Cervix Cancer Patients Research Articles

Patterns of care study of brachytherapy in New South Wales: cervical cancer treatment quality depends on caseload.

PurposeWe previously conducted modelling and a patterns of care study (POCS) that showed gynaecological brachytherapy (BT) was underutilized in New South Wales (NSW), the USA and Western Europe. The aim of the current study was to assess the quality of cervical BT in NSW, and to determine if caseload affects quality of treatment delivery.Material and methodsAll nine NSW radiation oncology departments that treated patients with cervical BT in 2003 were visited. Patient, tumour and treatment related data were collected. Quality of BT was assessed using published quality benchmarks. Higher and lower caseload departments were compared.ResultsThe four higher cervical BT caseload departments treated 11-15 NSW residents in 2003, compared to 1-8 patients for the lower caseload departments. Cervix cancer patients treated at the higher caseload departments were more likely to be treated to a point A dose ≥ 80 Gy (58% vs. 14%, p = 0.001), and to have treatment completed within 8 weeks (66% vs. 35%, p = 0.02). Despite higher point A doses, there was no significant difference in proportions achieving lower than recommended rectal or bladder doses, implying better BT insertions in higher caseload departments.ConclusionsCervical BT in NSW was dispersed amongst a large number of departments and was frequently of sub-optimal quality. Higher quality BT was achieved in departments treating at least 10 patients per year. It is likely that improved outcomes will be achievable if at least 10 patients are treated per department per year.

High-risk clinical target volume delineation in CT-guided cervical cancer brachytherapy: Impact of information from FIGO stage with or without systematic inclusion of 3D documentation of clinical gynecological examination

Purpose. The aim of the study was to improve computed tomography (CT)-based high-risk clinical target volume (HR CTV) delineation protocols for cervix cancer patients, in settings without any access to magnetic resonance imaging (MRI) at the time of brachytherapy. Therefore the value of a systematic integration of comprehensive three-dimensional (3D) documentation of repetitive gynecological examination for CT-based HR CTV delineation protocols, in addition to information from FIGO staging, was investigated. In addition to a comparison between reference MRI contours and two different CT-based contouring methods (using complementary information from FIGO staging with or without additional 3D clinical drawings), the use of standardized uterine heights was also investigated. Material and methods. Thirty-five cervix cancer patients with CT- and MR-images and 3D clinical drawings at time of diagnosis and brachytherapy were included. HR CTVstage was based on CT information and FIGO stage. HR CTVstage + 3Dclin was contoured on CT using FIGO stage and 3D clinical drawing. Standardized HR CTV heights were: 1/1, 2/3 and 1/2 of uterine height. MRI-based HR CTV was delineated independently. Resulting widths, thicknesses, heights, and volumes of HR CTVstage, HR CTVstage + 3Dclin and MRI-based HR CTV contours were compared. Results. The overall normalized volume ratios (mean± SD of CT/MRIref volume) of HR CTVstage and HR stage + 3Dclin were 2.6 (± 0.6) and 2.1 (± 0.4) for 1/1 and 2.3 (± 0.5) and 1.8 (± 0.4), for 2/3, and 1.9 (± 0.5) and 1.5 (± 0.3), for 1/2 of uterine height. The mean normalized widths were 1.5 ± 0.2 and 1.2 ± 0.2 for HR CTVstage and HR CTVstage + 3Dclin, respectively (p < 0.05). The mean normalized heights for HR CTVstage and HR CTVstage + 3Dclin were both 1.7 ± 0.4 for 1/1 (p < 0.05.), 1.3 ± 0.3 for 2/3 (p < 0.05) and 1.1 ± 0.3 for 1/2 of uterine height. Conclusion. CT-based HR CTV contouring based on FIGO stage alone leads to large overestimation of width and volume. Target delineation accuracy can systematically improve through incorporation of additional information from comprehensive 3D documentation of repetitive gynecological examination in the contouring protocol, and thus help to improve the accuracy of dose optimization in settings with limited access to imaging facilities at the time of brachytherapy. If CT information is only available, minimum 2/3 of uterine height may be a good surrogate for the height of HR CTV.

