Treatment Of Advanced Cervical Cancer Research Articles

Clinical effect of concurrent radiotherapy and chemotherapy in the treatment of 60 patients with advanced cervical cancer

Objective To explore the clinical effect of concurrent radiotherapy and chemotherapy in the treatment of advanced cervical cancer. Methods From January 2010 to January 2011, sixty patients with cervical cancer in Taizhou Cancer Hospital were randomly divided into two groups, with 30 cases in each group.The control group was given radiotherapy alone, the observation group was given concurrent radiotherapy and chemotherapy.The adverse reaction, curative effect, long-term effect of 5-year follow-up were compared between the two groups. Results The total effective rate of the observation group was 93.33%, which was significantly higher than 73.33% of the control group, the difference was statistically significant(χ2=14.397, P 0.05). Conclusion The efficacy of concurrent radiotherapy and chemotherapy for patients with advanced cervical cancer is better, and the survival rate of patients with advanced cervical cancer is better. Key words: Uterine cervical neoplasms; Radiotherapy planning, computer-assisted; Chemotherapy, adjuvant

Abstract 2317: Palbociclib monotherapy exhibits potent activity in cervical cancer cell lines

Abstract Background: Over the last decades, little progress has been made in the systemic treatment of patients with advanced or recurrent cervical cancer. We recently performed an silico analysis to identify potential driver pathways of cervical carcinogenesis and candidate targets for treatment.1 Expression2Kinases (E2K) analysis revealed a protein-protein interaction (PPI) network of 162 nodes (including 20 druggable kinases) consisting of 5 signaling modules associated with MYC signaling (module 1), cell cycle deregulation and cyclin signaling (module 2), TGFβ-signaling (module 3), a PI3K - MAPK signaling (module 4) and chromatine modeling (module 5). Methods: The cervical cancer cell lines included in the study were CaSki, SiHa and HeLa. Cells were incubated for 24 or 72 hours with the PI3K pathway inhibitor BYL719 (Novartis), the multiple pathway inhibitor INC280 (inhibits cMET-dependent PI3K and RAS signaling, Novartis), or the CDK4/6 inhibitor PD-0332991 (palbociclib, Selleck Chemicals) in monotherapy. Sensitivity to drug treatment (0 - 10 μM) was investigated using the colorimetric sulforhodamine B (SRB) assay. IC50 values were calculated using WinNonlin Software. Results: Incubation with BYL719 or INC280 for 24 or 72 hours in concentrations up to 10 μM was not able to establish a distinct cytotoxic effect in the three cervical cancer cell lines included in the study. Incubation with 10 μM BYL719 for 72h resulted in only 20% cell kill, while 10 μM INC280 for 72h caused around 30% cell kill in all three cell lines. However, incubation with palbociclib for 72 hours clearly induced a concentration-dependent cytotoxic effect, with IC50 values of 5.32 ± 0.03 μM, 7.69 ± 0.02 μM and 5.68 ± 0.12 μM for HeLa, SiHa and CaSki cells, respectively. Conclusion: CDK4/6 inhibition seems effective in cervical cancer cell lines and should be further evaluated alone and in combination with chemotherapy for the treatment of advanced and recurrent cervical cancer.

Definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) for advanced cervical esophageal cancer.

Recently, definitive chemoradiotherapy (dCRT) has become one of the essential treatment strategies for esophageal squamous cell carcinoma (ESCC) and has been especially gaining prevalence for cervical ESCC to preserve the larynx. Our department recently introduced dCRT concomitant with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) for treating advanced cervical ESCC. This study aims to assess the safety and outcomes of DCF-R in patients with advanced cervical ESCC. We retrospectively assessed 11 patients with advanced cervical ESCC (clinical stage: II-IV, including T4b and/or M1 lymph node) who received DCF-R as the first-line treatment between December 2010 and February 2015. Our patient cohort comprised 8 males and 3 females (median age 68years; range 54-76years). The pretreatment clinical stage included stage II (1), stage III (7), and stage IV (3) cases [including 3 patients with T4b (2 trachea and 1 thyroid) and 3 patients with M1 lymph node]. We attained complete response (CR) in 10 patients and stable disease in 1 patient. Of 10 patients with CR, 5 experienced recurrence and 5 continued exhibiting CR. Furthermore, grade 3 or more adverse events included leucopenia (91%), neutropenia (91%), febrile neutropenia (45%), and pharyngeal pain (55%). While the 2-year overall survival rate was 72%, the 2-year recurrent-free survival rate was 64%, respectively. DCF-R treatment for advanced cervical esophageal cancer could be completed by the careful administration; although a strong blood toxicity might occur, this treatment may provide the chance to obtain favorable prognosis with larynx preservation.

