Stage IIB-IIIB Cervical Cancer Research Articles

The controlling nutritional status score as a new prognostic predictor in patients with cervical cancer receiving radiotherapy: a propensity score matching analysis

BackgroundAs assessment tools of nutritional status, the controlling nutritional status (CONUT) and modified controlling nutritional status (mCONUT) score are associated with survival in various cancers. We aimed to investigate the association between the CONUT/mCONUT score’s prognostic value and survival time in patients with FIGO stage IIB–IIIB cervical cancer treated with radiotherapy.MethodsIn this retrospective study, 165 patients between September 2013 and September 2015 were analyzed, and the optimal CONUT/mCONUT score cut-off values were determined using receiver operating characteristic curves. Propensity score matching (PSM) was used to minimize selection bias. The Kaplan–Meier method and a Cox proportional hazard model were used to assess the CONUT/mCONUT score’s predictive value linked to survival time. Two nomograms were created to predict the overall survival (OS) and progression-free survival (PFS).ResultsThe cut-off values for CONUT and mCONUT score were both 2. Five-year OS and PFS rates were higher in a low CONUT score group than in a high CONUT score group (OS: 81.1% vs. 53.8%, respectively, P < 0.001; PFS: 76.4% vs. 48.2%, respectively; P < 0.001). A high CONUT score was associated with decreased OS (hazard ratio (HR) 2.93, 95% CI 1.54–5.56; P = 0.001) and PFS (HR 2.77, 95% CI 1.52–5.04; P < 0.001). High CONUT scores influenced OS in the PSM cohort. A high mCONUT score was not associated with decreased OS and PFS in Cox regression analysis.ConclusionThe CONUT score is a promising indicator for predicting survival in patients with cervical cancer receiving radiotherapy.

Prediction of radiation complications by determining the blood oxidation processes in cervical cancer patients under chemoradiotherapy

Background. Radiotherapy (RT) is one of the principal methods in cancer management, and its administration in oncology practice is much wider nowadays because of the increased incidence of newly diagnosed cancer cases with wide spread and aggressive course of tumor process, and also in view of organ-sparing strategies in the combined treatment. However, the radiation reactions, especially local ones in rectum or bladder, can’t be completely avoided even using the most advanced radiotherapy facilities and dosimetry planning. Therefore, at present time not only technical modernization, but also the progress in radiobiology should be considered. Given the cytotoxic properties of some anticancer drugs, they are used in the combined therapy of cervical cancer (CC) to receive a radiosensitizing effect on the malignant cells. In particular, cisplatin inhibits reparative processes by affecting the enzymes involved in restoring the integrity of DNA or chromosome structure. Administration of the combined radiation and chemotherapy leads not only to an increase in the percentage of tumor regression, but also to an increase in the number of radiation injuries to healthy tissues. Therefore, prediction of such injuries, research and development of means of their prevention and treatment in the regimen of chemoradiotherapy (ChRT) of CC is extremely urgent and remains an unsolved problem to date. Purpose. Development of personalized approaches in ChRT in CC patients by studying its efficiency, assessing its toxicity, and predicting radiation injuries according to the data of blood oxidative processes in patients. Materials and methods. The combined radiotherapy (CRT) and ChRT were administered to the stage IIB–IIIB CC (T2b-3bN0-1M0) patients (n = 105) at the National Cancer Institute. Patients aged 25–75 years were divided into two groups: the study group and the comparison group. Complex clinical examination was conducted prior to treatment featuring the assay of tumor parameters, state of «critical organs». At the stage I of CRT regimen, conformal irradiation on pelvis minor was delivered at the electron linear accelerator «Clinac 2100 CD» with an energy of 6 MeV per area of pelvis minor with single radiation dose (SRD) of 2.0 Gy and total radiation dose (TRD) of up to 46 Gy. Patients in the study group received the CRT along with administration of chemoradiomodifying agent cisplatin 40 mg/m2 once a week intravenously (drip-feed), patients in the comparison group received no radiomodifier. At the stage II of CRT regimen, an intracavitary brachytherapy (ICBT) was administered to the CC patients at the gamma therapy equipment «AGAT-VU» using 60Co (high dose rate – HDR) sources in the mode of SRD of 5 Gy 2 times a week, 7–8 fractions, and TRD of 35–40 Gy at p. A. The TRD in total was 77–89 Gy at the p. A and 54–60 Gy at p. B. Administration of cisplatin 40 mg/m2 at the stage II of CRT was continued in the study group once a week intravenously (drip-feed), total dose of up to 200–300 mg. Radiobiological studies were performed on the peripheral blood samples from the CC patients (n = 39) before and after ChRT. The control group consisted of healthy women of the appropriate age. Blood was sampled into the special 6 ml Vacutainer type tubes with an anticoagulant according to the manufacturer’s instructions (BioReagent). Intensity of generation of О• 2– in PBL was evaluated by the chemiluminescence method using the lucigenin indicator, which, as a result of reacting with О• 2–, emits light quanta recorded by the device. Measurements were carried out on the AutoLumat LB 953 device (Germany) with appropriate corrections made to the methodology. Results and discussion. Effectiveness of CRT in CC patients was evaluated according to regression of the primary tumor focus (clinical, ultrasound, MRI or SCT data) and presence/absence of toxic manifestations of treatment following the criteria for evaluating the solid tumors regression according to the Response Evaluation Criteria in Solid Tumor (RECIST). Conclusions. The results of the study indicate that chemoradiotherapy contributes to pronounced regression of cervical tumors and does not increase toxicity of treatment due to timely correction of complications.