Pelvic MRI to follow-up cervix cancer patients, preliminary results

Pelvic MRI to follow-up cervix cancer patients, preliminary results

SU-E-T-718: Automatic IMRT Plan Quality Control for GYN Cancer Clinical Trials

Purpose: To perform efficient quality control (QC) of intensity‐modulated radiotherapy (IMRT) plans of gynecological (GYN) cancer in clinical trials. Methods: Plan QC is a necessary component in clinical trials that requires much time and effort. IMRT plans from the INTERTECC clinical trial for the treatment of intact cervix cancer patients have been used to evaluate a plan QC tool. The CT image, organ and target contours, and the clinical IMRT plan were imported into a GPU‐based treatment re‐planning system that was originally designed to perform online adaptive radiotherapy. The clinical plan was considered as the reference plan and the re‐planning system automatically created a new plan. The objective for re‐planning was to reduce dose of organs‐at‐risk (OARs) and to get a more uniform dose in the PTV with respect to the reference plan. After performing automatic re‐planning on each plan, we compared the new and the reference DVH curves in terms of the treatment planning goals specified in the clinical trial protocol. Results: Data from 12 patients was retrospectively analyzed. Results showed that DVH curves of the automatic plan satisfy the specified clinical constraints more frequently than the actual clinical plans. DVH for the PTV of the new plan was in most cases similar to the clinical plans, indicating good quality PTV coverage. In 2 out of the 12 cases the QC tool could achieve a PTV hotspots reduction of 11% and 10% respectively. For most patients, lower doses in OARs were achieved after re‐planning, except in those plans where there was overlap between OARs and PTV. Re‐planning takes less than 1 min for each case. Conclusion: We have proved the feasibility of efficient IMRT plan QC in clinical trials for patients with GYN cancer. Varian Medical Systems through a Master Research Agreement

TH‐C‐137‐05: A MOrphing Technique That Projects 3D Surface Objects to a STandard Metric (MOST); Geometric Modeling of Cervix Cancer Patients for Adaptive Radiation Treatment

Purpose: Adaptive radiation therapy (ART) had been proposed based in order to correct the dosimetric discount due to geometric variations by means of feedback control. Numerical modeling of inter‐and intra‐patients' geometric variations is one of the important parts in ART. To this end, a MOrphing technique that projects 3D surface objects to a STandard metric (MOST) was developed. Methods: A total of 174 clinical target volumes (CTVs) were obtained from 32 patients and used to evaluate the MOST. The MOST consists of three main steps; 1) deforming 3D mesh of CTVs to a sphere by parametric active contour (PAC) model, 2) sampling the deformed mesh at evenly distributed girds to be the standard metric, and 3) projecting the 3D data into 2D plane for further analysis. The performance of the MOST was evaluated with respects to 1) iteration number, 2) computation time, and 3) residual deformation, the residual distance between a sphere surface and the deformed node. Result: MOST successfully transformed complex 152 meshes from 28 patients to the standard metric. Convergence was achieved with average iteration of 65 and one standard deviation (STD) of 74 for 137 cases. The computation time was 17.8 hours and this corresponds to 51.3% of the time for all 152 cases. The average±STD of residual deformation was 0.9±0.7‐mm and more than 98% nodes had less than 3‐mm residual deformation. Conclusions: MOST demonstrated its ability to transform complex 3D meshes of cervix cancer into a simple standard metric. Inter‐and intra‐patients' geometric variation could be directly compared and analyzed using the transformed results by virtue of the regularity of standard metric. Numerical modeling of tumor dynamics, implemented using this technique, may provide a systematic way for the estimation of tumor evolution and optimal correctional action for ART. This study is supported by funding from Ray Search Laboratories and Ontario Consortium for Adaptive Interventions Radiation Oncology (OCAIRO).