Pembrolizumab treatment of advanced cervical cancer: Updated results from the phase 2 KEYNOTE-158 study.

5522Background: The KEYNOTE-158 study (NCT02628067) is a phase II basket study investigating the antitumor activity of pembrolizumab, an IgG4 anti-PD-1 monoclonal antibody, in 11 cancer types. An u...

Clinical study of intensity-modulated radiation therapy combined with chemotherapy in advanced cervical cancer

Objective To explore the clinical efficacy of intensity-modulated radiotherapy combined with chemotherapy in the treatment of advanced cervical cancer. Methods All 121 patients with advanced cervical cancer (stage ⅡB & ⅢA & ⅢB) selected in our hospital from June 2012 to June 2014, who were treated with combined chemoradiotherapy, were divided into observation group [intensity modulated radiation therapy (IMRT)group)] and control group [3-dimensional conformal radiation therapy (3D-CRT) group]. There was no significant difference between two groups in mean age, body mass index, International Federation of Gynecology and Obstetrics (FIGO) clinical stage, pathological type and chemotherapy mode (P>0.05). The clinical features of two groups were compared. The treatment and follow-up of two groups were recorded. Results The bone marrow suppression [32.2%(19/59) vs 51.6%(32/62)], gastrointestinal reaction [42.4%(25/59) vs 62.9%(39/62)], and rectal reaction rate [27.1%(16/59) vs 45.2%(28/62)] of the observation group were significantly less than that of the control group (P 0.05). Two groups were followed up for 3 years, the local control rate of the observation group was significantly higher than that of the control group (86.3% vs 70.1%) (P<0.05). Conclusions IMRT combined with chemotherapy in the treatment of advanced cervical cancer can improve the local control rate of tumor, protect the endangered organ, and reduce the side effects of radiotherapy. Key words: Uterine cervical neoplasms/DT/RT; Cisplatin/AD; Radiotherapy, intensity-modulated; Combined modality therapy

Therapeutic effects of β-elemene via attenuation of the Wnt/β-catenin signaling pathway in cervical cancer cells.

Concurrent radio chemotherapy treatment prolongs the survival rate of patients with advanced cervical cancer; however, it has adverse side-effects. β-elemene, an active component of the traditional Chinese medicinal herb Curcuma zedoaria, is a promising alternative therapeutic drug for the treatment of advanced cervical cancer. The aim of the present study was to investigate the antitumor effects of β-elemene in human cervical cancer SiHa cells and to determine its underlying therapeutic molecular mechanisms. Cell viability, cell cycle progression and apoptosis were detected using an MTT assay and flow cytometry analysis. Furthermore, the levels of cell migration and cell invasion were investigated using Transwell and wound healing assays. The expression levels of Cyclin-dependent kinase inhibitor 2B (P15), Cyclin D1, cellular tumor antigen p53, apoptosis regulator Bcl-2 (Bcl-2), apoptosis regulator BAX (Bax), 72 kDa type IV collagenase (MMP-2), matrix metalloproteinase-9 (MMP-9), β-catenin, transcription factor 7 (TCF7), and Myc proto-oncogene protein (c-Myc) were analyzed via western blotting. The results revealed that β-elemene inhibited the proliferation of SiHa cells in a dose and time-dependent manner. Administration of β-elemene induced G1 phase cell-cycle arrest, as demonstrated by the upregulation of P15 expression and the downregulation of Cyclin D1 expression. Furthermore, the present study revealed that β-elemene induced apoptosis in SiHa cells by enhancing the expression of p53 and Bax, and suppressing the expression of Bcl-2. In addition, treatment with β-elemene inhibited cell migration and invasion via downregulation of MMP-2 and MMP-9 expression levels. Western blotting demonstrated that β-elemene reduced the expression levels of β-catenin and its downstream target molecule TCF7, thus resulting in reduced levels of their target proteins, including c-Myc, Cyclin D1, Bax and MMP-2 in cervical cancer cells. The results of the present study suggested that β-elemene may inhibit cell proliferation and invasion, in addition to inducing apoptosis, via attenuation of the Wnt/β-catenin signaling pathway in cervical cancer cells.