Comparing dosimetric and cancer control outcomes after intensity-modulated radiation therapy and tomotherapy for advanced cervical cancer.

Concurrent chemoradiation therapy (CCRT) is the standard treatment for locally advanced cervical cancer. The present study aimed to compare the therapeutic responses, toxicities and dosimetric parameters between intensity-modulated radiation therapy (IMRT) and tomotherapy (TOMO) in patients with advanced cervical cancer. This retrospective study included 310 patients with stage IIB-IIIB cervical cancer who underwent CCRT, with 155 patients in each group. Intracavitary brachytherapy was performed after a course of external beam radiation therapy (EBRT), or in the last week of pelvic EBRT. The treatment planning aim at point A (defined as a reference location 2 cm above the vaginal fornix and 2 cm beside the mid axis of the uterus) was >85 Gy in an equivalent dose at 2 Gy. There was no statistical difference with regard to clinicopathological characteristics between the two groups (P>0.05). Improved dose conformity and dose homogeneity (P<0.05) were observed in TOMO planning. TOMO provided more efficacious critical organ sparing than IMRT when assessing the percentage of normal tissue receiving at least 20 Gy (V20) for the bladder, the percentage of normal tissue receiving at least 40 Gy (V40) for the femoral head, and the V40 and V20 for the rectum (P<0.05). TOMO demonstrated a greater ability to protect the ovary (P<0.05). The acute radiation toxicity of proctitis and leukopenia were significantly lower in the TOMO group (P<0.05). The chronic radiation toxicity of radiation enterocolitis and cystitis was lower in the TOMO group (P<0.05). Thus, TOMO provided better critical organ sparing than IMRT. The radiation toxicities were acceptable. Therefore, TOMO appears to be a good option for the treatment of stage IIB-IIIB cervical cancer.

Expression of Bax Protein as A Prognosis Factor of Radiotherapy Response to Decreased Tumor Size in Stage IIB-IIIB Cervical Cancer

Background: Cervical cancer plays a role as the leading cause of cancer death for women in developing countries. Radiation therapy kills cancer cells through double strand breaks and the apoptotic process. Bax protein is one of the regulators of apoptosis. This study analyzed the role of Bax expression as a prognostic factor in radiation therapy response in reducing tumor size in patients with advanced cervical cancer (IIB-IIIB). Subjects and Method: This research is a retrospective cohort observational analytic study from January 2021 to April 2021 in the Department of Obstetrics and Gynecology in collaboration with the Department of Anatomical Pathology, Dr. Moewardi Hospital, Surakarta, Indonesia. This study involved 30 cervical cancer stage IIB-IIIB patients. The level of Bax expression was determined by immunohistochemical examination. ROC curve analysis was used to find cut-off points and evaluate the sensitivity and specificity of Bax in the prognosis of radiotherapy in patients with advanced cervical cancer (IIB-IIIB). Chi square test was used to determine the relationship between Bax expression and changes in tumor size in cervical cancer patients. Results: The ROC curve analysis showed that the AUC Bax score in prognosis of radiation therapy was 0.575 (CI 95%= 0.32 to 0.83) and the cutoff point was 62.5%. Based on the analysis of the ROC curve, the Bax expression of 62.5% shows a sensitivity of 56.5% and a specificity of 71.4%. Analysis of the relationship between Bax protein expression on changes in tumor size using the Chi Square test showed a P value of 0.390 (p&gt; 0.05). Conclusion: The expression of Bax protein cannot play a role as a prognostic factor in the response of radiation therapy to the reduction in tumor size in stage IIB-IIIB uterine cervical cancer.

