Treatment Of Cervix Cancer Research Articles

SU‐E‐T‐515: Comparison of Two Dose‐Specification Methods for the Treatment of Uterine Cervix Cancer with HDR Brachytherapy Using a Tandem and Ring Applicator

To compare the dose to the high-risk clinical target volume (HRCTV)-D90 and dose-limiting structures with the dose prescription to point A (Manchester system) using conventional methods to image-guided treatment planning with dose optimization and a dose prescription to D90 of the HRCTV. CT-MR-fused image sets for 16 patients (stage IA2-IIIB) with uterine cervix cancer were obtained for each of 5 fractions of HDR brachytherapy using tandem and ring applicators to generate 2 sets of plans. In the first set, the dose was prescribed to point A with a standard dwell weight pattern reflecting the Manchester system loading pattern. In the second set, the dose was prescribed to D90 of the HRCTV with graphical plan optimization. Parameters of clinical significance (HRCTV-D90 and dose received by 1.0, 2.0, and 5.0cc of the bladder, rectum, and sigmoid) were compared, as recommended by GEC-ESTRO. HRCTV-V for 6 patients was =30cc (largest radius, <2.0cm) and >30cc (largest radius, =2cm) for the others. For the first set of plans, when HRCTV-V was <30cc, the ratio of doses HRCTV-D90/dose to point A varied from 1.10 to 1.40. When HRCTV-V was >30cc, it varied from 0.75 to 0.95. In the second set of plans, HRCTV-D90 always received the prescription dose. Doses to 2cc of one or more organs at risk exceeded >10% of the limiting doses for 9 patients in the first set of plans but remained <10% in all patients in the second set of plans. A 10-25% dose reduction to 2cc of the bladder and 15-35% to 2cc of the rectum and sigmoid occurred in the second set of plans. Image-guided brachytherapy with dose optimization yields a prescribed dose to the HRCTV-D90 while maintaining doses to organs at risk close to their limiting value, offering a dosimetric benefit over the traditional method.

SU-E-J-179: Requirements for the Accuracy of Electron Density Data Planning for MRI Based Cervix Cancer Treatment Planning.

A sensitivity analysis of the effect of variations in electron density data (ED) on dose calculation accuracy for MRI based cervical cancer treatment planning. Five cervical cancer patients were analysed in this work. Planning CT scans represented gold standard ED data. Standard four field 3DCRT plans (prescription 45Gy) were designed on these CT scans. The CT data was then manipulated to simulate the following methods of assigning ED to MRI; (1) homogenous bulk density corrections, (2) Bulk density correction to bones, (3) rigid image registration of CT to MR, and (4) regression analysis based pseudo CT. Plans were then generated on the manipulated data sets, and compared to the plans generated on the original. Dose was analysed using Chi analysis and equivalent uniform dose (EUD). Data was analysed to quantify (A) the effect on plan design (called optimisation error), and (B) the effect on dose calculation accuracy (systematic error). Analysis of the averaged patient results showed that for 3DCRT, the use of imperfect electron density data had minimal impact on plan design for all tested data sets. Analysis of systematic error showed minimal errors for cases (1), (2) and (3), where average errors of less than 0.3 Gy in EUD were recorded and Chi analysis showed that over 95% of points within the high dose region (D>36Gy) were within 2% or 2mm of the original dose. For case (4), errors greater than .5 Gy in EUD were recorded; these were not considered acceptable errors. Using imperfect electron density data for 3DCRT treatment planning for cervical cancer patients is feasible for appropriately considered choices of electron density assignment. Further analysis is needed to test this result for IMRT, and is ongoing.

