scholarly journals Genomic analysis reveals somatic mutations of ATM gene in DNA repair confer exceptional target lesion response to radiation therapy.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 130-130 ◽  
Author(s):  
Jason Joon Bock Lee ◽  
Andrew Jihoon Yang ◽  
Jee Suk Chang ◽  
Han Sang Kim ◽  
Hong In Yoon ◽  
...  
Keyword(s):  
Dna Repair ◽  
Radiation Therapy ◽  
Somatic Mutations ◽  
Response Rate ◽  
Chemotherapy Resistance ◽  
Genomic Analysis ◽  
Response Duration ◽  
Severe Toxicity ◽  
Therapeutic Implications ◽  
Brca 1

130 Background: Somatic mutations of genes involved in DNA repair (e.g. ATM and BRCA1/2) may result in chemotherapy resistance and poor prognosis, but may confer sensitivity to radiation therapy. In this study, we aimed to the hypothesis that patients with such mutations may be more susceptible to radiotherapy. Methods: Using prospectively collected RT registry, we identified patients who underwent both RT to gross disease and NGS panel screening between 2013 and 2019 (N = 27,664). From a cohort of 134 patients, 33 patients with somatic mutation in ATM or BRCA 1/2 were identified and closely matched with 33 patients without mutation using propensity score based on radiation dose and histology. Results: Infield response rate was evaluated in 66 patients with 90 gross lesions (ATM mutation, 11 patients and BRCA 1/2 mutation, 22 patients). The median tumor size and RT dose was 24 mm (3-140) and 40 Gy (12-66), respectively. Stark differences were seen in infield complete response rate, overall response rate, and local control rate at target lesions by ATM mutation (mutation vs. no mutation; 50% vs. 8%, 61% vs. 24%, and 94% vs. 58%, P < .05). Response duration was also longer ATM mutation (median 11 vs. 3 months, P = .001). However, RT-related toxicities were not different (17% vs. 11%, P = .515) and no severe toxicity occurred. Conclusions: ATM mutations confer exceptional responses to radiation therapy, even with palliative dose, which has potential therapeutic implications.

Cisplatin, doxorubicin, and 5-fluorouracil chemotherapy for salivary gland malignancies: a pilot study of the Northern California Oncology Group.

1987 ◽  
Vol 5 (6) ◽  
pp. 951-955 ◽  
Author(s):  
A P Venook ◽  
A Tseng ◽  
F J Meyers ◽  
I Silverberg ◽  
R Boles ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Salivary Gland ◽  
Overall Response Rate ◽  
Response Rate ◽  
Recurrent Disease ◽  
Response Duration ◽  
Complete Response ◽  
Outpatient Setting ◽  
Salivary Gland Cancer ◽  
Oncology Group

Seventeen patients with advanced or recurrent salivary gland cancer were treated with cisplatin, doxorubicin, and 5-fluorouracil combination chemotherapy (PAF). Two patients achieved a complete response and four patients achieved a partial response, for an overall response rate of 35%. Six of the nine patients who received PAF in the neoadjuvant setting did not respond and proceeded to surgery and/or radiation therapy. No difference in response rate was found between those patients treated for recurrent disease v those treated with neoadjuvant chemotherapy. All three patients with adenocarcinoma responded. The response duration in patients with metastatic or recurrent disease ranged from 6 to 15 months. The PAF regimen was delivered primarily in the outpatient setting and was associated with acceptable toxicity. PAF demonstrates activity in salivary gland malignancies, and further evaluation of this combination seems warranted.

scholarly journals Genomic Analysis of Exceptional Responders to Low-Dose Radiation Therapy Reveals Somatic Mutations in ATM

2016 ◽  
Vol 96 (2) ◽  
pp. S196
Author(s):  
J. Ma ◽  
J. Setton ◽  
P. Blecua Carrillo Albornoz ◽  
C.A. Barker ◽  
B.H. Lok ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Low Dose ◽  
Somatic Mutations ◽  
Genomic Analysis ◽  
Low Dose Radiation ◽  
Dose Radiation

Resistance against PSMA-targeting alpha-radiation therapy coincides with mutations in DNA-repair associated genes

2019 ◽  
Author(s):  
C Kratochwil ◽  
CP Heussel ◽  
F Bruchertseifer ◽  
U Haberkorn ◽  
A Morgenstern ◽  
...  
Keyword(s):  
Dna Repair ◽  
Radiation Therapy ◽  
Alpha Radiation

scholarly journals Inactivating Mutations of the IK Gene Weaken Ku80/Ku70-Mediated DNA Repair and Sensitize Endometrial Cancer to Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2487
Author(s):  
Chao Gao ◽  
Guangxu Jin ◽  
Elizabeth Forbes ◽  
Lingegowda S. Mangala ◽  
Yingmei Wang ◽  
...  
Keyword(s):  
Dna Repair ◽  
Endometrial Cancer ◽  
Protein Interactions ◽  
Somatic Mutations ◽  
The Cancer Genome Atlas ◽  
Response To Chemotherapy ◽  
Tcga Dataset ◽  
Inactivating Mutations

IK is a mitotic factor that promotes cell cycle progression. Our previous investigation of 271 endometrial cancer (EC) samples from the Cancer Genome Atlas (TCGA) dataset showed IK somatic mutations were enriched in a cluster of patients with high-grade and high-stage cancers, and this group had longer survival. This study provides insight into how IK somatic mutations contribute to EC pathophysiology. We analyzed the somatic mutational landscape of IK gene in 547 EC patients using expanded TCGA dataset. Co-immunoprecipitation and mass spectrometry were used to identify protein interactions. In vitro and in vivo experiments were used to evaluate IK’s role in EC. The patients with IK-inactivating mutations had longer survival during 10-year follow-up. Frameshift and stop-gain were common mutations and were associated with decreased IK expression. IK knockdown led to enrichment of G2/M phase cells, inactivation of DNA repair signaling mediated by heterodimerization of Ku80 and Ku70, and sensitization of EC cells to cisplatin treatment. IK/Ku80 mutations were accompanied by higher mutation rates and associated with significantly better overall survival. Inactivating mutations of IK gene and loss of IK protein expression were associated with weakened Ku80/Ku70-mediated DNA repair, increased mutation burden, and better response to chemotherapy in patients with EC.

