Clinical effects in a cohort of cancer patients overexposed during external beam pelvic radiotherapy.
AffiliationPan American Health Organization, Washington, DC, USA. firstname.lastname@example.org
MetadataShow full item record
AbstractPURPOSE: To evaluate the clinical outcome of 28 overexposed cancer patients in a cohort of 153 treated with pelvic irradiation and to correlate the outcome with the doses received. METHODS AND MATERIALS: Between August 2000 and March 2001, 153 patients were treated at the Instituto Oncológico Nacional of Panama with radiotherapy for cancers of the cervix, uterus, endometrium, prostate, and rectum using conventional techniques. In 56 patients, irradiated with partially blocked teletherapy fields, the treatment times were determined using a treatment planning system that generated isodose distributions. The absorbed doses received by the patients were calculated and the biologically effective doses (BEDs) and 2-Gy equivalent doses derived. The clinical outcome was evaluated using the Radiation Therapy Oncology Group (RTOG) and late effects on normal tissues-subjective, objective, management, analytic scales (LENT/SOMA). The relationships between clinical outcome and dose were investigated and compared with published data. RESULTS: Of the 56 patients for whom treatment times were generated with the treatment planning system, 28 received some doses per fraction approximately double those prescribed. Using an alpha/beta = 10 Gy, the tumor BED(10) values ranged from 77 to 225 Gy. The rest of the patients received doses within 10% of the prescribed values. Seventeen of the 28 overexposed patients died 35 days to 21 months after treatment; 13 of the fatalities were caused by rectal complications. Survival was longer in those patients who had undergone colostomy. Bladder complications were less enhanced. The nonoverexposed patients with cervical cancer exhibited a greater incidence of treatment failures than generally reported in other centers. CONCLUSION: This study provides the clinical outcome after high doses of pelvic radiotherapy in a range not previously well documented. For cervical cancer patients receiving both tele- and brachytherapy, some deaths in this overexposure cohort occurred from assumed consequential rectal injury within 2 years, when the BED(10) values exceeded 70-80 Gy. The incidence was asymptotic to 100% fatalities at >150 Gy. This confirmed and extended other data in the literature.
CitationClinical effects in a cohort of cancer patients overexposed during external beam pelvic radiotherapy. 2004, 59 (2):538-50 Int. J. Radiat. Oncol. Biol. Phys.
JournalInternational Journal of Radiation Oncology, Biology, Physics
- Biologically effective doses in medium dose rate brachytherapy of cancer of the cervix.
- Authors: Leborgne F, Fowler JF, Leborgne JH, Zubizarreta E, Chappell R
- Issue date: 1997
- Radiotherapy doses at special reference points correlate with the outcome of cervical cancer therapy.
- Authors: Yoshimura R, Hayashi K, Ayukawa F, Toda K, Iwata M, Oota S, Hoshi A, Wakatsuki M, Kurosaki H, Okazaki A, Shibuya H
- Issue date: 2008 Jul-Sep
- Evaluation of morbidity after external radiotherapy and intracavitary brachytherapy in 771 patients with carcinoma of the uterine cervix or endometrium.
- Authors: Yalman D, Arican A, Ozsaran Z, Celik OK, Yürüt V, Esassolak M, Haydaroglu A
- Issue date: 2002
- Comparative study of reference points by dosimetric analyses for late complications after uniform external radiotherapy and high-dose-rate brachytherapy for cervical cancer.
- Authors: Chen SW, Liang JA, Yeh LS, Yang SN, Shiau AC, Lin FJ
- Issue date: 2004 Oct 1
- Acute genitourinary toxicity after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity.
- Authors: Akimoto T, Ito K, Saitoh J, Noda SE, Harashima K, Sakurai H, Nakayama Y, Yamamoto T, Suzuki K, Nakano T, Niibe H
- Issue date: 2005 Oct 1
Showing items related by title, author, creator and subject.