TH-E-BRA-08: MR Guided Radiotherapy for Cervix Cancer Treatment; Retrospective Feasibility Study

Purpose: To evaluate the efficacy of on-line MR guided radiotherapy for cervix cancer patients. MR guidance was simulated in order to optimize the fractional dose to the on-line targets. Methods: 33 cervical cancer patients underwent planning and weekly pelvic MRI scans during radiotherapy. In the previous retrospective adaptive planning study using 3 mm PTV margin, 5 over 33 patient cases were identified and enrolled in this study in which the coverage of GTV/CTVs was not acceptable with single IMRT adaptation with bone matching. MR guidance was simulated in order to maximize online high risk CTV (HRCTV) volume to be within 95% of the prescription dose (95p). Fractional dose after the image guidance was calculated, and was deformed back to the reference (planning) image for dose accumulation. Accumulated dose of the proposed technique was compared with that of current standard image guidance technique, bone matching in terms of the target coverage (cervix, GTV, HRCTV, lower uterus, parametria, and upper vagina) and OAR sparing (bladder, bowl, rectum, and sigmoid). Target coverage was considered acceptable if 95p dose or more was delivered to 98% of the target volume. OAR sparing was evaluated with accumulated V45 and D2cc. Results: On line MR based soft tissue guidance proposed in this study achieved the acceptance of target coverage to 97% from 53% (bone matching). Dose delivery to HRCTV and lower uterus was significantly improved (p<0.001, paired t-test). The mean D2cc and V45 were reduced in bladder, rectum and sigmoid compared to bone matching. Conclusions: The retrospective study revealed that the on-line MR based soft-tissue image guidance is very effective for cervix cancer treatment. The technique significantly and successfully improved target coverage for the most difficult patient group identified from the previous study. Statistically significant improvement in OAR sparing was also noted. Anna Lundin and Henrik Rehbinder are both employees and shareholders of RaySearch Laboratories AB. All other authors have no conflicts to report.

Estimation of Homeostatic Activity of the Human Body and Its Systems in Treatment of Uterine Cervix Cancer

Changes in homeostatic parameters of the human body and its systems caused by chemotherapy and radiation therapy can be assessed by complex monitoring of peripheral blood parameters (AKS-ENOFIT system). Such monitoring shows changes in the dynamic curves of patient body state and their dependence on radiation dose. In contrast to radiation therapy, the zigzag shape of these curves becomes more pronounced at lower radiation doses. This is due to the homeostasis phenomenon and can be regarded as evidence of regulation of homeostasis.

Rebuttal to Drs. Lindegaard and Tanderup

There is no doubt that significant and important advances have been made in the evolution of brachytherapy in cervix cancer treatment in recent years. As Lindegaard and Tanderup describe, development of new applicator systems enabling dose delivery beyond Point A and the collaborative development and adoption of image-guided adaptive brachytherapy techniques by the Groupe Europ een de Curieth erapie (GEC) and the European Society for Therapeutic Radiology and Oncology (ESTRO) has renewed enthusiasm and appreciation of the benefits of brachytherapy. However, since the publication of GEC-ESTRO guidance in 2005 recent patterns of care studies suggest that the resources required to perform this complex process are beyond the reach of most (1e4). Surveys conducted in Canada, Australia, UK, and by theGynecologicCancer InterGroup (GCIG) demonstrate that between only 5% and 20% of centers in these developed countries have access to MRI and while more may be using CT-based planning, a significant proportion remain reliant on two-dimensional imaging. The initial purchase and maintenance of the increasingly technical hardware required for image-guided adaptive brachytherapy (IGABT) is costly and the acquisition of the skills to perform complex insertions is time consuming. When compared, the software required to plan and deliver complex external beam can be used throughout the radiotherapy department across tumor sites. A range of dose fractionation schedules are described for IGABT with no clear consensus on how to combine this with the external beam component of treatment. These schedules seem to offer equivalent total doses but rely on an assumption that the isoeffective dose calculation holds true irrespective of overall time. Similarly, as Lindegaard and Tanderup point out, how to combine doseevolume histogram parameters from external beam schedules with those suggested for brachytherapy remains unclear.

Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy for the definitive treatment of cervix cancer

Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy for the definitive treatment of cervix cancer

Treatment of stage IB1 cervix cancer: Comparison of radical hysterectomy and radiation

Objective: Radical hysterectomy and radiotherapy have long been mainstays of treatment for early stage cervix cancer and their equivalency established over decades of research. Two recently published studies using SEER data concluded that surgical management is superior to radiotherapy. We sought to review similar data in a retrospective, single-institution format. Our aim was to compare the recurrence rates, complications, and survival of women with stage IB1 cervical cancer treated by primary radical hysterectomy versus radiation.