Abstract 1594: Sustained release of drug eluting nanoparticles from implantable devices for loco-regional chemoradiation therapy.

Abstract Systemic chemotherapy is often used with radiation therapy in the management of prostate, cervix and lung cancer patients, but leads to severe systemic toxicities. We have introduced a new modality of loco-regional chemoradiation therapy termed in-situ image guided radiation therapy (BIS-IGRT) that offers the potential to deliver planned, localized and sustained delivery of chemotherapy agent, without systemic toxicities, as part of routine minimally invasive image guided radiation therapy procedures. Such image guided chemoradiation therapy requires characterization of the drug distribution produced by implantable drug eluters. This work presents imaging based means to measure temporal and spatial properties of diffusion distributions around spacers coated with dye-loaded nanoparticles. The distribution of 250nm silica nanoparticles (NP) conjugated to Cyanine 7.5 dye was evaluated with a custom built high-speed near-infrared small animal imaging platform providing 0.1 millimeter spatial resolution with &amp;gt;1Hz image acquisition rate. A brachytherapy spacer loaded with the Cy7.5/silica NP was injected subcutaneously on the left hind flank of a mouse and one was inserted into a xenograft tumor on the opposite flank as part of an approved animal research protocol. The mouse was imaged more than 36 days. The in vivo imaging experiments show that the area of high signal increases with time suggesting that NP accumulate in the vicinity of a spacer without diffusing to the rest of the body. The spatial and temporal characteristics of NP accumulation indicate that a BIS-IGRT approach may provide an effective means to improve the therapeutic ratio of brachytherapy. Conclusion: In-vivo measurements demonstrate that NP remain resident in the vicinity of the implanted eluting spacers with accumulation over times appropriate to improve brachytherapy's therapeutic ratio. Future work will optimize the NP and substrate properties of an implantable spacer to attain the optimal chemotherapy distributions for simultaneous placement during image guided brachytherapy implants. We acknowledge partial support from NSF DGE 0965843 and HHS/5U54CA151881-02. Citation Format: Rajiv Kumar, Jodi Belz, Stacey Markovic, Tej Jadhav, Paul Nguyen, Mark Niedre, Anthony DAmico, Mike Makrigiorgos, Robert Cormack, Srinivas Sridhar. Sustained release of drug eluting nanoparticles from implantable devices for loco-regional chemoradiation therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1594. doi:10.1158/1538-7445.AM2013-1594

PO-0962: Correlation between DVHs and in-vivo dosimetry measurements in OARs for brachytherapy cervix cancer patients

PO-0962: Correlation between DVHs and in-vivo dosimetry measurements in OARs for brachytherapy cervix cancer patients

A Comparative Study of Result of Treatment of Cancer Cervix Patients Treated by Two Separate Schedules of Radiotherapy

