tumor shrinkage
Recently Published Documents


TOTAL DOCUMENTS

373
(FIVE YEARS 91)

H-INDEX

33
(FIVE YEARS 5)

2022 ◽  
Vol 11 ◽  
Author(s):  
Federica Recine ◽  
Alessandro De Vita ◽  
Valentina Fausti ◽  
Federica Pieri ◽  
Alberto Bongiovanni ◽  
...  

BackgroundNTRK (neurotrophic tyrosine receptor kinase)-rearranged spindle cell neoplasms are a new group of tumors included in the new 5th edition of the World Health Organization (WHO) classification of soft Tissue and Bone Sarcomas. These tumors are characterized by NTRK gene fusions and show a wide spectrum of histologies and clinical behavior. Several targeted therapies have recently been approved for tumors harboring NTRK fusions, including STS.Case PresentationA 26-year-old male with advanced, pretreated NTRK rearranged spindle cell neoplasm and liver, lung and bone metastases was treated with larotrectinib on a continuous 28-day schedule, at a dose of 100 mg twice daily. An 18FDG-PET/CT scan performed after 7 days of treatment showed tumor shrinkage in both visceral and bone lesions. There was no drug-related toxicity. Subsequent evaluations confirmed continued tumor regression in disease sites. The patient is well and continues treatment.ConclusionThe clinical and radiological response of our patient with an uncommon TPM4 (exon 7)-NTRK1 (exon 12) gene fusion tumor treated with a first-generation TRK inhibitor could contribute to a better understanding of the biology of this new STS entity and help to improve patient management.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Osman Öcal ◽  
Regina Schinner ◽  
Kerstin Schütte ◽  
Enrico N. de Toni ◽  
Christian Loewe ◽  
...  

Abstract Background The aim of this study was to explore the relationship between follow-up imaging characteristics and overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients under sorafenib treatment. Methods Associations between OS and objective response (OR) by mRECIST or early tumor shrinkage (ETS; ≥20% reduction in enhancing tumor diameter at the first follow-up imaging) were analyzed in HCC patients treated with sorafenib within a multicenter phase II trial (SORAMIC). 115 patients were included in this substudy. The relationship between survival and OR or ETS were explored. Landmark analyses were performed according to OR at fixed time points. Cox proportional hazards models with OR and ETS as a time-dependent covariate were used to compare survival with factors known to influence OS. Results The OR rate was 29.5%. Responders had significantly better OS than non-responders (median 30.3 vs. 11.4 months; HR, 0.38 [95% CI, 0.22–0.63], p < 0.001), and longer progression-free survival (PFS; median 10.1 vs. 4.3 months, p = 0.015). Patients with ETS ≥ 20% had longer OS (median 22.1 vs. 11.4 months, p = 0.002) and PFS (median 8.0 vs. 4.3 months, p = 0.034) than patients with ETS < 20%. Besides OR and ETS, male gender, lower bilirubin and ALBI grade were associated with improved OS in univariate analysis. Separate models of multivariable analysis confirmed OR and ETS as independent predictors of OS. Conclusion OR according to mRECIST and ETS in patients receiving sorafenib treatment are independent prognostic factors for OS. These parameters can be used for assessment of treatment benefit and optimal treatment sequencing in patients with advanced HCC.


Vestnik ◽  
2021 ◽  
pp. 291-295
Author(s):  
Ж.Ж. Жолдыбай ◽  
Г.И. Хуснутдинова ◽  
Ж.К. Жакенова ◽  
С.Е. Есентаева ◽  
А.Н. Ахмульдинова ◽  
...  