Impact of different treatment plans on EQD2 for intracavitary brachytherapy of cervical cancer

BackgroundCancer is one of the leading causes of death worldwide. According to GLOBOCAN estimates, there were 341,831 deaths from cervical cancer in 185 countries in 2020. The aim of this study was to compare equieffective dose (EQD2) at 2 Gy per fraction by using dose volume histograms (DVHs) derived from external beam radiotherapy (EBRT) and high-dose rate brachytherapy (HDR-BRT) treatment plans used in cervical cancer radiotherapy.MethodsFifteen patients with stage IIB-IIIB cervical cancer were included in this retrospective study. Treatment with three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) was planned for all patients in 28 fractions, with a total of 50.4 Gy to be delivered to the whole pelvic region. After EBRT, manual optimization (MO) or inverse optimization (IO) HDR-BRT plans were created in 4 fractions with a total of 28 Gy. The plans obtained were grouped as IMRT + IO, IMRT + MO, 3DCRT + IO, and 3DCRT + MO by calculating EQD2s among these plans. D90, D95, and D98 values were compared in all plans for CTVHR total EQD2. In addition, EQD2 values ​for critical organs at risk (OARs) such as rectum, bladder, small intestine, and sigmoid were compared in all plans for volumes of 2 cm3, 1 cm3, and 0.1 cm3, respectively.ResultsThere was no significant difference between the treatment groups in terms of CTVHR D90 and CTVIR D90 values; However, CTVHR D95 (p = 0.000) and CTVHR D98 (p = 0.000) values ​were found to be better in IMRT + IO technique. The IMRT + IO technique provided better protection for 2 cm3, 1 cm3, and 0.1 cm3 volumes of OARs compared to other techniques.ConclusionsConsidering all parameters such as CTVHR, CTVIR, rectum, bladder, small intestine, and sigmoid, combination of IMRT + IO treatment option was found to be significantly superior in total EQD2 calculations compared to other plans.

Laparoscopic retroperitoneal para-aortic lymph node biopsy in advanced cervical cancer with pelvic lymph node metastases: A single-center prospective study.

Extended-field concurrent chemoradiation therapy (Ex-CCRT) has been widely used for para-aortic lymph node (PAN) metastases confirmed by radiographic assessment without surgical exploration. The objective of this prospective study was to evaluate the clinical value of laparoscopic retroperitoneal PAN biopsy in locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastases. From May 2017 to March 2020, stage IIB-IIIB cervical cancer patients who were diagnosed with PLN metastasis using positron emission tomography-computed tomography (PET-CT) with maximum standardized uptake value (SUVmax) ≥2.0 underwent laparoscopic retroperitoneal PAN biopsy. The radiation fields were extended to PAN areas with pathological metastases. Fourteen patients were diagnosed with cervical squamous cell carcinoma of the International Federation of Gynecology and Obstetrics (FIGO) stage IIB (n=7) and IIIB (n=7). The median operating time was 138 min (range, 104-184 min). The median number of harvested PANs was 19 (range, 6-36). Three patients were positive for PAN metastasis on histological analysis. In this study, the sensitivity and specificity of PET-CT were 66.7% and 90.9%, respectively. Our study is characterized by the use of more appropriate eligibility criteria for LACC with PLN metastases. Our results revealed that laparoscopic retroperitoneal PAN biopsy may be a useful approach to determine the radiation field for PANs during standard radiotherapy planning.

Study of Glutathione-s-transferase and Reduced Glutathione Receiving Chemotherapy

Cervical cancer is the third most prevalent cancer in women worldwide, and the fourth leading cause of death from cancer in women. Recent advances, such as the availability of broad scale genome data, articulated gene tag (EST) data bases, innovative sequence alignment techniques, and X-ray crystallography determination of three-dimensional structures, have significantly expanded our understanding of structure–function relationships in this important enzyme superfamily. Total 36 histologically confirmed patients, locally advanced FIGO stage IIB–IIIB cervical cancer were enrolled. Based on the findings of our research, it can be concluded that improvements in GSH concentration during the treatment of locally advanced cervical cancer can have a major impact on the treatment response. In comparison to the lack of concentration changes in the blood serum of patients who have had no reaction to medication or who have had a reported relapse following treatment, GSH tends to be an effective indicator.

