated daily by percutaneous measurements. None of the W256 A tumors (n=20) regressed, but 62% of the W256 AR tumor-bearing rats (n=21) underwent complete tumor regression within 35 days. Continuous growth of AR tumors was characterized by an increase of the tumor growth rate from day 12, which reached values above 1.0 g/day, and were significantly higher (p<0.05) than those of the regressive AR tumors. Immunosuppression by irradiation before subcutaneous injection of AR cells completely abrogated tumor regression and was associated with severe metastatic dissemination. Daily evaluation of the tumor growth rate enabled the discrimination, in advance, between continuously growing tumors and those that regressed later on.

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LB1598 The impact of tumor growth rate on survival of acral melanoma

Journal of Investigative Dermatology ◽

10.1016/j.jid.2018.06.137 ◽

2018 ◽

Vol 138 (9) ◽

pp. B22

Author(s):

J. Ohn ◽

G. Jo ◽

S. Cho ◽

J. Mun

Keyword(s):

Growth Rate ◽

Tumor Growth ◽

Tumor Growth Rate ◽

Acral Melanoma ◽

The Impact

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PERSONALITY AND CANCER: DIFFERENCES IN THE CLINICAL AND PSYCHOLOGICAL CHARACTERISTICS OF THE PATIENT'S PERSONALITY AT HIGH AND LOW RATES OF TUMOR GROWTH

Problems in oncology ◽

10.37469/0507-3758-2018-64-6-805-809 ◽

2018 ◽

Vol 64 (6) ◽

pp. 805-809

Author(s):

Anna Nikolaeva ◽

Yelena Vaknin ◽

Gennadiy Zharinov

Keyword(s):

Prostate Cancer ◽

Growth Rate ◽

Comparative Analysis ◽

Tumor Growth ◽

Traumatic Event ◽

Psychological Research ◽

Psychological Characteristics ◽

Tumor Growth Rate ◽

The Impact

In this paper are presented the results and comparative analysis of the clinical and psychological research for the patient's personality with prostate cancer with high and low growth rate of the tumor. It was revealed that the nature of the oncological process does not depend on the perception by the patients of the impact of a traumatic event, in which the disease acts. For patients with a high tumor growth rate, the most characteristic are pliability, credulity, subordination (r = 0,887, p

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245 Human TLR8 knock-in mice potentiate immunotherapy responses of MC38 syngeneic tumors

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0245 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A264-A264

Author(s):

Shanshan Qi ◽

Hongjuan Zhang ◽

Ruilin Sun ◽

Annie An ◽

Henry Li ◽

...

Keyword(s):

T Cells ◽

Tumor Growth ◽

Cancer Immunotherapy ◽

Tumor Regression ◽

Tumor Growth Rate ◽

Tumor Growth Inhibition ◽

List Type ◽

Rna Recognition ◽

Ethical Guidelines ◽

Ifn Γ

BackgroundToll-like receptors (TLRs) serve critical roles in mediating innate immune responses against many pathogens. However, they may also bind to endogenous ligands and lead to the pathogenesis of autoimmunity. Although TLR8 belongs to the same TLR family as TLR7, its role in inflammation and tumor progression is not yet fully understood due to the lack of suitable animal models. In humans, both TLR7 and TLR8 recognize single-stranded self-RNA, viral RNA, and synthetic small molecule agonists.1, 2 However, mouse Tlr8 is non-functional due to the absence of 5 amino acids necessary for RNA recognition. In order to create a mouse model with functional TLR8, we replaced exon 3 of mouse Tlr8 with human TLR8, therefore developing a hTLR8 knock-in (KI) model. Both heterozygous and homozygous hTLR8 KI mice are viable with inflammatory phenotypes, i.e. enlarged spleens and livers, and significantly higher IL-12 p40 levels under TLR8 agonist treatment. In this study, we evaluated the potential use of hTLR8 mice for cancer immunotherapy studies.MethodshTLR8 mice, together with naïve C57BL/6 mice, were inoculated with MC38 syngeneic tumor cells. Tumor bearing mice were grouped at a mean tumor volume of approximately 100 mm3 for treatment with PBS or 10 mg/kg anti-PD-1 (RMP1-14) antibody. At the efficacy endpoint, spleens and tumors were collected for flow cytometry profiling.ResultsAnti-PD-1 treatment of MC38 tumors in naïve C57BL/6 led to moderate tumor growth inhibition (TGI = 54%). Interestingly, anti-PD-1 treatment showed improved efficacy in hTLR8 mice (TGI = 79%), including 2/10 tumors with complete tumor regression. In comparison, non-treated MC38 tumor growth rate was slower in hTLR8 mice than in naïve mice. Anti-PD-1 treated hTLR8 mice also had significantly increased IFN-γ and TNF-a positive CD4+ T cells in the spleen, along with higher numbers of differentiated effector T cells. In addition, hTLR8 mice have activated dendritic cells and macrophages, acting as critical steps in initiation of the inflammatory process, with higher levels of pro-inflammatory cytokines, such as IL-6, IFN-γ, TNF-a, and IL-1β, which may promote Th1 priming and differentiation of T cells into IFN-γ or TNF-a producing cells.ConclusionshTLR8 mice offer a great tool to model cancer immunotherapy in an inflammatory/autoimmunity prone background. Moreover, hTLR8 mice can be effectively used to shift a ‘cold’ tumor phenotype to ‘hot’ tumors in a syngeneic setting.Ethics ApprovalAnimal experiments were conducted in accordance with animal welfare law, approved by local authorities, and in accordance with the ethical guidelines of CrownBio (Taicang).ReferencesKugelberg E. Making mice more human the TLR8 way. Nat Rev Immunol 2014;14:6.Guiducci C, Gong M, Cepika A-M, et al. RNA recognition by human TLR8 can lead to autoimmune inflammation. J Exp Med 2013;210:2903–2919.