Radiation or chemoradiation: initial utility study of selected therapy for local advanced stadium cervical cancer

This study aimed to compare radiation only or chemo radiation treatment of local advanced cervical cancers by examining the initial response of tumors and acute side effects. An initial assessment employed value based medicine (VBM) by obtaining utility values for both types of therapy. The incidences of acute lower gastrointestinal, genitourinary, and hematology side effects in patients undergoing chemoradiation did not differ significantly from those undergoing radiation alone. Utility values for patients who underwent radiation alone were higher compared to those who underwent chemoradiation. It was concluded that the complete response of patients who underwent chemoradiation did not differ significantly from those who underwent radiation alone.

Outcome and toxicity of radical radiotherapy or concurrent Chemoradiotherapy for elderly cervical cancer women

BackgroundConcurrent chemoradiotherapy (CCRT) is the standard treatment for local advanced cervical cancer. However, for elderly patients, studies are limited and the outcomes are controversial. We retrospectively analyzed the efficacy and tolerance of radical radiotherapy (RT) or CCRT in elderly cervical cancer patients and performed comparisons between them.MethodsWe retrospectively analyzed the elderly cervical cancer patients (≥70 years old) treated with radical RT or CCRT between January 2006 and December 2014. For external beam radiotherapy, 50Gy in 25 fractions or 50.4Gy in 28 fractions were delivered via 3-dimensional conformal radiation therapy or intensity modulated radiation therapy. High-dose-rate intracavitary brachytherapy was performed with a dose of 30-36Gy in 5–7 fractions to point A. Concurrent chemotherapy regimens included weekly cisplatin and paclitaxel.ResultsSeventy-three patients were eligible for this study. Twenty-one(28.8%) and 52(71.2%) patients suffered with FIGO stage IB-IIA and IIB-IVA disease, respectively. Twenty-four (32.9%) patients received CCRT. The median duration of follow-up was 32.4 months (4.8–118.8 months). The 3-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) were 64.9%, 67.8% and 66.5%, respectively. By multivariate analysis, CCRT was a significant predictive factor of OS(p = 0.023, 95% confidence interval [CI]: 1.172–8.860), CSS(p = 0.031, 95% CI: 1.131–13.908)and DFS(p = 0.045, 95% CI: 1.023 ~ 6.430). The 3-year OS of patients received RT and CCRT were 54.3% and 83.1%, CSS were 56.8% and 87.1%, DFS were 57.6% and 83.3%. There was no treatment related death. Grade 3–4 acute hematological, gastrointestinal and urinary toxicity incidences were 31.5%, 19.1% and 12.3%, respectively. For grade 3–4 chronic gastrointestinal and genitourinary toxicities, the incidences were 4.1% and 2.7%, respectively. Compared with RT, CCRT was related with high grade 3–4 hematological toxicity (16.3% and 62.5% respectively, p < 0.001), respectively. However, acute nonhematological toxicity and chronic toxicity were not significantly different.ConclusionElderly cervical cancer patients could tolerate radical RT and CCRT very well and get a favored survival. Compared with RT, CCRT could improve the survival of elder cervical cancer patients with similar nonhematological toxicity. CCRT should be considered in elderly cervical cancer patients.

Application of thymalfasin in non-operative treatment of cervical cancer

Objective To observe the effect of thymalfasin on non-operative treatment of cervical cancer. Methods Seventy-eight patients with advanced cervical cancer were divided into two groups according to the digital table, each group in 39 cases.The two groups were treated with concurrent chemoradiotherapy. The observation group was given 1.6 mg of thymalfasin subcutaneously each Monday to Friday. While the control group received no additional treatment. And then the two groups were compared in terms of curative effects, adverse reactions, immune states and cellular immune functions. Results The results showed that the differences of curative effects[there were 23 patients in the control group, as compared with 31 patients in the observation group, achieved a complete response(CR), χ2=3.852, P<0.05], adverse reactions(grade Ⅲ or Ⅳ radiation-induced enteritis occurred in 4 patients in the observation group, and 12 patients in the control group, χ2=5.032, P<0.05; Grade Ⅲ or Ⅳ leukopenia occurred in 16 patients in the observation group, and 25 patients in the control group, χ2=4.165, P<0.05; Grade Ⅲ or Ⅳ nausea, vomit occurred in 6 patients in the observation group, and 14 patients in the control group, χ2=4.303, P<0.05), immune states and cellular immune functions between the two groups were significant[the counts of CD3+(t=9.236, P<0.05), CD4+(t=7.445, P<0.05), CD4+ /CD8+ (t=7.445, P<0.05) and NK(t=9.256, P<0.05)] were significantly higher in the observation group after treatment. Conclusion In the treatment of advanced cervical cancer, concurrent chemoradiotherapy combined with thymalfasin can improve the curative effect, reduce the side effects, improve the quality of life and enhance the immunity. Key words: Uterine cervical neoplasms; Antineoplastic combined chemotherapy protocols; Thymalfasin

Cervical cancer cell-derived angiopoietins promote tumor progression.