Определение изменений опухолевого роста является важной характеристикой клинической оценки терапии рака - как уменьшение размеров опухоли (объективный ответ), так и прогрессирование заболевания являются полезными конечными точками клинических исследований. Критерии RECIST были впервые опубликованы в 2000 г. и с тех пор начали применяться в мировой онкологической практике для оценки эффективности лечения. В 2009 году критерии RECIST 1.0 были пересмотрены и дополнены новыми данными RECIST 1.1 (2009 г.). Учитывая применение химиотаргетной терапии и особенности ответа на нее опухоли, предложены SACT критерии, модифицированные критерии RECIST (mRECIST) как способ адаптации критериев RECIST. Современные знания критериев оценки лечения солидных опухолей поможет лучевым диагностам правильно интерпретировать результаты исследований. В работе представлен обзор научных исследований по критериям оценки опухолевого ответа на лечение по данным радиологических исследований. Determining of tumor changes is an important characteristic of the clinical evaluation of cancer therapy - both tumor shrinkage (objective response) and disease progression are useful endpoints of clinical trials. The RECIST criteria were first published in 2000 and since then have been used in the global oncological practice to assess the effectiveness of treatment. In 2009, the RECIST 1.0 criteria were revised and supplemented with new data from RECIST 1.1 (2009). Taking into account the use of target chemotherapy and the peculiarities of the tumor response to it, the SACT criteria and modified RECIST criteria (mRECIST) are proposed as a way to adapt the RECIST criteria. Modern knowledge of the criteria for ASSESSMENT OF TUMOR RESPONSE will help radiologyst to correctly interpret the research results. The paper provides an overview of scientific studies on the criteria for evaluating tumor response to treatment based on radiological studies.


2021 ◽  
Vol 11 ◽  
Author(s):  
Huzaifa Piperdi ◽  
Daniella Portal ◽  
Shane S. Neibart ◽  
Ning J. Yue ◽  
Salma K. Jabbour ◽  
...  

Lung cancer treatment is constantly evolving due to technological advances in the delivery of radiation therapy. Adaptive radiation therapy (ART) allows for modification of a treatment plan with the goal of improving the dose distribution to the patient due to anatomic or physiologic deviations from the initial simulation. The implementation of ART for lung cancer is widely varied with limited consensus on who to adapt, when to adapt, how to adapt, and what the actual benefits of adaptation are. ART for lung cancer presents significant challenges due to the nature of the moving target, tumor shrinkage, and complex dose accumulation because of plan adaptation. This article presents an overview of the current state of the field in ART for lung cancer, specifically, probing topics of: patient selection for the greatest benefit from adaptation, models which predict who and when to adapt plans, best timing for plan adaptation, optimized workflows for implementing ART including alternatives to re-simulation, the best radiation techniques for ART including magnetic resonance guided treatment, algorithms and quality assurance, and challenges and techniques for dose reconstruction. To date, the clinical workflow burden of ART is one of the major reasons limiting its widespread acceptance. However, the growing body of evidence demonstrates overwhelming support for reduced toxicity while improving tumor dose coverage by adapting plans mid-treatment, but this is offset by the limited knowledge about tumor control. Progress made in predictive modeling of on-treatment tumor shrinkage and toxicity, optimizing the timing of adaptation of the plan during the course of treatment, creating optimal workflows to minimize staffing burden, and utilizing deformable image registration represent ways the field is moving toward a more uniform implementation of ART.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2277-2277
Author(s):  
William Casey Wilson ◽  
John O Richards ◽  
Gabriela Andrejeva ◽  
Benjamin J Capoccia ◽  
Robyn J Puro ◽  
...  

