The scope of the problem of primary tumor control

Cancer ◽  
1988 ◽  
Vol 61 (11) ◽  
pp. 2141-2147 ◽  
Author(s):  
Herman D. Suit
Keyword(s):  
Primary Tumor ◽  
Tumor Control

404: Immune Mediated Survival Advantage and Primary Tumor Control of Cryoablation Compared to Nephrectomy in a Murine Model of Advanced Renal Cancer

2006 ◽  
Vol 175 (4S) ◽  
pp. 132-132 ◽  
Author(s):  
Sean P. Hedican ◽  
Eric R. Wilkinson ◽  
Thomas F. Warner ◽  
Fred T. Lee ◽  
Stephen Y. Nakada
Keyword(s):  
Renal Cancer ◽  
Murine Model ◽  
Primary Tumor ◽  
Survival Advantage ◽  
Tumor Control ◽  
Advanced Renal Cancer ◽  
Immune Mediated

scholarly journals Apatinib Combined with Local Irradiation Leads to Systemic Tumor Control via Reversal of Immunosuppressive Tumor Microenvironment in Lung Cancer

2020 ◽  
Vol 52 (2) ◽  
pp. 406-418
Author(s):  
Li-jun Liang ◽  
Chen-xi Hu ◽  
Yi-xuan Wen ◽  
Xiao-wei Geng ◽  
Ting Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Primary Tumor ◽  
Tumor Control ◽  
Abscopal Effect ◽  
Antitumor Effects ◽  
Term Survival ◽  
Secondary Tumor ◽  
Immunosuppressive Tumor Microenvironment

PurposeThis study aimed to investigate the potential systemic antitumor effects of stereotactic ablative radiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor 2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma.Materials and MethodsLewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor; irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grew to the touchable size, mice were randomly divided into eight treatment groups. These groups received normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200 mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not to the primary tumor. The further tumor growth/regression of mice were followed and observed.ResultsFor the single 15 Gy modality, tumor growth delay could only be observed at the primary tumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primary and secondary tumor growth could be observed, indicated an abscopal effect was induced. Mechanism analysis suggested that programmed death-ligand 1 expression increased with SABR was counteract by additional apatinib therapy. Furthermore, when apatinib was combined with SABR, the composition of immune cells could be changed. More importantly, this two-pronged approach evoked tumor antigen–specific immune responses and the mice were resistant to another tumor rechallenge, finally, long-term survival was improved.ConclusionOur results suggested that the tumor microenvironment could be managed with apatinib, which was effective in eliciting an abscopal effect induced by SABR.

Thirty years' experience with Gamma Knife surgery for metastases to the brain

2009 ◽  
Vol 111 (3) ◽  
pp. 449-457 ◽  
Author(s):  
Bengt Karlsson ◽  
Patrick Hanssens ◽  
Robert Wolff ◽  
Michael Söderman ◽  
Christer Lindquist ◽  
...  
Keyword(s):  
Survival Time ◽  
Gamma Knife ◽  
Median Survival ◽  
Primary Tumor ◽  
Median Survival Time ◽  
Gamma Knife Surgery ◽  
Tumor Control ◽  
Primary Disease ◽  
Multiple Metastases ◽  
The Brain

Object The aim of this study was to analyze factors influencing survival time and patterns of distant recurrences after Gamma Knife surgery (GKS) for metastases to the brain. Methods Information was available for 1855 of 1921 patients who underwent GKS for single or multiple cerebral metastases at 4 different institutions during different time periods between 1975 and 2007. The total number of Gamma Knife treatments administered was 2448, an average of 1.32 treatments per patient. The median survival time was analyzed, related to patient and treatment parameters, and compared with published data following conventional fractionated whole-brain irradiation. Results Twenty-five patients survived for longer than 10 years after GKS, and 23 are still alive. Age and primary tumor control were strongly related to survival time. Patients with single metastases had a longer survival than those with multiple metastases, but there was no difference in survival between patients with single and multiple metastases who had controlled primary disease. There were no significant differences in median survival time between patients with 2, 3–4, 5–8, or > 8 metastases. The 5-year survival rate was 6% for the whole patient population, and 9% for patients with controlled primary disease. New hematogenous spread was a more significant problem than micrometastases in patients with longer survival. Conclusions Patient age and primary tumor control are more important factors in predicting median survival time than number of metastases to the brain. Long-term survivors are more common than previously assumed.

scholarly journals Overcoming resistance to STING agonist therapy to incite durable protective antitumor immunity