Metastatic or recurrent cervical cancer has limited treatment options and a high rate of mortality. Although anti-vascular endothelial growth factor drugs have shown great promise as a therapeutic target for treatment of advanced cervical cancer, drug resistance and class-specific side effects negate long-term benefits. The identification of alternative anti-angiogenic factors will be critical for future drug development for advanced or recurrent cervical cancer. In this study, we found that angiopoietins and Tie receptors were highly expressed in cervical cancer cells. Tie-2 expression in tumor cells predicted poorer prognosis. Wound closure assay and Transwell assay showed that upregulated or downregulated Ang-1 and Ang-2 expression promoted or reduced cervical cancer cell lines migration and invasion, respectively. In subcutaneous xenograft models of cervical cancer, downregulation of Ang-1 and Ang-2 attenuated tumor growth. The expression of vimentin and endomucin and microvessel density were all significantly decreased in the siAng-1 group and siAng-2 group relative to the infection control group. Our data support that dual inhibition of Ang-1 and Ang-2 may be an alternative target for anti-angiogenic adjuvant therapy in advanced or recurrent cervical squamous cell cancer.

Pembrolizumab in cervical cancer: latest evidence and clinical usefulness.

Cervical cancer is the fourth most common cause of cancer-related deaths in women worldwide. With the development of detection of precancerous lesions and preventive human papillomavirus (HPV) vaccination program, a survival improvement has been observed in these patients in developed countries, although disparities in accessibility to treatments exist across countries. While early-stage cervical cancer can be curable with surgery, prognosis of patients who recur remains poor, with limited treatment options. In this latter setting, recently, bevacizumab, an antiangiogenic monoclonal antibody targeting vascular endothelial growth factor (VEGF), has been shown to improve overall survival in combination with chemotherapy as compared with chemotherapy alone. No standard treatments exist beyond this treatment regimen. New effective treatments are therefore much needed in this setting. Immunotherapy has represented a breakthrough in recent years in oncology, with antitumor activity reported with immune-checkpoint inhibitors in a variety of tumor types. We discuss here the latest evidence and clinical usefulness of pembrolizumab, anti-PD-1 checkpoint inhibitor, in the treatment of advanced cervical cancer.

Commissioning of applicator-guided stereotactic body radiation therapy boost with high-dose-rate brachytherapy for advanced cervical cancer using radiochromic film dosimetry

PurposeTo describe an EBT3 GAFCHROMIC film-based dosimetry method to be used in commissioning of a combined HDR brachytherapy (HDRB) and stereotactic body radiation therapy (SBRT) boost for treatment of advanced cervical cancer involving extensive residual disease after external beam treatment. Methods and MaterialsA cube phantom was designed to firmly fit an intrauterine tandem applicator and EBT3 radiochromic film pieces. A high-risk clinical target volume (CTVHR, Total) was contoured with an extended arm at one side. The HDRB treatment was planned to cover the proximal CTVHR, Total with 7 Gy and the distal volume, referred to as CTVHR, Distal, was planned by SBRT for dose augmentation. After HDRB treatment delivery, SBRT treatment was delivered within 1 hour by image guidance using the applicator geometry. Intentional 1D and 2D misalignments were introduced to evaluate the effect on target volumes. In addition, effect of film reirradiation at different time gaps and dose levels was evaluated. ResultsFilm dosimetric accuracy, with up to 2 hours gap between irradiations, was shown to be unaffected. A 2%/2 mm gamma analysis between measured and planned doses showed agreement of >99%. Misalignments of more than 2 mm between applicator and SBRT isocenter resulted in suboptimal dose-volume histogram affecting mostly D98% and D90% of CTVHR, Distal. ConclusionsVisualizing how target dose-volume metrics are affected by minor misalignments between SBRT and HDRB dose gradients, in light of achievable phantom-based experimental quality assurance level, encourages the clinical applicability of this technique. Radiochromic film was shown to be a valuable tool to commission procedures combining two different treatment planning systems and modalities with varying dose rates and energy ranges.