Abstract Upregulation of CD47, the "don't eat me" signal, on the surface of tumors to evade immune surveillance is a common escape mechanism utilized during hematological malignancy and solid tumor development, progression, and relapse. We recently reported that AO-176, a clinical stage humanized anti-CD47 IgG2 antibody, possesses differentiated characteristics such as preferential binding of tumor cells compared to normal cells, negligible binding to red blood cells, non-ADCC direct tumor killing and elicits immunogenic cell death and DAMP induction, all in addition to single-agent phagocytosis. In vivo, AO-176 has exhibited broad anti-tumor activity in preclinical xenograft models of multiple myeloma (MM), acute myeloid leukemia, T cell acute lymphoblastic leukemia, and Burkitt lymphoma. In this study, the anti-tumor activity of AO-176 in an expanded set of preclinical models of B cell neoplasms was evaluated. We assessed In vivo anti-tumor activity in a diffuse large B cell lymphoma (DLBCL) preclinical xenograft model by inoculating Toledo cells into NSG mice and treating once weekly with either 25 mg/kg AO-176 or human IgG2 isotype control. Treatment with AO-176 resulted in profound tumor shrinkage, achieved complete responses in 8/10 mice, and extended survival for all treated mice through the 46 day dosing period, compared to all isotype control treated tumors reaching endpoint by day 21. Having previously observed significant tumor shrinkage and extension of survival in subcutaneous xenograft models of MM, we sought to evaluate anti-tumor activity of AO-176 in an orthotopic model of MM. Luciferase expressing RPMI-8226 cells were inoculated via intratibial injection into NOD-SCID mice and treated with either 25 mg/kg of AO-176 or human IgG2 isotype control once weekly. AO-176-treated mice showed significant reductions of bioluminescence on study days 7, 21, 35, and 41, and serum paraprotein at study end. Evaluation of bone lesions by x-ray showed significantly reduced average bone lysis score in the AO-176 treatment group at study day 41. We then compared the anti-tumor activity of AO-176 against the second generation proteosome inhibitor carfilzomib in a myeloma xenograft model. AO-176 dosed at 25 mg/kg once weekly achieved 72% TGI, compared to 47% and 27% TGI for tumors treated with 5 mg/kg and 2.5 mg/kg carfilzomib at day 29 post treatment. To elucidate the pathways and processes that may be underpinning the anti-tumor activity of AO-176, we performed bulk RNA sequencing on AO-176 or isotype control-treated tumors harvested at multiple time points from a MM xenograft model we previously reported as exhibiting profound sensitivity to AO-176 in vivo. Murine transcripts from harvested tumor RNA were evaluated to assess differences in immune infiltrate resulting from AO-176 treatment. Days 3 and 7 post treatment with AO-176 showed the greatest number of differentially expressed genes compared to control treated tumors. The top enriched pathway on day 3 was microglia phagocytosis. Principal component analysis of gene expression indicated partitioning of day 3 post AO-176 treatment from the rest of the groups. Furthermore, deconvolution of abundances of infiltrating immune cells using CIBERSORT via TIMER analytical tool showed an enrichment of macrophages relative to other cell types on day 3 post treatment. To extend our RNA sequencing findings, we then sought to evaluate intratumoral immune cell populations after AO-176 treatment in a subcutaneous MM xenograft model. MM cells were inoculated into NOD-SCID mice, then treated with 25 mg/kg AO-176 or human IgG2 isotype control. At 48 hours post treatment, tumors were harvested, and we observed an increase of macrophages in the AO-176 treated tumors, confirming our previous results. In summary, the robust preclinical data in DLBCL and MM warrants further development of AO-176 for treatment of hematological malignancies. AO-176 is being evaluated in phase 1/2 clinical trials for the treatment of patients with solid tumors (NCT03834948) and with MM (NCT04445701). Disclosures Wilson: Arch Oncology: Current Employment. Richards: Arch Oncology: Current Employment. Andrejeva: Arch Oncology: Current Employment. Capoccia: Arch Oncology: Current Employment. Puro: Arch Oncology: Current Employment. Donio: Arch Oncology: Current Employment. Hiebsch: Arch Oncology: Current Employment. Kashyap: Arch Oncology: Current Employment. Pereira: Arch Oncology: Current Employment.


2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A457-A457
Author(s):  
Jermaine Coward ◽  
Sophia Frentzas ◽  
Anna Mislang ◽  
Bo Gao ◽  
Charlotte Lemech ◽  
...  