An integrated approach to segmentation and nonrigid registration for application in image-guided pelvic radiotherapy

External beam radiotherapy (EBRT) has become the preferred options for nonsurgical treatment of prostate cancer and cervix cancer. In order to deliver higher doses to cancerous regions within these pelvic structures (i.e. prostate or cervix) while maintaining or lowering the doses to surrounding non-cancerous regions, it is critical to account for setup variation, organ motion, anatomical changes due to treatment and intra-fraction motion. In previous work, manual segmentation of the soft tissues is performed and then images are registered based on the manual segmentation. In this paper, we present an integrated automatic approach to multiple organ segmentation and nonrigid constrained registration, which can achieve these two aims simultaneously. The segmentation and registration steps are both formulated using a Bayesian framework, and they constrain each other using an iterative conditional model strategy. We also propose a new strategy to assess cumulative actual dose for this novel integrated algorithm, in order to both determine whether the intended treatment is being delivered and, potentially, whether or not a plan should be adjusted for future treatment fractions. Quantitative results show that the automatic segmentation produced results that have an accuracy comparable to manual segmentation, while the registration part significantly outperforms both rigid and nonrigid registration. Clinical application and evaluation of dose delivery show the superiority of proposed method to the procedure currently used in clinical practice, i.e. manual segmentation followed by rigid registration.

The value of colposcopy, high risk HPV-DNA and histopathologic examination in the management of abnormal Pap smear results

SUMMARY Objective: Pap smear test is a major screening test for early diagnosis and treatment of cervix cancer. The aim of our study was to assess the value of HPV-DNA, colposcopy and histopathologic examination in the management of patients with abnormal cervical cytology. Materials and methods: This prospective cohort study was conducted in Ankara University Cebeci Hospital gynecology outpatient clinic. The study compromised 86 patients with smear results of ASCUS, AGC, L-SIL and H-SIL. Age, gravity, parity, age at first coitus, smoking status, number of partners, high risk HPV-DNA status and pathologic colposcopy findings were investigated. Results: Mean age of the patients was 35 years and the most common abnormal smear result was ASCUS, with 55 patients (63%). There was no significant difference between the groups regarding demographic characteristics except age at first coitus and pathologic colposcopy findings. Among patients diagnosed as ASCUS 34.5% had been upgraded with histopathologic examination. Among patients diagnosed as L-SIL 73.6% had been down-graded with histopathologic examination. However, after the histopathologic exam of 9 H-SIL patients two (22.2%) were diagnosed as CIN II, two (22.2%) were diagnosed as CIN III and one (11.1%) was diagnosed as cervical cancer. In the groups of ASCUS, L-SIL and H-SIL the presence of high risk HPV-DNA were 11%, 5% and 33%, respectively. Conclusion: If we are sure that the patient will attend the follow-up visits, then for the ones with ASCUS and L-SIL a repeat smear test would be the appropriate. However, in the management of patients with H-SIL colposcopic biopsy would be the best approach.

Rhein Lysinate Induced S-Phase Arrest and Increased the Anti-Tumor Activity of 5-FU in HeLa Cells

Rhein lysinate (RHL), easily dissolved in water, is one of the anthraquinones, and has been shown to have anti-tumor activity in different human cancer cell lines. In the present study, we observed that RHL could cause vacuolar degeneration in HeLa cells, which was not observed in human umbilical vein endothelial cells (HUVECs) and other cell lines (SKOV-3 and SK-BR-3). Therefore, the purpose of this study was to investigate the anti-tumor effect of rhein lysinate on human cervix cancer HeLa cells. The results indicated that RHL could induce HeLa cell S-phase arrest and RHL (higher than 80 μM) also induced HeLa cell G2/M-phase arrest in a dose-dependent manner. Compared to the HeLa cells, RHL induced HUVECs G1-phase arrest at all dose levels tested in a dose-dependent manner. Treatment with RHL led to a significant S or G2/M-phase arrest through promoting the expression of p53 and p21 and the phosphorylation of p53. Moreover, 80 μM RHL could increase 5-FU anti-tumor activity. In conclusion, RHL could be a novel chemotherapeutic drug candidate for the treatment of human cervix cancer in the future.