Background: Cervical cancer is the most common cancer of Bangladeshi women diagnosed mostly (&gt;80%) at stage II and stage III. Rdaiotherapy (both teletherapy and brachytherapy) is the most important modality of treatment at these stages.Objective: To compare the local control, diseases free survival and overall survival between the (cancer cervix) patients treated randomly by two schedules of radiotherapy. Method: From June 1996 to June 2005, patients with histologically confirmed carcinoma cervix (Ca.cervix) were treated by external beam therapy (EBRT) as well as intra cavitery brachytherapy (ICRT) along with concurrent/sequential chemotherapy with cisplatin and 5- Fluorouracil. EBRT was given by cobalt60 teletherapy machine and ICRT by caesium137 low dose rate machine. The patients were divided into two groups according to treatment schedules. Group I: the patients in this group received EBRT in whole pelvis in two steps, first with open field upto 10-20 Gy then by applying midline shield with lead block 30-40Gy in 25-28 total fractions, five days a week; they also received 50-70 Gy to point A by ICRT in 2-4 weekly fractions. Group II: patients in this group received with open field a dose of 45-50Gy in 25-28 fractions, 5 days a week by EBRT and 25-30 Gy at point A by ICRT in 1-2 weekly fractions.Result: In Group I, 96 out of 101 and in Group II, 104 out of 118 patients were eligible for evaluation. In both groups patients were distributed according to stages and age more or less equally; their age range were 30-70 years and mean age was 47.2 years in Group I and age range were 25-80 years and mean age was 46 years in Group II. Squamous cell carcinoma were found (90%) and performance status was WHO grade 0-1 (&gt;75%) in both groups. Local control of disease at 5 years was 65% in group I and 51% in group II. Overall survival at 2 years, 5 years, 7 years and 9 years in group I, was 71%, 64%, 55%, 46% and in group II, 54%,50%, 43%,32% respectively. Distant metastasis occurred in 22% in-group I and 28% in-group II. Lymph node, lung, liver, peritoneum were common site of metastasis. Proctitis, cystitis, vaginal stenosis in group I was 80%, 33% 16% and in Group II 29%, 13% and 5% respectively. Conclusion: External beam therapy and brachytherapy was effective treatment in carcinoma. Cervix in both operable and inoperable stages. In small volume of tumor, both schedules of radiotherapy were more or less equivalent but in bulky diseases Group I schedule that was higher dose by brachytherapy at point A showed better result; though the complication was more DOI: http://dx.doi.org/10.3329/bjog.v25i2.13739 Bangladesh J Obstet Gynaecol, 2010; Vol. 25(2) : 50-58

Can Social Support and Control Agency Change Illness Consequences? Evidence from Cervix Cancer Patients

Research has demonstrated facilitative effects of social support on psychological and physical well-being of individuals suffering from chronic health problems. Social support can change not only patients’ perception of their health problems, but also the consequences of their illness. In the present study with cervix cancer patients, the relationship of social support and illness control agency with illness consequences and health outcome beliefs was examined. Emotional, informational, social companionship and practical supports were found to be negatively correlated with the severity of interpersonal, physiological and psychological consequences of illness. Patients’ belief in self-control and doctor-control was related to less severity and less pain of illness, and strong hope for better health outcomes.

Treatment and outcome in cancer cervix patients treated between 1979 and 1994: A single institutional experience

A retrospective review in patients with carcinoma cervix to evaluate the changes and trends in demographics, evolution of protocols, and outcome analysis over 16 years. This is a retrospective study of 6234 patients with carcinoma of the cervix treated with radical intent between 1979 and 1994. All the work-up, staging investigations, treatment details, radiation protocols, outcomes, and toxicities were noted, compiled, and analyzed. With a mean age of 46 years (range: 18-90 years; median: 45 years), 669 (11%) patients were in stage Ib, 284 (5%) were in stage IIa, 1891 (30%) were in stage IIb, 69 (1%) were in stage IIIa, and 3321 (53%) were in stage IIIb. With a median follow-up of 68 months (57-79 months) for the entire group, there was no significant difference in the outcome of 953 patients with international federation of gynecology and obstetrics (FIGO) Ib-IIa treated after radical surgery, pre-operative radiation therapy (pre-op RT) + Sx or after radical radiation; their disease-free survival (DFS) was 60-62% at 8 years. In our series of 1891 patients with stage IIb and 3321 with stage IIIb, a respective DFS of 56% and 40% was achieved at 8 years. Over the last two decades, with the acquisition of newer facilities and inception of Joint Clinics, there has been a significant refinement in the treatment protocols and outcome. Improving radiation strategies to improve therapeutic ratio is the key to success.