Clinical outcomes observation in stage IIB\u2013IIIB cervical cancer treated by adjuvant surgery following concurrent chemoradiotherapy

BackgroundTo explore the feasibility of adjuvant surgery following concurrent chemoradiation therapy (CCRT) in stage IIB–IIIB (according to FIGO staging of 2009) cervical cancer and analyze risk factors of recurrence after surgery.MethodsForty-nine patients diagnosed with stage IIB–IIIB cervical cancer were reviewed retrospectively. We investigated the risk factors of recurrence after surgery using Chi-squared Test and further analyzed multiple factors affecting postoperative recurrence using the multi-factor logistic regression. Furthermore, the correlation of surgery outcomes (including operation time, bleeding, and hospitalization date and surgery complications) with the time which carried out between CCRT and completion surgery was analyzed.ResultsTumor histology and residual tumor in the cervix were significantly associated with postoperative recurrence (P = 0.014 and P = 0.040, respectively). Logistic regression analysis demonstrated that the independent risk factors of postoperative recurrence were age and residual tumor in the cervix (P = 0.017 and P = 0.030, respectively). Complications (operation time, bleeding, hospitalization date) were compared between patients with an interval with radiotherapy less than 6 weeks and patients with an interval longer than 6 weeks. There were statistical differences in the amount of bleeding and postoperative complications between the two groups (P = 0.019 and P = 0.044, respectively).ConclusionCCRT combined with surgery for stage IIB–IIIB cervical cancer was feasible, reduced the rate of postoperative recurrence and surgery complications were tolerated.

Cost-Effectiveness Analysis of Chemoradiation and Radiotherapy Treatment for Stage IIB and IIIB Cervical Cancer Patients.

PurposeCervical cancer is the second most common type of cancer and cause of death from cancer in Indonesia. In 2013, cervical cancer was the most prevalent cancer in Indonesia, with a rate of 0.8 per 1000 women. Based on the National Guidelines for Cervical Cancer Medical Services in Indonesia, the recommended therapy for stages IIB-IIIB cervical cancer is chemoradiation or radiotherapy. This study aimed to evaluate the cost-effectiveness of chemoradiation and radiotherapy for treating stage IIB-IIIB cervical cancer in a national referral hospital in Indonesia.Patients and MethodsA cross-sectional study from a healthcare perspective using retrospective patient data was conducted. The included patients had stage IIB-IIIB registered cervical cancer, were in the hospital between January 1, 2015 and December 31, 2017, received chemoradiation or radiotherapy, were ≥18 years old, and had complete clinical data and detailed cost of therapy data. The incremental cost-effectiveness ratio (ICER) were calculated, and a sensitivity analysis was performed.ResultsThe average treatment cost per patient was $2944 and $3231 for radiotherapy and chemoradiation, respectively. Despite the fact that the treatment effectiveness of chemoradiation (69.1%) was considered to be higher than that of radiotherapy (63.2%), chemoradiation had more potential side effects than radiotherapy. In a comparison with radiotherapy, the ICER of chemoradiation was $48.6 per complete response rate. Additionally, the cost of radiotherapy was the most influential parameter impacting the ICER.ConclusionChemoradiation was considered to be more costly than radiotherapy. Additionally, the effectiveness of chemoradiation was higher than that of radiotherapy. A cost utility analysis (CUA) is required for further investigation.

Efficacy and Safety of Image-Guided Intensity-Modulated Radiation Therapy and Volumetric Modulated Arc Therapy Combined with Paclitaxel Liposomes and Cisplatin for Locally Advanced Stage IIB-IIIB Cervical Cancer: A Retrospective Study at a Single Center.

BackgroundThis retrospective study aimed to investigate the efficacy and safety of image-guided intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) combined with administration of paclitaxel liposomes and cisplatin for locally advanced stage IIB–IIIB cervical cancer at a single center in China.Material/MethodsThe clinical data of 126 patients with stage IIB–IIIB cervical cancer treated in our hospital were retrospectively analyzed. The patients were divided into the IMRT group (n=63) and the VMAT group (n=63). The short-term clinical efficacy, the incidence of adverse reactions, the quality-of-life score, and the changes in levels of T-lymphocyte subsets, serum inflammatory factors, and tumor markers were compared pre- and posttreatment between the 2 groups.ResultsThe clinical response rate was 90.5% and 96.8% in the IMRT group and the VMAT group, respectively; the difference was not statistically significant. After treatment, the levels of CD3+, CD4+, and CD4+/CD8+ subsets rose significantly, while the CD8+ level declined significantly in both groups compared with the pretreatment levels. After treatment, the levels of serum vascular endothelial growth factor, squamous cell carcinoma antigen, interleukin-8, tumor necrosis factor-α, carcinoembryonic antigen, and carbohydrate antigen 125 declined in both groups compared with pretreatment levels. After treatment, the Karnofsky performance scale score rose in both groups, and it was higher in the VMAT group than in the IMRT group.ConclusionsIMRT and VMAT combined with paclitaxel liposomes and cisplatin have similar short-term clinical efficacy and long-term survival rates in the treatment of stage IIB–IIIB cervical cancer.