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Body Composition Changes in Gastric Cancer Patients during Preoperative FLOT Therapy: Preliminary Results of an Italian Cohort Study

Nutrients ◽

10.3390/nu13030960 ◽

2021 ◽

Vol 13 (3) ◽

pp. 960

Author(s):

Emanuele Rinninella ◽

Antonia Strippoli ◽

Marco Cintoni ◽

Pauline Raoul ◽

Raffaella Vivolo ◽

...

Keyword(s):

Gastric Cancer ◽

Body Composition ◽

Tumor Regression ◽

Evaluation Criteria ◽

Tumor Regression Grade ◽

Skeletal Muscle Index ◽

Before And After ◽

Gastric Cancer Patients ◽

The Impact ◽

Composition Changes

Background: The impact of the new chemotherapy, fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) on body composition in gastric cancer (GC) patients remains unknown. We assessed body composition changes of GC patients receiving the FLOT regimen and their impact on treatment outcomes. Methods: Preoperative pre- and post-FLOT computed tomography (CT) scans of advanced GC patients were studied. Lumbar skeletal muscle index (SMI) and adipose indices were calculated before and after FLOT. Results: A total of 26 patients were identified between April 2019 and January 2020. Nineteen patients were sarcopenic at diagnosis. The mean BMI decreased (from 24.4 ± 3.7 to 22.6 ± 3.1; p < 0.0001) as well as the SMI (from 48.74 ± 9.76 to 46.52 ± 9.98; p = 0.009) and visceral adipose index (VAI) (from 49.04 ± 31.06 to 41.99 ± 23.91; p = 0.004) during preoperative FLOT therapy. BMI, SMI, and VAI variations were not associated with toxicity, Response Evaluation Criteria in Solid Tumors (RECIST), response, delay and completion of perioperative FLOT chemotherapy, and the execution of gastrectomy; a decrease of SMI ≥ 5% was associated with a higher Mandard tumor regression grade (p = 0.01). Conclusions: Almost three-quarters (73.1%) of GC patients were sarcopenic at diagnosis. Preoperative FLOT was associated with a further reduction in SMI, BMI, and VAI. These changes were not associated with short-term outcomes.

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Targeted Treatment of Experimental Spinal Cord Glioma With Dual Gene-Engineered Human Neural Stem Cells

Neurosurgery ◽

10.1227/neu.0000000000001174 ◽

2015 ◽

Vol 79 (3) ◽

pp. 481-491 ◽

Cited By ~ 11

Author(s):

Alexander E. Ropper ◽

Xiang Zeng ◽

Hariprakash Haragopal ◽

Jamie E. Anderson ◽

Zaid Aljuboori ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Growth Rate ◽

Neural Stem Cells ◽

Tumor Growth ◽

Rat Model ◽

Weight Bearing ◽

Tumor Growth Rate ◽

Intramedullary Spinal Cord ◽

Human Neural Stem Cells

Abstract BACKGROUND There are currently no satisfactory treatments or experimental models showing autonomic dysfunction for intramedullary spinal cord gliomas (ISCG). OBJECTIVE To develop a rat model of ISCG and investigate whether genetically engineered human neural stem cells (F3.hNSCs) could be developed into effective therapies for ISCG. METHODS Immunodeficient/Rowett Nude rats received C6 implantation of G55 human glioblastoma cells (10K/each). F3.hNSCs engineered to express either cytosine deaminase gene only (i.e., F3.CD) or dual genes of CD and thymidine kinase (i.e., F3.CD-TK) converted benign 5-fluorocytosine and ganciclovir into oncolytic 5-fluorouracil and ganciclovir-triphosphate, respectively. ISCG rats received injection of F3.CD-TK, F3.CD, or F3.CD-TK debris near the tumor epicenter 7 days after G55 seeding, followed with 5-FC (500 mg/kg/5 mL) and ganciclovir administrations (25 mg/kg/1 mL/day × 5/each repeat, intraperitoneal injection). Per humane standards for animals, loss of weight-bearing stepping in the hindlimb was used to determine post-tumor survival. Also evaluated were autonomic functions and tumor growth rate in vivo. RESULTS ISCG rats with F3.CD-TK treatment survived significantly longer (37.5 ± 4.78 days) than those receiving F3.CD (21.5 ± 1.75 days) or F3.CD-TK debris (19.3 ± 0.85 days; n = 4/group; P <.05, median rank test), with significantly improved autonomic function and reduced tumor growth rate. F3.DC-TK cells migrated diffusively into ISCG clusters to mediate oncolytic effect. CONCLUSION Dual gene-engineered human neural stem cell regimen markedly prolonged survival in a rat model that emulates somatomotor and autonomic dysfunctions of human cervical ISCG. F3.CD-TK may provide a novel approach to treating clinical ISCG.

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