Molecular and Circulatory Expression of Insulin Growth Factors in Indian Females with Advanced Cervical Cancer

Recent studies have demonstrated an association between insulin growth factor (IGF) and insulin growth factor binding protein-3 (IGFBP-III) serum levels and increased risk for various cancers. However, little information is available on clinical implications of the IGF system in Indian patients with cervical cancer. This study explored associations by analyzing their expression profiles in cervical cancer cases. Totals of 50 patients with advanced cervical cancer and 40 healthy controls were enrolled. Human papillomavirus (HPV) and cervical biopsy sample were obtained from all participating women. Circulatory levels were estimated by ELISA and the tissue expression was assessed using RT-PCR and Western blotting. Levels of IGF-I and II showed significant increase whereas IGFBP-III showed significant decline in all patients as compared to controls. Spearman correlation analysis between IGFs and HPV status showed significant correlations. We demonstrated elevated circulating levels and tissue expression of IGF-I and IGF-II in advancer cancer cervix patients, as compared with controls, with a converse trend being apparent for IGFBP-III. In future, associations of the IGF system and clinical outcome of cervical cancer patients in post treatment samples might point to significance in disease mapping as a prognostic marker after validation with a larger patient series.

Adaptive image guided brachytherapy for cervical cancer: A combined MRI-/CT-planning technique with MRI only at first fraction

PurposeTo investigate and test the feasibility of adaptive 3D image based BT planning for cervix cancer patients in settings with limited access to MRI, using a combination of MRI for the first BT fraction and planning of subsequent fractions on CT. Material and methodsFor 20 patients treated with EBRT and HDR BT with tandem/ring applicators two sets of treatment plans were compared. Scenario one is based on the “gold standard” with individual MRI-based treatment plans (applicator reconstruction, target contouring and dose optimization) for two BT applications with two fractions each. Scenario two is based on one initial MRI acquisition with an applicator in place for the planning of the two fractions of the first BT application and reuse of the target contour delineated on MRI for subsequent planning of the second application on CT. Transfer of the target from MRI of the first application to the CT of the second one was accomplished by use of an automatic applicator-based image registration procedure. Individual dose optimization of the second BT application was based on the transferred MRI target volume and OAR structures delineated on CT.DVH parameters were calculated for transferred target structures (virtual dose from MRI/CT plan) and CT-based OAR.The quality of the MRI/CT combination method was investigated by evaluating the CT-based dose distributions on MRI-based target and OAR contours of the same application (real dose from MRI/CT plan). ResultsThe mean difference between the MRI based target volumes (HR CTVMRI2) and the structures transferred from MRI to CT (HR CTVCT2) was −1.7±6.6cm3 (−2.9±20.4%) with a median of −0.7cm3.The mean difference between the virtual and the real total D90, based on the MRI/CT combination technique was −1.5±4.3Gy EQD2. This indicates a small systematic underestimation of the real D90. ConclusionsA combination of MRI for first fraction and subsequent CT based planning is feasible and easy when automatic applicator-based image registration and target transfer are technically available. The results show striking similarity to fully MRI-based planning in cases of small tumours and intracavitary applications, both in terms of HR CTV coverage and respecting of OAR dose limits. For larger tumours and complex applications, as well as situations with unfavourable OAR topography, especially for the sigmoid, MRI based adaptive BT planning remains the superior method.

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.

Impact of dosimetric and clinical parameters on clinical side effects in cervix cancer patients treated with 3D pulse-dose-rate intracavitary brachytherapy

Background and purposeTo assess the association between dosimetric/clinical parameters and gastrointestinal/urinary grade 2–4 side effects in cervix cancer patients treated with 3D pulse dose rate brachytherapy. Materials and methodsThree hundred and fifty-two patients received brachytherapy associated with external-beam radiotherapy (EBRT) for 266 of them; 236 patients underwent surgery. The doses for the most exposed 2, and 0.1cm3 (D2cc and D0.1cc) volumes of the rectum and bladder as well as bladder ICRU point dose (DICRU) were converted into isoeffective doses in 2-Gy fractions. The clinical parameters analyzed were: age, smoking habits, arteritis, diabetes, previous pelvic surgery, FIGO stage, nodal status, pathology, pelvic surgery, EBRT and chemotherapy. Side effects were prospectively assessed using the CTCAEv3.0. Cutoff dose levels were defined separately for patients treated with EBRT and brachytherapy (Group 1) and with preoperative brachytherapy (Group 2). ResultsThe median follow-up was 23.4months. In Group 1 a significant predictive value of rectum D0.1cc and D2cc, bladder D0.1cc and DICRU for gastrointestinal and urinary toxicity was found using as cutoff 83, 68, 109 and 68Gyα/β3. In Group 2 a significant predictive value of bladder D0.1cc, D2cc and DICRU for urinary toxicity was found using as cutoff 141, 91 and 67Gyα/β3, but not for the rectum D0.1cc and D2cc; smoking had a significant predictive value on urinary toxicity. ConclusionsFor patients treated with brachytherapy and EBRT, rectum D0.1cc and D2cc and bladder D0.1cc and DICRU had a predictive value for toxicity. For patients treated with preoperative brachytherapy, bladder D0.1cc, D2cc and DICRU and smoking had a predictive value for urinary toxicity.