Expression of HIF-1α is a predictive marker of the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer.

Platinum-based, arterial infusion chemotherapy as a neoadjuvant chemotherapy (NACT) followed by hysterectomy may be efficient for the treatment of locally advanced cervical cancer and improve prognosis. It is important to predict whether the NACT would be effective before it is launched. Hypoxia inducible factor-1α (HIF-1α) is the master transcriptional regulator of the cellular response to altered oxygen concentration. HIF-1α protein expression is elevated in numerous human malignancies, contributes to poor disease outcome, and has been reported to induce tumorigenesis and chemoresistance. In the present study, patients with International Federation of Gynecology and Obstetrics stage IIB-IIIB cervical cancer (n=59) between 2008 and 2014 were assessed for HIF-1α expression by immunohistochemistry. Tumor samples were obtained by biopsy before any treatment. A double-path chemotherapy regimen, paclitaxel (intravenous) plus cisplatin (intra-arterial injection into the uterine region), was used as NACT. The patients were then separated into two groups according to NACT response: One group comprised patients with NACT, for whom the response to treatment was efficient resulting in complete/partial remission of the tumor (CR + PR group; n=52), the other group contained patients with NACT, for whom the result of the treatment was a stable/progressive disease (SD + PD group; n=7). HIF-1α expression was tested in paraffin-embedded sections using immunohistochemistry. HIF-1α expression was significantly higher in the SD + PD group compared with the CR + PR group (P=0.029). The overall survival time was significantly longer in the CR + PR group compared with the SD + PD group (P<0.001). When the patients were divided into two groups based on HIF-1α expression levels. Low (weighted score ≤4, n=39) and high (weighted score ≥6, n=20) expression level groups; the low HIF-1α expression group was significantly more susceptible to NACT treatment (P=0.025). Cox hazard analysis revealed that a high level of HIF-1α expression and lymph node metastases were significant independent predictors of poor overall survival (P=0.025, HR=6.354; P=0.020, HR=6.909, respectively). These results indicated that the expression of HIF-1α may be able to predict the efficiency of NACT and may be considered an independent prognostic factor for stage IIB-IIIB cervical cancer.

Treatment of locally advanced carcinoma cervix with special emphasis on brachytherapy: A practice pattern survey among young radiation oncologist of India.

Background:Carcinoma cervix is one of the two most common cancers of Indian women with very high morbidity and mortality burden. Although India probably is the leading country in numbers patients of cervix treated radically with combination of teletherapy and brachytherapy (BT), there is presumed diversity of practice across the country due to the inequality of available infrastructure, absence of uniform the training of the radiation oncologists, and absence of any national guidelines. The present survey was conducted to determine current practice patterns in management of locally advanced carcinoma cervix with regard to gynecologic high-dose-rate among the radiation oncologist across the country.Methodology:A 25-item survey was undertaken to study the standard management pattern of Stage IIB–IIIB cervical cancer with special emphasis on the BT practice patterns among various young radiation oncologist working across the country. The survey was undertaken in person in the form of interview questionnaire among the younger members of association of radiation oncologist of India during two national conferences, along with telephonic interview of other members as obtained from the national directory.Results:About 57 young radiation oncologists from 57 centers across the country were surveyed. 25 of them represented private nonacademic centers, 24 represented government academic centers, the rest were from private academic, nongovernmental organization (NGO) run and other centers. The most common teletherapy dose prescribed was 46 Gy/23# for Stage II, and50 Gy/25 # for Stage III disease. HDR after loader with 192Ir is the most common machine (82.6%) in use and computed tomography scan is the most commonly (30/57) used imaging for planning. The most common intracavitary dose pattern for all stages was 7 Gy × 3 fractions (30/57s) and 9 Gy × 2 (12/57) fractions. Although in most centers, computed tomography-based delineation of organs at risk is done routinely; however, target volume delineation and dose prescription/optimization for the same is routinely done in handful of centers (5/57). The mean planned dose to Point A for combined external-beam radiation and BT (EQD210) was about 77.5 Gy for Stage IIIB and 72.6 Gy for Stage II disease.Conclusion:Although fractionation patterns may vary, the overall mean dose administered for cervical cancer is similar across the country, which is slightly lower than the recommended doses as per stage by various international guidelines.