Interactive multiobjective optimization for anatomy-based three-dimensional HDR brachytherapy

In this paper, we present an anatomy-based three-dimensional dose optimization approach for HDR brachytherapy using interactive multiobjective optimization (IMOO). In brachytherapy, the goals are to irradiate a tumor without causing damage to healthy tissue. These goals are often conflicting, i.e. when one target is optimized the other will suffer, and the solution is a compromise between them. IMOO is capable of handling multiple and strongly conflicting objectives in a convenient way. With the IMOO approach, a treatment planner's knowledge is used to direct the optimization process. Thus, the weaknesses of widely used optimization techniques (e.g. defining weights, computational burden and trial-and-error planning) can be avoided, planning times can be shortened and the number of solutions to be calculated is small. Further, plan quality can be improved by finding advantageous trade-offs between the solutions. In addition, our approach offers an easy way to navigate among the obtained Pareto optimal solutions (i.e. different treatment plans). When considering a simulation model of clinical 3D HDR brachytherapy, the number of variables is significantly smaller compared to IMRT, for example. Thus, when solving the model, the CPU time is relatively short. This makes it possible to exploit IMOO to solve a 3D HDR brachytherapy optimization problem. To demonstrate the advantages of IMOO, two clinical examples of optimizing a gynecologic cervix cancer treatment plan are presented.

Radiochemotherapy versus chemotherapy in locally advanced cervix cancer: A pilot study.

e15561 Background: Many reports have correlated 1) hypoxia with attenuated responses to radiotherapy and 2) a good oxygenation as function of high HGB level in the peripheral blood. There is agreement to increase to the response to the radiotherapy of head and neck with the use of erythropoietin to increase the hemoglobin level. Methods: From January 2002 until January 2009 we treated 88 patients with cervix locally advanced, 26 patients in stage IIB, 28 in stage IIIA 20 in stage III B and 14 patients in IV stage. 44 patients previously treated with chemotherapy (cisplatin, ifosfamide, paclitaxel), the response of chemotherapy was 12 PR,7NC,3 PD. All patients had an HGB between 9 and 12 gr/dL and from 2 weeks before radiotherapy we daily treated with erythropoietin 10,000 UI to increase HGB between 13 and 14 gr/dL, then we gave erythropoietin every day with radiotherapy. In the second group 44 patients were treated with radiotherapy plus 5FU 1g/sm/day, days 1-5, continuous iv infusion + carboplatino 80 mg and erythropoietin. Results: We have analyzed the patients one month after radiotherapy we valued the result of the treatment. Only in 28 /44 patients we used to increase the HGB to 13-14 gr, in the other 8 patients (37% ) the value of HGB was between 9-11 gr. The response to radiotherapy was 26 PR, 16 NC and 2 PD. The response of the second treatment was 15 CR,7 PR. In 8/44 we used to interrupt treatment for III grade of leuko-thrombocytopenia. Conclusions: In patients, previously treated with chemotherapy, the residual disease is probably hypoxic and therefore is radio-resistant for this reason does not increase the efficacy of radiotherapy nonstante the value of HGB between 13-14 gr, after chemotherapy we had a compromised bone marrow hence we coclude that it is difficult to increase the value of hgb after chemotherapy for bone marrow failure. We are continuing the radiotherapy in concomitant with 5FU plus carboplatin and erytropoeitin in the first choice of treatment of cervix cancer locally advanced seeing the good response 30/44 patients with complete response and 14 /44 partial response No significant financial relationships to disclose.

