Intratumoral Therapy I: Association of Immunotherapy with Permanent Long Term Cure of Metastatic Cancer

2018 ◽  
Vol 07 (04) ◽  
Author(s):  
Max Cohen ◽  
Alfred Ketcham ◽  
Ronald Herberman
Keyword(s):  
Metastatic Cancer ◽  
Intratumoral Therapy

scholarly journals An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marisa Nacke ◽  
Emma Sandilands ◽  
Konstantina Nikolatou ◽  
Álvaro Román-Fernández ◽  
Susan Mason ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Cellular Responses ◽  
Signalling Pathways ◽  
External Signal ◽  
Phosphoinositide Metabolism ◽  
Invasion And Metastasis ◽  
3 Dimensional

AbstractThe signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive cellular responses occur is unclear. Here, we report development of 3-Dimensional culture analyses to separately quantify growth and invasion. We identify that alternate variants of IQSEC1, an ARF GTPase Exchange Factor, act as switches to promote invasion over growth by controlling phosphoinositide metabolism. All IQSEC1 variants activate ARF5- and ARF6-dependent PIP5-kinase to promote PI(3,4,5)P3-AKT signalling and growth. In contrast, select pro-invasive IQSEC1 variants promote PI(3,4,5)P3 production to form invasion-driving protrusions. Inhibition of IQSEC1 attenuates invasion in vitro and metastasis in vivo. Induction of pro-invasive IQSEC1 variants and elevated IQSEC1 expression occurs in a number of tumour types and is associated with higher-grade metastatic cancer, activation of PI(3,4,5)P3 signalling, and predicts long-term poor outcome across multiple cancers. IQSEC1-regulated phosphoinositide metabolism therefore is a switch to induce invasion over growth in response to the same external signal. Targeting IQSEC1 as the central regulator of this switch may represent a therapeutic vulnerability to stop metastasis.

scholarly journals Incident Type 2 Diabetes Risk of Selective Estrogen Receptor Modulators in Female Patients with Breast Cancer

2021 ◽  
Vol 14 (9) ◽  
pp. 925
Author(s):  
Yeo-Jin Choi ◽  
Keunhyeong Bak ◽  
Yoon Yeo ◽  
Yongwon Choi ◽  
Sooyoung Shin
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Cancer ◽  
Selective Estrogen Receptor Modulators ◽  
Diabetes Risk ◽  
Incident Diabetes ◽  
Estrogen Receptor Modulators ◽  
Increase Diabetes Risk ◽  
Receptor Modulators

Accumulating evidence indicates a link between diabetes and cancer. Selective estrogen receptor modulators (SERMs) may increase diabetes risk via antiestrogen effects. This study investigated incident diabetes risk of SERM treatment and its effects on metastatic cancer and death prevention in breast cancer survivors. This retrospective cohort study included female patients with early-stage breast cancer, treated with or without SERMs, between 2008 and 2020 in a tertiary care hospital in Korea. Four propensity score-matched comparison pairs were designed: SERM use versus non-use, long-term use (≥1500 days) versus non-use, tamoxifen use versus non-use, and toremifene use versus non-use; then, logistic regression analysis was performed for risk analysis. SERMs in general were not associated with an elevated risk of diabetes; however, when used for ≥1500 days, SERMs—especially toremifene—substantially increased diabetes risk in breast cancer patients (OR 1.63, p = 0.048). Meanwhile, long-term SERM treatment was effective at preventing metastatic cancer (OR 0.20, p < 0.001) and death (OR 0.13, p < 0.001). SERM treatment, albeit generally safe and effective, may increase diabetes risk with its long-term use in women with breast cancer. Further studies are required to verify the association between toremifene treatment and incident diabetes.