Evaluation of the overall survival rates in locally advanced cervix cancer patients treated with radiotherapy alone and chemoradiation: A Brazilian experience.

e15509 Background: Locally advanced cervical cancer is a major worldwide health problem. The treatment might include radiotherapy and few trials evaluate the timing of pelvic external irradiation (RT) and high dose rate brachytherapy (HDR) in local control and survival rates of these patients as well as the addition of chemotherapy. The objective were to evaluate the overall survival rates in locally advanced cervix cancer patients and determine the clinical and treatment prognostic factors for local control and overall survival rates. Methods: A retrospective cohort study was carried out with 261 patients stage IIIB, 164 patients received 54 Gy RT to the pelvis and 30 Gy HDR without chemotherapy and 97 patients received 54 Gy RT to the pelvis and 30 Gy HDR with weekly cisplatin 40mg/m2 IV (CDDP) from August 1998 to June 2004 in Hospital Haroldo Juacaba, a Brazilian northeastern hospital. The mean follow-up time was 50 months (2-185 months) and the Kaplan-Meier method was used to calculate survival curves. The Cox regression was used to evaluate multivariate analysis and p values =&lt;0.05 was considered significant. Results: Local control and 5-year survival rates were 39.6% and 38.4% for exclusively radiation and 50.5% and 47.4% for chemoradiation (p = 0.19 and p = 0.36, respectively). The mean treatment time was 61 days. Both local control and overall survival rates were affected by age, parametrial involvement and the timing of brachytherapy (p&lt;0.05). The overall treatment time did not influence survival or local control rates (p&gt;0.05). But less than six cycles of chemotherapy improved local control rates better than six or more cycles (55.1% versus 44.9% p = 0.02). Conclusions: The study is a nonsuperiority one where the addition of weekly chemotherapy with six cycles of CDDP 40mg/m2 during the irradiation did not improve overall survival rates. Further prospective studies would be useful to evaluate the benefit of adding weekly chemotherapy to the standard radiotherapy treatment as well as the financial impact of the adoption of this international guideline in patients with advanced lesions from developing countries.

Effect of fenugreek methanolic extract in inducing apoptosis through triggering proapoptotic genes

Fenugreek (Trigonella foenum graecum) is an active constituent of many traditional medicines to alleviate many diseases including cancer, diabetes, high cholesterol, wounds, inflammation, and gastrointestinal ailments. Since, the mechanism of action of several anticancer drugs is based on their ability to induce apoptosis, the objective of the study was sought to characterize the downstream apoptotic genes regulated by fenugreek methanolic extract (FME) in SiHa cells. FME effectively kills SiHa cells through induction of apoptosis. IC50 was recorded at 75μg/mL while apoptosis was confirmed by TUNEL assay and q‐PCR assays. Cells were exposed to 75μg/mL FME for 24 and 48 hours, and apoptosis was found in 26.2% and 35.1% cells respectively. Further, expressions of proapoptotic genes e.g. Caspase 3, 8, 9, p53, Fas, FADD, Bax and Bak were studied by q‐PCR. Caspase 3, 8, 9, p53, Bax and Bak were found to be increased significantly whereas expressions Fas and Fadd did not show any significant changes. In summary, the induction of apoptosis by FCE is affected by its ability to increase the expression of pro‐apoptotic genes such as Caspase 3, 8, 9, p53, Bax and Bak and it holds promise for consideration in complementary therapy in cervix cancer patients under chemotherapeutic interventions upon further investigation.