2020 ◽  
Vol 8 (2) ◽  
pp. e001182 ◽  
Author(s):  
Henrique Lemos ◽  
Rong Ou ◽  
Caroline McCardle ◽  
Yijun Lin ◽  
Jessica Calver ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Primary Tumor ◽  
Antitumor Immunity ◽  
Acquired Resistance ◽  
Tumor Control ◽  
Regulatory Pathways ◽  
Beneficial Effects ◽  
Immune Balance ◽  
Promote Tumor Growth ◽  
Inhibitor Drug

BackgroundActivating the Stimulator of Interferon Genes (STING) adaptor incites antitumor immunity against immunogenic tumors in mice, prompting clinical trials to test STING activators. However, STING signaling in the tumor microenvironment (TME) during development of Lewis lung carcinoma (LLC) suppresses antitumor immunity to promote tumor growth. We hypothesized that local immune balance favoring suppression of antitumor immunity also attenuates antitumor responses following STING activation. The purpose of this study was to evaluate how STING activation impacts antitumor responses in mice bearing LLC tumors.MethodsMice bearing established LLC tumors were treated with synthetic cyclic diadenyl monophosphate (CDA) to activate STING. Mice were monitored to assess LLC tumor growth, survival and protective antitumor immunity. Transcriptional and metabolic analyses were used to identify pathways responsive to CDA, and mice were co-treated with CDA and drugs that disrupt these pathways.ResultsCDA slowed LLC tumor growth but most CDA-treated mice (77%) succumbed to tumor growth. No evidence of tumor relapse was found in surviving CDA-treated mice at experimental end points but mice were not immune to LLC challenge. CDA induced rapid increase in immune regulatory pathways involving programmed death-1 (PD-1), indoleamine 2,3 dioxygenase (IDO) and cyclooxygenase-2 (COX2) in the TME. PD-1 blockade enhanced antitumor responses to CDA and increased mouse survival but mice did not eliminate primary tumor burdens. Two IDO inhibitor drugs had little or no beneficial effects on antitumor responses to CDA. A third IDO inhibitor drug synergized with CDA to enhance tumor control and survival but mice did not eliminate primary tumor burdens. In contrast, co-treatments with CDA and the COX2-selective inhibitor celecoxib controlled tumor growth, leading to uniform survival without relapse, and mice acquired resistance to LLC re-challenge and growth of distal tumors not exposed directly to CDA. Thus, mice co-treated with CDA and celecoxib acquired stable and systemic antitumor immunity.ConclusionsSTING activation incites potent antitumor responses and boosts local immune regulation to attenuate antitumor responses. Blocking STING-responsive regulatory pathways synergizes with CDA to enhance antitumor responses, particularly COX2 inhibition. Thus, therapy-induced resistance to STING may necessitate co-treatments to disrupt regulatory pathways responsive to STING in patients with cancer.

314: Equivalent Survival and Superior Primary Tumor Control of Cryoablation Relative to Radiofrequency Ablation in a Murine Model of Advanced Renal Cancer

2007 ◽  
Vol 177 (4S) ◽  
pp. 106-106
Author(s):  
Sean P. Hedican ◽  
Eric R. Wilkinson ◽  
Fred T. Lee ◽  
Thomas F. Warner ◽  
Stephen Y. Nakada
Keyword(s):  
Radiofrequency Ablation ◽  
Renal Cancer ◽  
Murine Model ◽  
Primary Tumor ◽  
Tumor Control ◽  
Advanced Renal Cancer

Prognostic factors and grading systems for overall survival in patients treated with radiosurgery for brain metastases: variation by primary site

2008 ◽  
Vol 109 (Supplement) ◽  
pp. 77-86 ◽  
Author(s):  
Daniel W. Golden ◽  
Kathleen R. Lamborn ◽  
Michael W. McDermott ◽  
Sandeep Kunwar ◽  
William M. Wara ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Brain Metastases ◽  
Primary Tumor ◽  
Tumor Control ◽  
Tumor Site ◽  
Newly Diagnosed ◽  
Primary Tumor Site ◽  
Grading Systems ◽  
Extracranial Metastases