BackgroundPlatinum-resistant/refractory epithelial ovarian cancer (PROC) is a high unmet medical need with limited treatment options and a median survival of 12–15 months.1 Single agent PD-(L)1 inhibitors have objective response rates (ORR) of less than 10%.2 3 However, combination of nivolumab plus bevacizumab yields a higher ORR of 16.7% in platinum-resistant patients (pts), indicating synergistic activity between PD-1 inhibition and anti-angiogenic therapy in this disease.4 Here, we present initial efficacy and safety data for AK112, a bispecific antibody targeting PD-1 and VEGF-A, in pts with PROC.MethodsPts with PROC were enrolled in an ongoing Phase 1a/1b study of AK112 (NCT04047290). Tumor assessments based on RECIST v1.1 were performed once every 8 weeks/2 cycles for the first 12 months, and every 12 weeks thereafter.ResultsAs of 16 July 2021, 19 PROC pts, of which 6 had platinum-refractory disease, have received AK112 at doses ranging from 3 mg/kg to 30 mg/kg Q2W. Seventeen pts (89.5%) had ≥2 lines of prior therapy in the recurrent/metastatic setting and 7 pts (36.8%) had prior bevacizumab. Seventeen pts had at least 1 post-baseline tumor assessment. Median duration of follow-up was 4.5 months. ORR was 29.4% (5/17; 2 clear cell, 3 high-grade serous]). Among the 5 responders, 3 pts received 20mg/kg Q2W AK112 and 1 pt each had 3mg/kg and 10mg/kg Q2W AK112. Median duration of response was not reached. One pt, who had clear cell PROC and received prior immune checkpoint inhibitor (ICI) therapy, had tumor shrinkage of 70% and continued treatment for more than 17 months. Another pt, who had high-grade serous ovarian cancer and prior treatment with bevacizumab, had tumour shrinkage of 65% and continued treatment for more than 4 months. Disease control rate (DCR) was 76.5% (13/17), with tumor shrinkage observed in 11 pts (64.7%). Twelve out of 19 (63.2%) pts experienced treatment-related adverse events (TRAEs). Three pts (15.8%) experienced Grade 3 TRAEs (hypertension and transaminitis in 1 pt; and hypertension and colitis). There were no Grade 4–5 TRAEs. Commonly reported TRAEs were hypertension (15.8%), arthralgia (15.8%), fatigue (15.8%), hypothyroidism (10.5%) and rash (10.5%).ConclusionsThe initial results from Study AK112-101 demonstrate that AK112 garners an encouraging anti-tumor activity and a favorable safety profile in patients with platinum-resistant/refractory epithelial ovarian cancer. AK112 will be further evaluated for the treatment of platinum-resistant/refractory epithelial ovarian cancer in a Phase 2 study.AcknowledgementsAkeso Biopharma, Inc would like to thank the patients, investigators and site staff for their participation in this study.Trial RegistrationClinicalTrials.gov Identifier: NCT04047290ReferencesPujade-Lauraine E, Banerjee S, Pignata S. Management of platinum-resistant, relapsed epithelial ovarian cancer and new drug perspectives. J Clin Oncol 2019; 37:2437–2448.Disis ML, Taylor MH, Kelly K, et al. Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer: Phase 1b Results From the JAVELIN Solid Tumor Trial. JAMA Oncol 2019; 5:393–401.Matulonis UA, Shapira-Frommer RS, Santin A, et al. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: Interim results from the phase 2 KEYNOTE-100 study. J Clin Oncol 2018; 36: suppl abstr 5511.Liu JF, Herold C, Gray KP, et al. Assessment of Combined Nivolumab and Bevacizumab in Relapsed Ovarian Cancer: A Phase 2 Clinical Trial. JAMA Oncol 2019;5:1731–1738.Ethics ApprovalThis study received ethics approval from Bellberry Human Research Ethics Committee (HREC) on 05 Nov 2019 (Application number 2019-05-459-AB). In accordance with ICH Good Clinical Practice Guidelines and the Declaration of Helsinki, study participants gave informed consent voluntarily before participating in this study.


Author(s):  
Monica R Gadelha ◽  
Luiz Eduardo Wildemberg ◽  
Leandro Kasuki

Abstract Currently, first-generation somatostatin receptor ligands (fg-SRLs), octreotide LAR and lanreotide autogel, are the mainstays of acromegaly treatment and achieve biochemical control in approximately 40% of patients and tumor shrinkage in over 60% of patients. Pasireotide, a second-generation SRL, shows higher efficacy with respect to both biochemical control and tumor shrinkage but has a worse safety profile. In this review, we discuss the future perspectives of currently available SRLs, focusing on the use of biomarkers of response and precision medicine, new formulations of these SRLs and new drugs, which are under development. Precision medicine, which is based on biomarkers of response to treatment, will help guide the decision-making process by allowing physicians to choose the appropriate drug for each patient and improving response rates. New formulations of available SRLs, such as oral, subcutaneous depot and nasal octreotide, may improve patients’ adherence to treatment and quality of life since there will be more options available that better suit each patient. Finally, new drugs, such as paltusotine, somatropin, ONO-5788 and ONO-ST-468, may improve treatment adherence and present higher efficacy than currently available drugs.


PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257551
Author(s):  
Masashi Ishikawa ◽  
Atsuo Takashima ◽  
Yusuke Nagata ◽  
Ryoichi Sawada ◽  
Masahiko Aoki ◽  
...  