The clinical significance of oophorectomy in gastric patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15646-e15646
Author(s):  
H. Song ◽  
J. Kim ◽  
Y. Do ◽  
W. Lee ◽  
S. Ryu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Time ◽  
Cancer Patients ◽  
Gastric Resection ◽  
Metastatic Cancer ◽  
Survival Duration ◽  
Term Survival ◽  
Recurrent Cancer ◽  
Gastric Cancer Patients

e15646 Background: The oophorectomy in isolated metastasis of ovary can lead to long term survival in patients with gastric cancer, but the clinical significance of oophorectomy in stage IV gastric cancer patients is not known well in this time. Methods: We reviewed the medical record of the 55 gastric cancer patients who were metastasis or recurrent in ovary at Dongsan Medical Center, Kimyung University School of Medicine, Daegu, Korea from 1985 to 2008. Results: Twenty-one patients were metastasis to ovary at the time of diagnosis of gastric cancer, and 34 patients were recurrent in ovary after the gastric resection. The mean age was 45.3 ± 11.6 years in metastatic cancer and 46.8 ±12.6 years in recurrent cancer patients. The stage at the time of gastric resection in 34 recurrent patients were I in 3, II in 1, III in 18, and IV in 10. Adjuvant chemotherapy were performed in 26 (76.5%) patients. Oophorectomy were performed in 33 (97.1%) of recurrent cancer, and 17 (81.0%) of metastatic cancer. The 1-year and 2-year survival rate of metastatic cancer were 14.7%, and 0%, and 1-year, 2-year, and 3-year survival rate of recurrent cancer were 47.2%, 18.1%, and 0%, respectively. The median survival duration of metastatic cancer were 8.9 ±1.0 months, and recurrent cancer were 11.4 ±2.3 months. Recurrent cancer were better survival than metastatic cancer patients (p=0.014). The long-term survival (over 2 years) was noted in 5 patients of recurrent cancer patients. The stage of gastric cancer was correlated to overall survival time in total patients (p=0.028). But, the relapse-free survival time after gastrectomy is the only factor to predict survival duration after oophorectomy in recurrent cancer patients (p=0.029). Age, stage of gastric cancer, extent of involvement of ovary, and systemic chemotherapy were not related to survival time of recurrent cancer patients. Conclusions: The survival time in patients with oophorectomy in recurrent gastric cancer was correlated to relapse-free survival time after gastric resection. No significant financial relationships to disclose.

Hypothyroidism and Thyroid Autoimmunity as a Prognostic Biomarker of Better Response in Metastatic Cancer Long-Term Survivors Treated with Sunitinib

Thyroid ◽  
2016 ◽  
Vol 26 (9) ◽  
pp. 1336-1337 ◽  
Author(s):  
Fabiana Pani ◽  
Francesco Atzori ◽  
Germana Baghino ◽  
Francesco Boi ◽  
Maria Teresa Ionta ◽  
...  
Keyword(s):  
Prognostic Biomarker ◽  
Metastatic Cancer ◽  
Thyroid Autoimmunity ◽  
Long Term Survivors

Resection of Single Metachronous Liver Metastases from Breast Cancer Stage I-II Yield Excellent Overall and Disease-Free Survival. Single Center Experience and Review of the Literature

2015 ◽  
Vol 32 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Céline Vertriest ◽  
Giammauro Berardi ◽  
Federico Tomassini ◽  
Rudy Vanden Broucke ◽  
Herman Depypere ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liver Metastases ◽  
Metastatic Cancer ◽  
Disease Free Survival ◽  
Stage I ◽  
Review Of The Literature ◽  
Term Survival ◽  
Free Survival ◽  
Disease Free

Purpose: Improved survival after liver resection for breast cancer liver metastases (BCLM) has been proven; however, there is still controversy on predictive factors influencing outcomes. The analysis of factors related to primary and metastatic cancer eventually influencing long-term outcomes and a review of the literature are presented in this report. Methods: Twenty-seven patients diagnosed with metachronous BCLM between 1996 and 2013 were retrospectively reviewed. Patients who had a minimum disease-free interval between primary tumor and liver metastasis of 12 months, no more than 3 liver lesions, no macroscopic extra-hepatic disease and in which systemic therapy showed a good response were included. Results: Twenty-two patients (82%) were initially diagnosed with a stage I-II disease. Twelve patients presented with multiple liver metastases. The 5 years overall survival (OS) rate was 78%, while the 5 years disease-free survival (DFS) rate was 36%. Initial tumor stage III-IV at first diagnosis and number of metastases >1 was significantly associated with a shorter DFS at multivariate analysis (p = 0.03 and p = 0.04 respectively). Patients with multiple lesions had a median DFS of 15 months compared to 47 months in patients with a single lesion (p = 0.03). Conclusions: Resection of single BCLM from primary stage I-II cancer offers very good long-term survival rates and a low morbidity.