Consensus Guidelines for Delineation of Clinical Target Volume for Intensity-Modulated Pelvic Radiotherapy for the Definitive Treatment of Cervix Cancer

Accurate target definition is vitally important for definitive treatment of cervix cancer with intensity-modulated radiotherapy (IMRT), yet a definition of clinical target volume (CTV) remains variable within the literature. The aim of this study was to develop a consensus CTV definition in preparation for a Phase 2 clinical trial being planned by the Radiation Therapy Oncology Group. A guidelines consensus working group meeting was convened in June 2008 for the purposes of developing target definition guidelines for IMRT for the intact cervix. A draft document of recommendations for CTV definition was created and used to aid in contouring a clinical case. The clinical case was then analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with kappa statistics as a measure of agreement between participants. Nineteen experts in gynecological radiation oncology generated contours on axial magnetic resonance images of the pelvis. Substantial STAPLE agreement sensitivity and specificity values were seen for gross tumor volume (GTV) delineation (0.84 and 0.96, respectively) with a kappa statistic of 0.68 (p < 0.0001). Agreement for delineation of cervix, uterus, vagina, and parametria was moderate. This report provides guidelines for CTV definition in the definitive cervix cancer setting for the purposes of IMRT, building on previously published guidelines for IMRT in the postoperative setting.

Hospital Morbidity through Cervical Cancer - Romania, 2009

Cancer is responsible for a large share of deaths, worldwide as well as in Romanaia, and induces high costs (for individuals, health system and society), proved to be one of the most burdensome diseases. Lately, problems induced by cancer in women are increasing, due to the raise in incidence, but mainly to the high mortality rate of cervix cancer. Hospitals having obstetrics-gynecology departments are the main medical units who provide specialized services for diagnosis, staging and treatment of cervix cancer; the most of cervix cancers cases are recorded in hospital care sector, and the analysis of hospital morbidity may offer a pretty fair picture of the phenomenon. The present paper presents some results of the analysis of the hospital morbidity trough cervix cancer, in hospitals who reported clinical data at patient level, during the first eight months of the year 2009. Key words: geographic distribution of hospitalizations, the profile of hospitalization, surgical procedures for cervix cancer in hospital

Variability in Delineation of Clinical Target Volumes for Cervix Cancer Intensity-modulated Pelvic Radiotherapy

Accurate target definition is vitally important for definitive treatment of cervix cancer with intensity-modulated radiotherapy (IMRT), yet clinical target volumes (CTV) definitions remain variable within the literature. In a survey of patterns of practice among members of the RTOG, GOG, NCIC, and JGOG, variation was seen in the definition of specific CTV components and the planning margins used. Therefore, the aim of this study was to evaluate the variability in CTV definition in preparation for a planned RTOG Phase II clinical trial.

Presentation of Chemotherapy Options for Cervix Cancer on Cancer-Related Internet Sites

There are limited data available in the medical literature concerning the issue of the depth of information presented on cancer-related Internet-based dealing with disease management. To explore this question, websites identified on a popular search engine (Google) employing the search strategy, "treatment of cervix cancer," were evaluated for their presentation of chemotherapy-related topics, including possible strategies supported by solid evidence-based data (e.g., concurrent chemotherapy plus radiation) and programs likely to have limited impact on the course of the illness (e.g., progression following a cisplatin-based chemoradiation regimen). Of 66 websites identified, 92% mentioned chemotherapy as a possible treatment for cervix cancer. However, although 51% noted the option of chemoradiation, only 18% stated this approach had been shown to improve survival. Further, discussions of the specific toxicity of chemotherapy for cervix cancer were uncommon (12%), and mention of a management strategy that focuses exclusively on supportive and comfort care measures in the setting of progressive and platinum-resistant disease was rare (3%). Although generally technically accurate, the content of the information describing the role of chemotherapy within Internet sites dealing with cervix cancer is superficial and likely of limited educational value.

SU‐FF‐T‐35: A Monte Carlo Study for Evaluation of Tissue Heterogeneity Effect of Inversely Optimized Intracavitary High Dose Rate Brachytherapy Plan