AZD8186 study 1: phase I study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumour activity of AZD8186 in patients with advanced castration-resistant prostate cancer (CRPC), squamous non-small cell lung cancer, triple negative breast cancer and with PTEN-deficient/mutated or PIK3CB mutated/amplified malignancies, as monotherapy and in combination with vistusertib (AZD2014) or abiraterone acetate.Lillian, S; De Bono, J; Higano, C; Shapiro, G; Brugger, W; Mitchell, P; Colebrook, S; Klinowska, T; Barry, S; Dean, Emma J; et al. (2016-12)
Mitochondrial oxidative stress in cancer-associated fibroblasts drives lactate production, promoting breast cancer tumor growth: understanding the aging and cancer connection.Balliet, R M; Capparelli, C; Guido, C; Pestell, T G; Martinez-Outschoorn, U E; Lin, Z; Whitaker-Menezes, D; Chiavarina, B; Pestell, R G; Howell, Anthony; et al. (2011-12-01)Increasing chronological age is the most significant risk factor for cancer. Recently, we proposed a new paradigm for understanding the role of the aging and the tumor microenvironment in cancer onset. In this model, cancer cells induce oxidative stress in adjacent stromal fibroblasts. This, in turn, causes several changes in the phenotype of the fibroblast including mitochondrial dysfunction, hydrogen peroxide production, and aerobic glycolysis, resulting in high levels of L-lactate production. L-lactate is then transferred from these glycolytic fibroblasts to adjacent epithelial cancer cells and used as "fuel" for oxidative mitochondrial metabolism. Here, we created a new pre-clinical model system to directly test this hypothesis experimentally. To synthetically generate glycolytic fibroblasts, we genetically-induced mitochondrial dysfunction by knocking down TFAM using an sh-RNA approach. TFAM is mitochondrial transcription factor A, which is important in functionally maintaining the mitochondrial respiratory chain. Interestingly, TFAM-deficient fibroblasts showed evidence of mitochondrial dysfunction and oxidative stress, with the loss of certain mitochondrial respiratory chain components, and the over-production of hydrogen peroxide and L-lactate. Thus, TFAM-deficient fibroblasts underwent metabolic reprogramming towards aerobic glycolysis. Most importantly, TFAM-deficient fibroblasts significantly promoted tumor growth, as assayed using a human breast cancer (MDA-MB-231) xenograft model. These increases in glycolytic fibroblast driven tumor growth were independent of tumor angiogenesis. Mechanistically, TFAM-deficient fibroblasts increased the mitochondrial activity of adjacent epithelial cancer cells in a co-culture system, as seen using MitoTracker. Finally, TFAM-deficient fibroblasts also showed a loss of caveolin-1 (Cav-1), a known breast cancer stromal biomarker. Loss of stromal fibroblast Cav-1 is associated with early tumor recurrence, metastasis, and treatment failure, resulting in poor clinical outcome in breast cancer patients. Thus, this new experimental model system, employing glycolytic fibroblasts, may be highly clinically relevant. These studies also have implications for understanding the role of hydrogen peroxide production in oxidative damage and "host cell aging," in providing a permissive metabolic microenvironment for promoting and sustaining tumor growth.
Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: risks of breast/ovarian cancer quoted should reflect the cancer burden in the family.Evans, D Gareth R; Shenton, Andrew; Woodward, Emma; Lalloo, Fiona; Howell, Anthony; Maher, Eamonn R; Academic Unit of Medical Genetics and Regional Genetics Service, St Mary's Hospital Manchester M13 0JH, UK. email@example.com (2008)BACKGROUND: The identification of a BRCA1 or BRCA2 mutation in familial breast cancer kindreds allows genetic testing of at risk relatives. However, considerable controversy exists regarding the cancer risks in women who test positive for the family mutation. METHODS: We reviewed 385 unrelated families (223 with BRCA1 and 162 with BRCA2 mutations) ascertained through two regional cancer genetics services. We estimated the penetrance for both breast and ovarian cancer in female mutation carriers (904 proven mutation carriers - 1442 females in total assumed to carry the mutation) and also assessed the effect on penetrance of mutation position and birth cohort. RESULTS: Breast cancer penetrance to 70 and to 80 years was 68% (95%CI 64.7-71.3%) and 79.5% (95%CI 75.5-83.5%) respectively for BRCA1 and 75% (95%CI 71.7-78.3%) and 88% (95%CI 85.3-91.7%) for BRCA2. Ovarian cancer risk to 70 and to 80 years was 60% (95%CI 65-71%) and 65% (95%CI 75-84%) for BRCA1 and 30% (95%CI 25.5-34.5%) and 37% (95%CI 31.5-42.5%) for BRCA2. These risks were borne out by a prospective study of cancer in the families and genetic testing of unaffected relatives. We also found evidence of a strong cohort effect with women born after 1940 having a cumulative risk of 22% for breast cancer by 40 years of age compared to 8% in women born before 1930 (p = 0.0005). CONCLUSION: In high-risk families, selected in a genetics service setting, women who test positive for the familial BRCA1/BRCA2 mutation are likely to have cumulative breast cancer risks in keeping with the estimates obtained originally from large families. This is particularly true for women born after 1940.