Molecular profiling of cancer outliers.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13025-e13025 ◽  
Author(s):  
Kyungsuk Jung ◽  
Marijo Bilusic ◽  
Jianming Pei ◽  
Michael Slifker ◽  
Yan Zhou ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Complete Response ◽  
Genetic Alterations ◽  
Cancer Center ◽  
Tumor Type ◽  
Tumor Tissues ◽  
Underlying Mechanisms ◽  
Genetic Profiles ◽  
Long Term Survivors

e13025 Background: A few patients with metastatic cancer survive exceptionally longer than others under the same treatment. We hypothesized that there is a specific biologic signature in genetic profiles of long-term survivors that plays a key role in sensitivity to systemic treatment. Methods: Twenty-six patients with metastatic cancer treated at Fox Chase cancer center with exceptional response were included in the study. Exceptional response was defined as complete response > 1 year or stable disease/partial response > 2 years at any time during the disease course. Archived tumor specimens of 16 patients were sequenced and analyzed using Ambry Genetics 142 gene panel. In addition, genes expressions in tumor tissues from 23 exceptional responders and 23 matched controls (age, sex and tumor type) were analyzed using two NanoString nCounter PanCancer panels (Pathway and Immune Profiling). Results: See Table. Conclusions: Multiple common mutations of NOTCH2, NF1, FANCD2, PIK3CB and EPHA5 were found in tumors that responded exceptionally well to treatments. Additionally, certain genes were significantly over-expressed or under-expressed in these tumors compared to matched controls. Underlying mechanisms that these genetic alterations foster, leading to susceptibility to treatment and prolonged patient survival, should be further studied. [Table: see text]

Hospital and Physician Volume or Specialization and Outcomes in Cancer Treatment: Importance in Quality of Cancer Care

2000 ◽  
Vol 18 (11) ◽  
pp. 2327-2340 ◽  
Author(s):  
Bruce E. Hillner ◽  
Thomas J. Smith ◽  
Christopher E. Desch
Keyword(s):  
Cancer Treatment ◽  
Cancer Care ◽  
Hospital Volume ◽  
Metastatic Cancer ◽  
Long Term Outcomes ◽  
Initial Surgery ◽  
Outcome Relationship ◽  
Initial Care ◽  
Volume Outcome

PURPOSE: To conduct a comprehensive review of the health services literature to search for evidence that hospital or physician volume or specialty affects the outcome of cancer care. METHODS: We reviewed the 1988 to 1999 MEDLINE literature that considered the hypothesis that higher volume or specialization equals better outcome in processes or outcomes of cancer treatments. RESULTS: An extensive, consistent literature that supported a volume-outcome relationship was found for cancers treated with technologically complex surgical procedures, eg, most intra-abdominal and lung cancers. These studies predominantly measured in-hospital or 30-day mortality and used the hospital as the unit of analysis. For cancer primarily treated with low-risk surgery, there were fewer studies. An association with hospital and surgeon volume in colon cancer varied with the volume threshold. For breast cancer, British studies found that physician specialty and volume were associated with improved long-term outcomes, and the single American report showed an association between hospital volume of initial surgery and better 5-year survival. Studies of nonsurgical cancers, principally lymphomas and testicular cancer, were few but consistently showed better long-term outcomes associated with larger hospital volume or specialty focus. Studies in recurrent or metastatic cancer were absent. Across studies, the absolute benefit from care at high-volume centers exceeds the benefit from break-through treatments. CONCLUSION: Although these reports are all retrospective, rely on registries with dated data, rarely have predefined hypotheses, and may have publication and self-interest biases, most support a positive volume-outcome relationship in initial cancer treatment. Given the public fear of cancer, its well-defined first identification, and the tumor-node-metastasis taxonomy, actual cancer care should and can be prospectively measured, assessed, and benchmarked. The literature suggests that, for all forms of cancer, efforts to concentrate its initial care would be appropriate.

scholarly journals Radiation for Oligometastatic Lung Cancer in the Era of Immunotherapy: What Do We (Need to) Know?