Background In clinical practice, the same chemotherapeutic agents are occasionally reused (re-challenge) after failure of all available standard chemotherapy options for metastatic colorectal cancer (mCRC). However, the benefits of re-challenge chemotherapy (Re-Cx) are unclear. This retrospective study evaluated the efficacy of Re-Cx, focusing on the tumor growth rate (TGR). Methods The study included mCRC patients with measurable lesions who received Re-Cx from November 2011 to October 2018 at National Cancer Center Hospital. Re-Cx was defined as re-administration of agents which had been used in prior lines of chemotherapy and discontinued due to disease progression. We compared the TGR immediately after initiating Re-Cx regimens with that observed at the time of disease progression during prior chemotherapy (Prior-Cx) immediately before Re-Cx. Results Of the 25 patients who received Re-Cx, five patients received two Re-Cx regimens. Therefore, a total of 30 cases of Re-Cx were analyzed in this study. The regimens of Re-Cx were oxaliplatin based (19 cases), irinotecan based (8 cases), and others (3 cases). Although the objective response rate to Re-Cx was 0%, the disease control rate was 60% (18 cases), and 40% (12 cases) showed some tumor shrinkage. We compared the effects of Re-Cx and Prior-Cx by the TGR and found that the TGR of Re-Cx was slower than that recorded in Prior-Cx in 26 of 30 cases (87%). In particular, the ratio of% TGR <0, which indicates tumor shrinkage, was obtained in 13 of 30 cases (43.3%). The median progression-free survival and overall survival after Re-Cx were 3.8 and 6.57 months, respectively. Conclusion We found that Re-Cx may have some anti-tumor efficacy as salvage treatment for mCRC and these results also suggested the clinical benefits of Re-Cx.


Immunotherapy ◽  
2021 ◽  
Author(s):  
Yuchen Yang ◽  
Lingyan Xu ◽  
Danping Wang ◽  
Bingqing Hui ◽  
Xiaofei Li ◽  
...  

There exists a dilemma in the treatment of microsatellite stability (MSS) metastatic colorectal cancer (mCRC) owing to limited therapeutic options. Based on the promising results of the REGONIVO trial, combination of anti-PD-1 and regorafenib could be applicable for this kind of patients. Here we first report a case of an MSS mCRC patient who received sinitilimab plus regorafenib as third-line treatment and suffered severe multisystem treatment-related adverse events including Grade 3 myocarditis, myositis, myasthenia gravis, dermatitis, hepatitis, etc. Fortunately, all these adverse events have been reversed with administration of corticosteroids. Though evidence of tumor shrinkage was not found, CEA levels markedly decreased. Therefore, anti-PD-1 plus regorafenib might be optional for the MSS mCRC patients which requires special caution in the clinical practice.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaojuan Yang ◽  
Xinghong Xian ◽  
Yongsheng Wang ◽  
Meng Qiu

Abstract Background The prognostic potential of early tumor shrinkage (ETS) and depth of response (DpR) in pancreatic cancer (PC) is unclear. Here, we recruited 90 patients with recurrent and metastatic PC (RMPC) who had received chemotherapy as first-line therapy to assess the prognostic potential of these markers. Methods ETS is characterized as a ≥ 20% depletion in the sum-of-the-longest-diameters (SLD) of measurable tumor lesions at 6–12 weeks than the baseline. DpR is the maximum shrinkage (%) from the baseline to nadir. We evaluated corrections in ETS and DpR with survival. Results Of the 63 patients in which ETS assessment was possible, 21 (33.3%) achieved ETS. We found a significant association between the incidence of ETS and an improved rate of progression-free survival (PFS; 6.5 vs. 2.2 months; p < 0.001) and overall survival (OS; 12.1 vs. 6.0 months; p = 0.014). The median value of DpR was − 23.66%. DpR was also related to improved PFS (9.3 vs. 3.1 months; p < 0.001) and OS (18.2 vs. 7.3 months; p < 0.001). Patients who had distant metastasis, not local recurrence, with ETS showed markedly better outcomes. In a multivariate model, both ETS and DpR were independent predictors of OS in the whole population. Conclusions ETS and DpR may predict favorable outcomes for RMPC patients who had received chemotherapy as first-line therapy, independent of the agents used. Further studies on the exploratory analyses of the optimum ETS cut-off value in recurrent PC patients to predict favorable clinical outcomes are required.


Sign in / Sign up

Export Citation Format

Share Document