Correlation between treatment modality and response to therapy in two histopathological types of cervical cancer

Cervical cancer is the second commonest cancer in Indonesia, with 2,638 cases reported in 2008. Most therapeutic recommendations currently address squamous cell carcinomas, and some studies suggest that adenocarcinomas exhibit poor response to treatment. This study aimed to examine the correlation between the histopathological types of cervical cancer and response to therapy and to compare the responses to different treatment modalities. This cross-sectional study included secondary data of patients diagnosed with stage IIB-IIIB cervical cancer between 2011–2013 at Cipto Mangunkusumo Hospital who underwent radiation and chemoradiation. Of the 163 patients included in this study, 107 presented with squamous cell carcinoma and 56 with adenocarcinoma. No significant differences in response to therapy were observed between the two histopathological types. Moreover, 67.5% patients received radiation only, whereas 32.5% received concurrent chemoradiation therapy using a platinum-based agent. Among those treated with chemoradiation, 98.1% exhibited complete response, whereas only 72.7% of those receiving radiation exhibited complete response. Irrespective of the treatment type, no differences in the response to therapy were observed between patients with squamous cell carcinoma and adenocarcinoma. Moreover, chemoradiation appeared to induce a better response compared with only radiation in all patients.

Strategy and early results of treatment of advanced cervical cancer patients with synchronous cancers observed in PET-CT imaging

The aim of this study was to present strategy and early results of treatment of advanced cervical cancer patients with synchronous cancers observed in PET-CT imaging, treated at the Greater Poland Cancer Center. The study included a group of 200 patients with diagnosed stage IIB-IIIB cervical cancer who received PET-CT for the purpose of radiotherapy treatment planning. Among our study group, four patients (2%) were found to have a synchronous cancer. Two of the cases were diagnosed as breast cancer. However, cancers diagnosed in the other two patients were head and neck malignancies - hypopharyngeal and laryngeal cancer. The choice of an optimal therapeutic approach requires taking into account characteristics of particular malignancies, their stage and histopathology. The whole therapy included radiotherapy of cervical cancer with various combinations of systemic treatment, radiotherapy or surgery of synchronous cancer. According to treatment results, patients diagnosed with breast cancer and hypopharyngeal cancer achieved complete remission of both primary and secondary tumour. Patient diagnosed with laryngeal malignancy, despite achieving complete remission of cervical cancer, finished radiotherapy of the synchronous cancer at a palliative dose. The growing availability of PET-CT and other imaging methods in cancer diagnosis will increase the number of diagnosed synchronous cancers. Second primary cancers are often detected at an early stage, where radical treatment can be performed for both primary and secondary tumour. However, treatment of such complicated clinical cases as synchronous cancers should be carried out by multidisciplinary teams.

Correlation of expression of radiation-induced immediate-early response 5 and Ku70 factor and with the sensitivity and clinical significance of radiosensitivity for cervical cancer

Objective To investigate the expression of radiation-induced immediate-early response 5(IER5) and Ku70 gene before and after radiotherapy in cervical cancer, as well as the relationship between the two genes and their clinical characteristics. Methods Thirty-five cases patients with stage Ⅱb-Ⅲb cervical cancer who had received cisplatin-based concurrent chemoradiotherapy(DDP-CCRT) were registered.Specimens tissues were obtained from the cervical tumors before and after administration of irradiation dose of 2-6 Gy, 10 Gy, 20 Gyand 30 Gy.Western blotting and quantitative polymerase chain reaction(qPCR) method were performed to detect the expression of proteins and mRNA in IER5 and Ku70, respectively.The relationship between IER5 and Ku70 was analyzed. Results The protein and mRNA expression levels of IER5 in cervical cancer patients treated with radiation doses of 10 Gy(0.818±0.678), 20 Gy(0.981±0.734), 30Gy(1.637±0.817) were significantly higher than those before treatment(0.503±0.188, t=2.626, 3.516, 6.919, P<0.01). The expression of IER5 was positively correlated with the radiation dose(r=0.498, P<0.01), increased with the increase of dose.Ku70 proteins at the dose of 30 Gy was higher than those before treatment((0.494±0.304) vs.(0.318±0.098), t=2.239, P<0.05). There was a certain correlation between IER5 and Ku70 before and after radiotherapy(r=0.558, P<0.05; r=0.344, P<0.01). There was a significant interaction between the expression of IER5 in different irradiation dose and the tumor size(F=2.582, P<0.05). Conclusion IER5 may participate in the regulation of DNA damage repair process by interacting with Ku70, so as to affect the sensitivity of cervical cancer radiotherapy.It is possible to predict the sensitivity of radiotherapy through detecting the combined expression of IER5 and Ku70 in cervical cancer. Key words: Radiation-induced immediate-early response 5; Ku70; Cervical cancer; Radiosensitivity; Nnonhomologous end joining

