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      Radiation Therapy with Concurrent Chemotherapy for Locally Advanced Cervical Carcinoma: Outcome Analysis with Emphasis on the Impact of Treatment Duration on Outcome

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          Abstract

          Objective. To assess the effectiveness and toxicity of carboplatin concurrent with pelvic external beam radiation and low-dose rate brachytherapy and to assess the impact that adherence to the treatment plan has on outcomes. Methods. Retrospective chart review of 56 patients treated from January 2001 to December 2010. Results. Median follow-up was 68 months. Optimal dose of radiation (ORT) was defined as a minimal cervical dose exceeding 70 Gy, point A dose of 80–90 Gy, and duration not exceeding 56 days. Only 50% received ORT. In multivariable analyses we only found ORT to be statistically significant predictor for progression-free survival (PFS) and overall survival (OS) (HR [95% CI] for non-ORT vs. ORT: 2.4 [1.2, 5.1], P = 0.014 for PFS and 2.2 [1.1, 4.6], P = 0.035 for OS). The 5-year PFS in patients who received ORT was better than that in patients who received non-ORT, 56% vs. 22% (95% CI: [36%, 72%] vs. [9%, 39%]). Patients who received ORT had a better 5-year OS as well (59% vs. 33%; 95% CI: [38%, 75%] vs. [16%, 51%]). Conclusion. Patients with locally advanced cervical cancer treated with weakly carboplatin or cisplatin, teletherapy, and low dose-dose rate brachytherapy have poorer outcomes when treatment duration is prolonged.

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          Carboplatin dosage: prospective evaluation of a simple formula based on renal function.

          A H Calvert, D Newell, L. Gumbrell … (1989)
          A dosage formula has been derived from a retrospective analysis of carboplatin pharmacokinetics in 18 patients with pretreatment glomerular filtration rates (GFR) in the range of 33 to 136 mL/min. Carboplatin plasma clearance was linearly related to GFR (r = 0.85, P less than .00001) and rearrangements of the equation describing the correlation gave the dosage formula dose (mg) = target area under the free carboplatin plasma concentration versus time curve (AUC) x (1.2 x GFR + 20). In a prospective clinical and pharmacokinetic study the formula was used to determine the dose required to treat 31 patients (GFR range, 33 to 135 mL/min) with 40 courses of carboplatin. The target AUC was escalated from 3 to 8 mg carboplatin/mL/min. Over this AUC range the formula accurately predicted the observed AUC (observed/predicted ratio 1.24 +/- 0.11, r = 0.886) and using these additional data, the formula was refined. Dose (mg) = target AUC x (GFR + 25) is now the recommended formula. AUC values of 4 to 6 and 6 to 8 mg/mL. min gave rise to manageable hematological toxicity in previously treated and untreated patients, respectively, and hence target AUC values of 5 and 7 mg/mL min are recommended for single-agent carboplatin in these patient groups. Pharmacokinetic modeling demonstrated that the formula was reasonably accurate regardless of whether a one- or two-compartment model most accurately described carboplatin pharmacokinetics, assuming that body size did not influence nonrenal clearance. The validity of this assumption was demonstrated in 13 patients where no correlation between surface area and nonrenal clearance was found (r = .31, P = .30). Therefore, the formula provides a simple and consistent method of determining carboplatin dose in adults. Since the measure of carboplatin exposure in the formula is AUC, and not toxicity, it will not be influenced by previous or concurrent myelosuppressive therapy or supportive measures. The formula is therefore applicable to combination and high-dose studies as well as conventional single-agent therapy, although the target AUC for carboplatin will need to be redefined for combination chemotherapy.
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            Persistent area socioeconomic disparities in U.S. incidence of cervical cancer, mortality, stage, and survival, 1975-2000.

            L. Miller, Molly Edwards, G. Singh … (2004)
            Temporal cervical cancer incidence and mortality patterns and ethnic disparities in patient survival and stage at diagnosis in relation to socioeconomic deprivation measures have not been well studied in the United States. The current article analyzed temporal area socioeconomic inequalities in U.S. cervical cancer incidence, mortality, stage, and survival. County and census tract poverty and education variables from the 1990 census were linked to U.S. mortality and Surveillance, Epidemiology, and End Results cancer incidence data from 1975 to 2000. Age-adjusted incidence and mortality rates and 5-year cause-specific survival rates were calculated for each socioeconomic group and differences in rates were tested for statistical significance at the 0.05 level. Substantial area socioeconomic gradients in both incidence and mortality were observed, with inequalities in cervical cancer persisting against a backdrop of declining rates. Cervical cancer incidence and mortality rates increased with increasing poverty and decreasing education levels for the total population as well as for non-Hispanic white, black, American Indian, Asian/Pacific Islander, and Hispanic women. Patients in lower socioeconomic census tracts had significantly higher rates of late-stage cancer diagnosis and lower rates of cancer survival. Even after controlling for stage, significant differences in survival remained. The 5-year survival rate among women diagnosed with distant-stage cervical cancer was approximately 30% lower in low than in high socioeconomic census tracts. Census-based socioeconomic measures such as area poverty and education levels could serve as important surveillance tools for monitoring temporal trends in cancer-related health inequalities and targeting interventions. Copyright 2004 American Cancer Society.
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              The effect of treatment time in locally advanced cervical cancer in the era of concurrent chemoradiotherapy.

              Suisui Song, Sonali Rudra, Michael Hasselle … (2013)
              This study sought to determine if treatment time impacts pelvic failure (PF), distant failure (DF), or disease-specific mortality (DSM) in patients undergoing concurrent chemoradiotherapy (CCRT).
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                Author and article information

                Journal
                Journal ID (nlm-ta): Obstet Gynecol Int
                Journal ID (iso-abbrev): Obstet Gynecol Int
                Journal ID (publisher-id): OGI
                Title: Obstetrics and Gynecology International
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 1687-9589
                ISSN (Electronic): 1687-9597
                Publication date (Print): 2014
                Publication date (Electronic): 5 November 2014
                Volume: 2014
                Electronic Location Identifier: 214351
                Affiliations
                1Department of Obstetrics, Gynecology and Reproductive Sciences, Temple University Hospital, Temple University School of Medicine, 3401 N. Broad Street, Philadelphia, PA 19140, USA
                2Department of Clinical Sciences, Temple Clinical Research Center, Temple University Hospital, Temple University School of Medicine, Philadelphia, PA 19140, USA
                3Department of Radiation Oncology, Temple University Hospital, Temple University School of Medicine, Philadelphia, PA 19140, USA
                Author notes
                *Enrique Hernandez: ehernand@ 123456temple.edu

                Academic Editor: Thomas Herzog

                Author information
                http://orcid.org/0000-0003-1034-3130
                http://orcid.org/0000-0003-3264-994X
                Article
                DOI: 10.1155/2014/214351
                PMC ID: 4238273
                SO-VID: 72df04c4-69de-4eff-972e-ae09dc15a336
                Copyright © Copyright © 2014 Juan Diaz et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 7 July 2014
                Date revision received : 29 September 2014
                Date accepted : 13 October 2014
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Obstetrics & Gynecology
                Data availability:
                ScienceOpen disciplines: Obstetrics & Gynecology

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