Challenges of anemia correction during radiotherapy and chemoradiation

The effect of radiotherapy depends on optimal tumour oxygenation, as tumour hypoxia impairs the production of radiation-induced cytotoxic free radicals resulting in less tumour cell kill. The range of haemoglobin levels optimal for tumour oxygenation is 12–14 g/dl in women and 13–15 g/dl in men. It appears reasonable to elevate the haemoglobin level in anaemic cancer patients into this optimal range. This may be achieved with red blood cell transfusions (RBCT) or erythropoiesis stimulating agents (ESAs). However, RBCT have had negligible or even negative effect on patient outcome, possibly because RBCT induce immunosuppression or result in haemoglobin levels too high for optimal tumour oxygenation. Several randomized trials have demonstrated that patients irradiated for head-and-neck cancer had worse outcomes with ESAs than the control group. However, in the majority of these trials, over-treatment with ESAs resulted in haemoglobin levels above the optimal range. Tumour oxygenation is impaired by inappropriately high haemoglobin levels due to increased blood viscosity and decreased tumour cell perfusion. This concept is supported by the findings of prospective studies in cervix cancer and esophageal cancer patients. In these studies the ESA administration was withheld at a haemoglobin level of 14 g/dl resulting in a positive effect of ESAs on treatment outcome. In summary, the effect of RBCT and particularly of ESAs during radiotherapy remains unclear. Further randomized trials are required. Until such trials are available, one should follow the ASCO and ESMO guidelines that are very conservative regarding the administration of ESAs during radiotherapy and chemoradiation.

Biomarkers Expression in Cervical Cancer and High Grade Squamous Intraepithelial Lesions

Objectives: The finding of new prognostic factors in human cervix cancer is necessary to improve present conventional treatments. The aim of the present study was to determine the expression and evaluate the prognostic value of hypoxia-inducible factor-1(HIF-1α), vascular endothelial growth factor (VEGF) and eritropoyetin receptor (EpoR) in cervix cancer stages IIA-IIB and in preinvasive high grade squamous intraepithelial lesions (HSIL) Methods: The study included 70 patients with cervix cancer, FIGO stages IIA-IIB, 28 patients with HSIL and normal cervix (n = 28). HIF-1α, VEGF and EpoR expression were analyzed in tissue samples by immunohistochemistry using commercial antibodies. Expression and overexpression of the tumor markers were quantified according to German Immunoreactive Score. Results: HIF-1α, EpoR and VEGF overexpression was detected in 30%, 37% and 51% of cancer patients respectively. Patients with HSIL showed enhanced expression only of EpoR and VEGF (39.2% and 71.4%) while VEGF was overexpressed in 21% of the specimen. No correlation was found between VEGF and EpoR with disease-free overall survival (OS), tumor recurrences or prognostic factors. Only overexpression of HIF-1 was associated with less median survival measured up to 24 months, unless it was not maintained a long time. Conclusion: Although any of the markers could be considered as independent prognostic factor for cervix cancer patients, our data showed a significant increase in their expression from the premalignant lesion up to the invasive stages of tumor progression.

Abstract PL06-03: Effect of patient navigation on time from definitive diagnosis to initiation of treatment (T2) for breast, prostate, colorectal, and cervical cancers