The effect of eIF3a on anthracycline-based chemotherapy resistance by regulating DSB DNA repair

2021 ◽  
pp. 114616
Author(s):  
Juan Chen ◽  
Jun-Yan Liu ◽  
Zi-Zheng Dong ◽  
Ting Zou ◽  
Zhan Wang ◽  
...  
Keyword(s):  
Dna Repair ◽  
Chemotherapy Resistance

scholarly journals Development of an Objective Scoring System for Endoscopic Assessment of Radiation-Induced Upper Gastrointestinal Toxicity

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2136
Author(s):  
Daniel Lin ◽  
Shalini Moningi ◽  
Joseph Abi Jaoude ◽  
Ben S. Singh ◽  
Irina M. Cazacu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Radiation Therapy ◽  
Scoring System ◽  
Interobserver Agreement ◽  
Locally Advanced ◽  
Severe Toxicity ◽  
Cancer Trial ◽  
Gi Toxicity ◽  
Upper Gastrointestinal ◽  
Toxicity Scoring

We developed and implemented an objective toxicity scoring system to be used during endoscopic evaluation of the upper gastrointestinal (GI) tract in order to directly assess changes in toxicity during the radiation treatment of pancreatic cancer. We assessed and validated the upper GI toxicity of 19 locally advanced pancreatic cancer trial patients undergoing stereotactic body radiation therapy (SBRT). Wilcoxon-signed rank tests were used to compare pre- and post-SBRT scores. Comparison of the toxicity scores measured before and after SBRT revealed a mild increase in toxicity in the stomach and duodenum (p < 0.005), with no cases of severe toxicity observed. Kappa and AC1 statistics analysis were used to evaluate interobserver agreement. Our toxicity scoring system was reliable in determining GI toxicity with a good overall interobserver agreement for pre-treatment scores (stomach, κ = 0.71, p < 0.005; duodenum, κ = 0.88, p < 0.005) and post-treatment scores (stomach, κ = 0.71, p < 0.005; duodenum, κ = 0.76, p < 0.005). The AC1 statistics yielded similar results. With future usage, we hope this scoring system will be a useful tool for objectively and reliably assessing changes in GI toxicity during the treatment of pancreatic cancer and for GI toxicity assessments and comparisons during radiation therapy research trials.

Intraductal Tetracycline Therapy for the Treatment of Chronic Recurrent Parotitis

1994 ◽  
Vol 73 (4) ◽  
pp. 262-274 ◽  
Author(s):  
Lcdr David M. Bowling ◽  
Steven D. Rauch ◽  
Max L. Goodman
Keyword(s):  
Radiation Therapy ◽  
High Risk ◽  
Success Rate ◽  
Acute Inflammation ◽  
Double Blind ◽  
Cytotoxic Effects ◽  
Therapeutic Implications ◽  
Duct Ligation ◽  
Chronic Recurrent Parotitis ◽  
Histologic Changes

Chronic recurrent parotitis (CRP) is recurrent parotid inflammation with non-obstructive sialectasis. Therapies which produce acinar atrophy or remove the acini are effective in treating CRP. Parotidectomy, tympanic neurectomy, duct ligation, and radiation therapy have either a low success rate or a high risk of morbidity. Intraductal antibiotic instillation has been proposed as a possible method of treatment. We hypothesized that the cytotoxic effects of tetracycline could produce acinar atrophy. A double-blind experiment of intraductal tetracycline instillation was performed in ten rabbits. Acinar atrophy and acute inflammation were found in 40% of the tetracycline treated glands; controls had a complete absence of these histologic changes. These results support the use of tetracycline instillation to produce acinar atrophy and therefore, intraductal tetracycline may be an effective, low-risk therapy for CRP. The clinical features of CRP will be reviewed and therapeutic implications discussed.

Phase III Study of Intravenous Vinorelbine in Combination With Epirubicin Versus Epirubicin Alone in Patients With Advanced Breast Cancer: A Scandinavian Breast Group Trial (SBG9403)

2004 ◽  
Vol 22 (12) ◽  
pp. 2313-2320 ◽  
Author(s):  
Bent Ejlertsen ◽  
Henning T. Mouridsen ◽  
Sven T. Langkjer ◽  
Jorn Andersen ◽  
Johanna Sjöström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Complete Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Severe Toxicity ◽  
Free Survival

Purpose To determine whether the addition of intravenous (IV) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer. Patients and Methods A total of 387 patients were randomly assigned to receive IV epirubicin 90 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, or epirubicin 90 mg/m2 IV on day 1. Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity. In addition, epirubicin was discontinued at a cumulative dose of 1,000 mg/m2 (950 mg/m2 from June 1999). Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed. Reported results were all based on intent-to-treat analyses. Results Overall response rates to vinorelbine and epirubicin, and epirubicin alone, were 50% and 42%, respectively (P = .15). The complete response rate was significantly superior in the combination arm (17% v 10%; P = .048) as was median duration of progression-free survival (10.1 months v 8.2 months; P = .019). Median survival was similar in the two arms (19.1 months v 18.0 months; P = .50). Leukopenia related complications, stomatitis, and peripheral neuropathy were more common in the combination arm. The incidences of cardiotoxicity and constipation were similar in both arms. Conclusion Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival.

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