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2132
Author(s):  
Stephanie T. H. Peeters ◽  
Evert J. Van Limbergen ◽  
Lizza E. L. Hendriks ◽  
Dirk De Ruysscher
Keyword(s):  
Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Metastatic Cancer ◽  
Combined Treatment ◽  
Progression Free Survival ◽  
Phase Ii Trials ◽  
Consensus Definition ◽  
Term Survival ◽  
Oligometastatic Disease

Oligometastatic cancer is recognized as a separate entity within the spectrum of metastatic disease. It was suggested that patients with oligometastatic disease can obtain long-term survival by giving local ablative therapy (LAT) to all visible disease locations. However, the true extent from which metastatic cancer should be called “oligometastatic” is unknown, although a consensus definition for oligometastatic disease is proposed by research organizations, such as the EORTC (maximum of five metastases in three organs). Different states of the oligometastatic disease are defined, such as synchronous vs. metachronous, oligopersistent vs. oligoprogressive disease. All clinical trials including patients with non-small cell lung cancer (NSCLC) are small and most are not randomized. Two small randomized phase II trials on synchronous disease showed an improvement in progression free survival, with the addition of LAT, and one also demonstrated an overall survival benefit. Immune checkpoint inhibitors (ICI) were not part of the treatment in these trials, while ICI significantly improved long-term outcomes of patients with metastatic NSCLC. Radiotherapy might improve the prognosis of patients treated with ICI because of its immunostimulatory effects and the possibility to eradicate metastatic deposits. Here, we summarize the data for adding ablative radiotherapy to the treatment of oligometastatic NSCLC, especially in the ICI era, and discuss the challenges of combined treatment.

scholarly journals Anti-tumor response induced by immunologically modified carbon nanotubes and laser irradiation using rat mammary tumor model

2015 ◽  
Vol 08 (04) ◽  
pp. 1550036 ◽  
Author(s):  
Joseph T. Acquaviva ◽  
Cody F. Bahavar ◽  
Feifan Zhou ◽  
Xiaosong Li ◽  
Eric W. Howard ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Treatment Group ◽  
Laser Irradiation ◽  
Tumor Response ◽  
Metastatic Cancer ◽  
Local Treatment ◽  
Photothermal Effect ◽  
Term Survival ◽  
Primary Tumors

The ideal treatment modality for metastatic cancer would be a local treatment that can destroy primary tumors while inducing an effective systemic anti-tumor response. To this end, we developed laser immunotherapy, combining photothermal laser application with an immunoadjuvant for the treatment of metastatic cancer. Additionally, to enhance the selective photothermal effect, we integrated light-absorbing nanomaterials into this innovative treatment. Specifically, we developed an immunologically modified carbon nanotube combining single-walled carbon nanotubes (SWNTs) with the immunoadjuvant glycated chitosan (GC). To determine the effectiveness of laser irradiation, a series of experiments were performed using two different irradiation durations — 5 and 10 min. Rats were inoculated with DMBA-4 cancer cells, a metastatic cancer cell line. The treatment group of rats receiving laser irradiation for 10 min had a 50% long-term survival rate without residual primary or metastatic tumors. The treatment group of rats receiving laser irradiation for 5 min had no long-term survivors; all rats died with multiple metastases at several distant sites. Therefore, Laser+SWNT–GC treatment with 10 min of laser irradiation proved to be effective at reducing tumor size and inducing long-term anti-tumor immunity.

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