Concurrent pelvic radiation with weekly low-dose cisplatin and gemcitabine as primary treatment of locally advanced cervical cancer: A phase II study

Purpose: This study was done to evaluate response, compliance and survival of weekly low dose cisplatin (20 mg/m 2 ) and gemcitabine (125 mg/m 2 ) concurrently with pelvic radiation as primary treatment of stage IIB-IIIB cervical cancer. Methods: External radiation consisted of 50 Gy/25 fractions using 6-10 MV photon followed by 600 cGy boost to parametrium if it was still felt thickened. Then, intracavitary radiotherapy to deliver 60 Gy at point A. Chemotherapy consisted of gemcitabine at a dose of 125 mg/ m 2 was given by i.v infusion over 30 minutes immediately after cisplatin 20 mg/ m 2 weekly for 5 weeks during EBRT. Forty–five eligible patients received the treatment protocol. Results: Toxicity was tolerable and manageable. No grade 4 toxicity while grade 3 was recorded in hematologic one only. In order of frequency; diarrhea, nausea and vomiting, and anemia (50%, 40%, 35.5%) were most common adverse events. Overall clinical response rate was 93.4% with pathological complete response of 62.2%. After median follow-up of 20 months, 2-year survival and progression-free survival rates were 90.5% and 81% respectively. Conclusion: Weekly combination of low- dose cisplatin and gemcitabine given concurrently with pelvic radiotherapy in primary treatment of locally advanced cervical cancer resulted in a high response rate with a good compliance. Further exploration is needed for the use of this approach prior to incorporating it into routine clinical care through phase III clinical trial.

Robotic radiosurgery as an alternative to brachytherapy for cervical cancer patients

To compare MRI-guided brachytherapy (BT) and two different dose prescriptions for robotic radiosurgery (RRS) in locally advanced cervical cancer. Eleven patients with FIGO stage IIB-IIIB cervical cancer underwent RRS instead of BT for various reasons. A total dose of 30Gy was administered in five fractions. The maximum dose was chosen such that the prescribed dose was 70 % of the maximum dose (RRS70). To simulate BT more closely, additional plan calculations were carried out for a higher maximum dose with the same enclosing dose of 30Gy being now 25 % of the maximum dose (RRS25). BT plans were calculated for the same patients (BTRRS). Finally, the resulting three sets of treatment plans were compared with 38 other patients treated with MRI-guided BT and the same dose prescription (BTref). Plan comparisons were performed based on DVH parameters with regard to target coverage (V100), conformation number (CN), and sparing of the organs at risk (OARs). The best coverage of V100 = 100 ± 0 % was obtained with RRS25, followed by RRS70 with 97.1 ± 2.7 %, BTref with 90.9 ± 8.9 %, and the intraindividual BTRRS with 80.6 ± 6.4 %. The sparing of OARs was associated with D0.1cc, D2cc, and D5cc to the rectum, sigmoid, and bladder walls. OAR doses were compliant with the GEC-ESTRO guidelines and comparable among RRS70, RRS25, BTRRS, and BTref. By contrast, RRS25 could not fulfill these guidelines, exceeding considerably the tolerable dose constraints for the walls of the critical OARs. Despite of the excellent coverage and higher maximum dose, the unacceptably high exposure to the OARs disqualified RRS25 as an alternative for BT in cervical cancer patients. By contrast, RRS70 offered the best protection for the OARs, comparable to BT, and even better target coverage and conformity than BT.