Object The authors conducted a study to determine whether prognostic factors and the applicability of prognostic systems vary by primary tumor site in patients treated with radiosurgery for brain metastases. Methods The authors evaluated data obtained in patients who underwent radiosurgery with or without whole-brain radiotherapy (WBRT) from 1991 to 2005 for newly diagnosed brain metastases. Four groups were analyzed: 1) all primary sites combined, 2) breast, 3) lung, and 4) melanoma primary sites. Kaplan–Meier, log-rank, Cox proportional hazard uni- and multivariate analysis, and recursive partitioning analysis (RPA) were used to assess prognostic factors and 4 prognostic systems: Radiation Therapy Oncology Group (RTOG) RPA, Graded Prognostic Assessment (GPA), basic score for brain metastases (BSBM), and the newly proposed Golden grading system (GGS). The GGS divides patients into 4 prognostic groups by age ≥ 65 years, Karnofsky Performance Scale (KPS) score < 70, and known presence of extracranial metastases. Results Data acquired in 479 newly diagnosed patients with 1664 lesions were analyzed. The median survival time from diagnosis of brain metastases was 12.1 months; the median follow-up was 25.4 months in 73 patients who were censored. Survival and prognostic factors were equivalent for 369 patients treated with radiosurgery compared with 110 patients treated with radiosurgery and WBRT, so these subsets were combined. Multivariate analysis of all primary sites combined demonstrated age < 65 years, KPS score ≥ 70, no known extracranial metastases, and ≤ 3 brain metastases were associated with longer survival, and primary tumor control was not. In subgroup multivariate analysis of patients with breast, lung, or melanoma primaries, favorable factors included only primary tumor control in 87 patients with breast primary; age < 65 years, no known extracranial metastases, and ≤ 3 brain metastases in 169 patients with lung primary; and KPS ≥ 70 years, primary tumor control, and ≤ 3 brain metastases in 137 patients with melanoma primary. The median survival for ≤ 3 versus > 3 metastases was 15.6 and 16.9 months, respectively, for breast, 16.5 and 11.3 months for lung, and 9.0 and 5.7 months for melanoma. Analysis of the 4 prognostic systems (RTOG RPA, BSBM, GPA, and GGS) showed that each prognostic system's clinical applicability varied depending on primary tumor site. The RPA confirmed that GGS and primary tumor site are significant variables for prognosis. Conclusions Favorable prognostic factors for patients with newly diagnosed brain metastases treated with radiosurgery vary by primary site. The 4 prognostic grading systems analyzed were applicable to different primary sites depending on which prognostic factors each individual system incorporated. Therefore, the authors recommend further development and use of primary-specific prognostic systems.

Stereotactic radiosurgery using the Leksell Gamma Knife Perfexion unit in the management of patients with 10 or more brain metastases

2012 ◽  
Vol 117 (2) ◽  
pp. 237-245 ◽  
Author(s):  
Ramesh Grandhi ◽  
Douglas Kondziolka ◽  
David Panczykowski ◽  
Edward A. Monaco ◽  
Hideyuki Kano ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Gamma Knife ◽  
Median Survival ◽  
Primary Tumor ◽  
Systemic Disease ◽  
High Rate ◽  
Tumor Control ◽  
Karnofsky Performance Scale ◽  
Gamma Knife Perfexion

Object To better establish the role of stereotactic radiosurgery (SRS) in treating patients with 10 or more intracranial metastases, the authors assessed clinical outcomes and identified prognostic factors associated with survival and tumor control in patients who underwent radiosurgery using the Leksell Gamma Knife Perfexion (LGK PFX) unit. Methods The authors retrospectively reviewed data in all patients who had undergone LGK PFX surgery to treat 10 or more brain metastases in a single session at the University of Pittsburgh. Posttreatment imaging studies were used to assess tumor response, and patient records were reviewed for clinical follow-up data. All data were collected by a neurosurgeon who had not participated in patient care. Results Sixty-one patients with 10 or more brain metastases underwent SRS for the treatment of 806 tumors (mean 13.2 lesions). Seven patients (11.5%) had no previous therapy. Stereotactic radiosurgery was the sole prior treatment modality in 8 patients (13.1%), 22 (36.1%) underwent whole-brain radiation therapy (WBRT) only, and 16 (26.2%) had prior SRS and WBRT. The total treated tumor volume ranged from 0.14 to 40.21 cm3, and the median radiation dose to the tumor margin was 16 Gy. The median survival following SRS for 10 or more brain metastases was 4 months, with improved survival in patients with fewer than 14 brain metastases, a nonmelanomatous primary tumor, controlled systemic disease, a better Karnofsky Performance Scale score, and a lower recursive partitioning analysis (RPA) class. Prior cerebral treatment did not influence survival. The median survival for a patient with fewer than 14 brain metastases, a nonmelanomatous primary tumor, and controlled systemic disease was 21.0 months. Sustained local tumor control was achieved in 81% of patients. Prior WBRT predicted the development of new adverse radiation effects. Conclusions Stereotactic radiosurgery safely and effectively treats intracranial disease with a high rate of local control in patients with 10 or more brain metastases. In patients with fewer metastases, a nonmelanomatous primary lesion, controlled systemic disease, and a low RPA class, SRS may be most valuable. In selected patients, it can be considered as first-line treatment.

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