Abstract Background: Barriers to timely initiation of treatment in newly diagnosed cancer patients may add to cancer health disparities of low income, uninsured and minority populations. Objectives: To conduct a clinical trial to evaluate the impact of patient navigation on the time from cancer diagnosis to initiation of the first treatment in a medically underserved patient population. Methods: Nine sites participated in the National Cancer Institute Patient Navigation Research Program (PNRP) study. 2,107 cancer patients enrolled in the study, 1,033 in the navigated and 1,074 in the control groups. Analysis was on the individual patient level, due to site population heterogeneity. Results: Demographics included 39% Black, 32% White, and 27% Hispanic; 85% female, 15% male. Insurance status included 17% uninsured, 45% public, and 38% private. The navigated and control groups were well balanced for major covariates. Mean and median times from diagnosis to first treatment were not impacted by patient navigation. Treatment patterns did differ in that more mastectomies were performed in the control vs. navigated breast cancer patients (32 vs. 21%), while more cone biopsies (23 vs. 15%) and fewer LEEP procedures (49 vs. 65%) were performed in the control vs. navigated cervix cancer patients. Implications: Patient navigation did not impact the time from cancer diagnosis to start of first treatment in a medically underserved population, while it may have impacted certain patterns of care. Next Steps: We plan further analyses by site and cancer type, assess covariate effects, perform a sensitivity analysis, and assess patient-navigator interactions. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):PL06-03.

Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer

BackgroundTo analyse the overall clinical outcome and benefits by applying protocol based image guided adaptive brachytherapy combined with 3D conformal external beam radiotherapy (EBRT)±chemotherapy (ChT). MethodsTreatment schedule was EBRT with 45–50.4Gy±concomitant cisplatin chemotherapy plus 4×7Gy High Dose Rate (HDR) brachytherapy. Patients were treated in the “protocol period” (2001–2008) with the prospective application of the High Risk CTV concept (D90) and dose volume constraints for organs at risk including biological modelling. Dose volume adaptation was performed with the aim of dose escalation in large tumours (prescribed D90>85Gy), often with inserting additional interstitial needles. Dose volume constraints (D2cc) were 70–75Gy for rectum and sigmoid and 90Gy for bladder.Late morbidity was prospectively scored, using LENT/SOMA Score. Disease outcome and treatment related late morbidity were evaluated and compared using actuarial analysis. FindingsOne hundred and fifty-six consecutive patients (median age 58years) with cervix cancer FIGO stages IB–IVA were treated with definitive radiotherapy in curative intent. Histology was squamous cell cancer in 134 patients (86%), tumour size was >5cm in 103 patients (66%), lymph node involvement in 75 patients (48%). Median follow-up was 42months for all patients.Interstitial techniques were used in addition to intracavitary brachytherapy in 69/156 (44%) patients. Total prescribed mean dose (D90) was 93±13Gy, D2cc 86±17Gy for bladder, 65±9Gy for rectum and 64±9Gy for sigmoid.Complete remission was achieved in 151/156 patients (97%). Overall local control at 3years was 95%; 98% for tumours 2–5cm, and 92% for tumours >5cm (p=0.04), 100% for IB, 96% for IIB, 86% for IIIB. Cancer specific survival at 3years was overall 74%, 83% for tumours 2–5cm, 70% for tumours >5cm, 83% for IB, 84% for IIB, 52% for IIIB. Overall survival at 3years was in total 68%, 72% for tumours 2–5cm, 65% for tumours >5cm, 74% for IB, 78% for IIB, 45% for IIIB.In regard to late morbidity in total 188 grade 1+2 and 11 grade 3+4 late events were observed in 143 patients. G1+2/G3+4 events for bladder were n=32/3, for rectum n=14/5, for bowel (including sigmoid) n=3/0, for vagina n=128/2, respectively. Interpretation3D conformal radiotherapy±chemotherapy plus image (MRI) guided adaptive intracavitary brachytherapy including needle insertion in advanced disease results in local control rates of 95–100% at 3years in limited/favourable (IB/IIB) and 85–90% in large/poor response (IIB/III/IV) cervix cancer patients associated with a moderate rate of treatment related morbidity. Compared to the historical Vienna series there is relative reduction in pelvic recurrence by 65–70% and reduction in major morbidity. The local control improvement seems to have impact on CSS and OS. Prospective clinical multi-centre studies are mandatory to evaluate these challenging mono-institutional findings.