The significance of reduced glutathione and glutathione S-transferase during chemoradiotherapy of locally advanced cervical cancer

Background and objectiveTo determine changes in reduced glutathione (GSH) and glutathione S-transferase (GST) during neoadjuvant chemotherapy followed by concurrent chemoradiation for patients with stage IIB–IIIB cervical cancer, and to evaluate their significance to the efficacy of the treatment. Materials and methodsAccording to the prospective phase II study protocol, 36 patients with stage IIB–IIIB cervical cancer were enrolled. A short course of intensive weekly neoadjuvant cisplatin and gemcitabine chemotherapy followed by concurrent weekly cisplatin and gemcitabine-based chemoradiation was administered. Blood samples for GSH, GST analysis were collected and analyzed before the start of the treatment, after neoadjuvant chemotherapy, and after the end of the chemoradiation. ResultsA statistically significant increase in the concentration of GSH after neoadjuvant chemotherapy was identified. After chemoradiation, values of this rate significantly decreased in contrast with GSH concentration after neoadjuvant chemotherapy in cases of stage IIB, regional metastases negative patients group, patients with a positive response to treatment, and patients who had no progression of the disease during the first 2 years after treatment. Statistically significant changes in GST during the treatment were not identified; the GST concentration after chemoradiation showed a statistically significant difference in GST concentrations in terms of the progression of the disease and disease without progression. ConclusionsThe results suggest that changes in the concentration of GSH during the treatment of locally advanced cervical cancer might be important for the prediction of the efficacy of the treatment. Statistically significant changes in GST concentration levels during the treatment were not observed.

Study of the radiotherapy modality for patients with stage IIb-IIIb cervical stump cancer

To investigate the radiotherapy modality progress of stageIIb-IIIb cervical stump cancer. The clinical data of 13 patients with stageIIb-IIIb cervical stump cancer undergoing radiotherapy from January 2000 to April 2012 was reviewed. Before 2006, 8 patients received conventional external beam radiotherapy and brachytherapy.Since 2006, 5 patients received intensity-modulated radiotherapy (IMRT) and brachytherapy. The median survival was 12-139 months. The median overall survivals and disease free survivals in the conventional radiotherapy (CRT) group were 57 months and 50 months, 3 cases of them recurred during 8-19 months and died of tumor progression.While, the median overall survivals and disease free survival in the IMRT group both were 21 months and nobody recurred. In the CRT group, 7 patients suffered toxicities, including 5 patients grade I-II acute rectum reaction, 2 patients grade I bladder reaction; and 3 had grade I-III, late rectum reaction, 2 patients for grade II bladder late reaction.In the IMRT group, toxicities including 1 case grade I acute or late rectum reaction, and no bladder reaction. In our experience, the recommended IMRT and interstitial brachytherapy for the selected patients with advanced cervical stump carcinoma may be obtain better tumor dose distribution and more sparing of the organ at risk.

Brachytherapy-emulating robotic radiosurgery in patients with cervical carcinoma

PurposeTo evaluate the technique, dosimetry, dose-volume-histograms (DVHs) and acute toxicity for CyberKnife® boost irradiation instead of intra-cervical brachytherapy in patients with cervical cancer.Methods and materialsEleven who were not suitable for brachytherapy with FIGO stage IIB-IIIB cervical cancer underwent primary chemoradiation. After fiducial implantation, T2 contrast-enhanced planning MRI and CT scans at 2-mm slice thickness were collected in the treatment position. The clinical target volume was defined as cervix + macroscopic residual tumour on MRI. Five fractions of 6 Gy each were prescribed to the target volume with a covering single dose 6 Gy. DVH parameters were evaluated for the target and organs at risk. Acute toxicity was documented once a week.ResultsDmeanPTV ranged from 33.6-40 Gy, median 36.7 Gy with a coverage of the PTV calculated to 100% of the prescribed dose ranging from 93.0-99.3% (median 97.7%). For the PTV the median CN was 0.78 (range, 0.66 to 0.87) and the median CI was 1.28 (range 1.15 to 1.52). Gastrointestinal (GI) and genitourinary (GU) toxicity was mild. There was no grade 3 or higher GI and GU toxicity. After 6 months of follow up, there were no local recurrences. For the complete treatment, a median EQD2 to 1 cc and 2 cc of the bladder wall was 98.8 Gy and 87.1 Gy, respectively. Median EQD2 to 1 cc and 2 cc of the rectal wall was 72.3 Gy and 64 Gy, respectively, correlating with a risk < 10% for Grade 2–4 late toxicity.ConclusionsCyberKnife robotic radiosurgery in patients with cervical cancer provides excellent target coverage with steep dose gradients toward normal tissues and safe DVH parameters for bladder, rectum and sigmoid. Acute toxicity was mild. Longer follow-up is needed to evaluate the oncological equality.