Purpose: To investigate tissue heterogeneity effect of an intracavitary high dose rate brachytherapy plan which is optimized by the inverse planning option. Method and Materials: A CT and VOI based brachytherapy plan for an intra‐uterine and cervix cancer treatment was made using inverse planning simulated‐annealing (IPSA) module provided by Plato TPS. The microSelectron‐HDR Ir‐192 afterloader and 3 catheters (2 ovoids and 1 tandem) were used for the treatment. For a verification of the plan result, EGSnrc based dosxyznrc Monte Carlo code was employed. Patient CT data was converted to egsphant data by the ctcreate code and each source position and weight from the plan data was used for a Monte Carlo simulation as well. Ir‐192 source was approximately modeled by 3.6 mm length and 0.6 mm diameter and it was assumed to be located at the center of the catheters, while parallel to the z‐axis at each position because of restricted freedom of source modeling. The microSelectron‐HDR Ir‐192 spectrum data could be obtained from the EGSnrc code, however, number of history was determined empirically based on known air‐kerma and dose rate value. Conventional point A and B doses and DVHs of PTV, bladder and rectum were evaluated for a quantitative comparison. Results: Significant decrease of dose at point A and B more than 10% was observed in the Monte Carlo simulation. PTV coverage by 100% isodose surface was degraded while rectum and bladder mean dose was reduced up to 15%. Resultant dose rate decrease was also observed. Conclusion: Conventional brachytherapy dose calculation method could not appropriately consider tissue heterogeneity effect and inverse planning optimization could invoke serious erroneous result. Therefore inverse planning optimization should be carefully implemented for a HDR brachytherapy planning.

Evaluation of toxicity of surgery and/or chemoirradiation treatment of uterine cervix cancer

To evaluate acute and chronic toxicity of chemoirradiation treatment (neoadjuvant, adjuvant and radical treatment) in patients diagnosed with cervix cancer. From December 1999 to August 2007, 53 patients diagnosed with adenocarcinoma or squamous cell carcinoma of the uterine cervix received neoadjuvant, adjuvant or radical chemoirradiation. Acute gastrointestinal toxicity of grade 3 or more in 9 patients (17%) and haematological toxicity of grade 3 or more in 9 patients (17%). Chronic toxicity of grade 3 or more was shown in only 2 patients (4%). The most frequent toxicities were gastrointestinal toxicity and haematological toxicity. The most frequent chronic toxicities were gastrointestinal toxicity and vaginal toxicity. We report that the combined neoadjuvant, adjuvant or radical chemoirradiation treatment with weekly cisplatin chemotherapy (40 mg/m(2)/week) in patients diagnosed with cervix cancer is a well tolerated treatment and chronic and acute toxicity is low-grade. This treatment scheme has easy compliance.

Toxicity after Cervical Cancer Treatment using Radiotherapy and Chemotherapy

The increasing concern at toxicity rates after radiotherapy and concomitant cytotoxic chemotherapy has prompted this viewpoint of basic scientific mechanisms. Toxicity is a function of many controllable treatment-related variables: external beam technique; dose and fractionation; brachytherapy volume, dose and dose rate; and chemotherapy sensitisation of normal tissues. To obtain optimal results, detailed attention must be given to all these factors. For chemotherapy-related toxicity, a hypothesis is suggested for testing in clinical trials: the use of chemotherapy immediately before radiotherapy may sensitise normal tissues to a much greater extent than if given a few hours later, when platinum will no longer be in an ionised state, but will be protein bound. It may also be preferable to use the platinum after all radiotherapy exposures each week, in order to prevent compounding of incomplete repair of sublethal DNA damage and reduce its conversion into lethal damage. Because the dose intensity of the platinum schedules is as high as in ovarian cancer, it is assumed that the action on tumour cells is independent cell kill, so that the temporal pattern of administration will not be as important. Further analysis of patients treated at the Clatterbridge and Hammersmith hospitals is suggested, because of the low level of serious morbidity found there using different approaches, including the above chemotherapy scheduling. A better national approach to the treatment and study of cervix cancer is indicated, with quality of life as an important outcome measure, as well as survival.

The Gynecologic Oncology Group's role in the treatment of recurrent cervix cancer: Current clinical trials

The Gynecologic Oncology Group's role in developing and evaluating vital research hypotheses for women with cancer of the uterine cervix cannot be understated, as methodical and interpretable conclusions from its many clinical studies have defined, supported and driven the standard of care in several avenues of clinical care. The focus of this presentation was to review for an international audience the principle structure, underlying hypotheses and historical progress in the investigation of chemotherapy options for women identified with recurrent cervix cancer. While the impact of phase II research queues were presented, the primary focus was to review the pivotal randomized trial which now define practice standards for these women.