Grassroots Partnership to See and Treat Cervical Cancer in Rural Uganda

Abstract 9 Background: In Uganda, cervical cancer is the leading cause of cancer death, affecting 45 in every 100,000 women annually and killing 25 in every 100,000 annually. To effect change, two Canadian registered charities partnered with a Ugandan nongovernmental organization, a university, and the Ministry of Health to develop a novel screening, treatment, and educational training program. The two major goals of our program were to develop a training program for health care providers in southwestern Uganda for visual inspection of the cervix with acetic acid (VIA) and a cryotherapy see and treat model; and to implement the first cervical cancer screening program of its kind in the Kabale region of southwestern Uganda. Methods: Our program was developed in partnership with Mbarara University of Science and Technology, a grass-roots Ugandan community development organization (Kigezi Healthcare Foundation [KIHEFO]), a Canadian charity that is focused on providing medical and dental care and educational training and infrastructure development (Bridge to Health Medical and Dental), and a Canadian charity that is focused on treatment for advanced cervical cancer (Road to Care). Results: Requisite supplies were obtained by Bridge to Health Medical and Dental and left behind with KIHEFO. A partnership was formed between academia, government, and civil society across Canada and Uganda. Over 5 days, 15 Ugandan health care workers were trained in VIA and cryotherapy, and 96 patients were screened for cervical cancer. Six patients were successfully treated for precancerous lesions. One biopsy was sent for pathology review and analysis. Conclusion: Since the pilot program, KIHEFO has conducted two additional cervical cancer screening programs using VIA and the see and treat approach. A new cervical cancer screening and treatment campaign, along with a quality control and educational training refresher, for the original 15 health care providers is planned for February 2017. Funding: Bridge to Health Medical and Dental and Kigezi Healthcare Foundation in partnership with the Ugandan Ministry of Health. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from the authors.

Management of Para-aortic Lymph Node Disease in Patients With Cervical Cancer: What Is the Best Approach?

Cervical cancer remains a prevalent and deadly disease in low-income countries, especially among young and otherwise healthy women. Multimodality treatment has led to a significant improvement in outcomes for patients with locally advanced disease, and this is mainly because of the incorporation of platinum-based chemoradiotherapy in current treatment protocols. However, locally advanced tumors are associated with a greater risk for para-aortic lymph node (PALN) involvement, which is an important adverse prognostic factor. Most staging techniques have low accuracy for detection of disease in this area, which could lead to understaging and undertreatment. Meanwhile, patients with PALN disease are underrepresented in trials addressing the treatment of advanced cervical cancer and a few studies have been directed at this population. The aim of this review is to analyze the current data regarding staging and treatment of cervical cancer with PALN disease to determine which strategy is best when managing these patients.

Association of Hospital Volume With Racial and Ethnic Disparities in Locally Advanced Cervical Cancer Treatment.

To evaluate racial-ethnic disparities in guideline-based care in locally advanced cervical cancer and their relationship to hospital case volume. Using the National Cancer Database, we performed a retrospective cohort study of women diagnosed between 2004 and 2012 with locally advanced squamous or adenocarcinoma of the cervix undergoing definitive primary radiation therapy. The primary outcome was the race-ethnicity-based rates of adherence to the National Comprehensive Cancer Network guideline-based care. The secondary outcome was the effect of guideline-based care on overall survival. Multivariable models and propensity matching were used to compare the hospital risk-adjusted rates of guideline-based adherence and overall survival based on hospital case volume. The final cohort consisted of 16,195 patients. The rate of guideline-based care was 58.4% (95% confidence interval [CI] 57.4-59.4%) for non-Hispanic white, 53% (95% CI 51.4-54.9%) for non-Hispanic black, and 51.5% (95% CI 49.4-53.7%) for Hispanic women (P<.001). From 2004 to 2012, the rate of guideline-based care increased from 49.5% (95% CI 47.1-51.9%) to 59.1% (95% CI 56.9-61.2%) (Ptrend<.001). Based on a propensity score-matched analysis, patients receiving guideline-based care had a lower risk of mortality (adjusted hazard ratio 0.65, 95% CI 0.62-0.68). Compared with low-volume hospitals, the increase in adherence to guideline-based care in high-volume hospitals was 48-63% for non-Hispanic white, 47-53% for non-Hispanic black, and 41-54% for Hispanic women. Racial and ethnic disparities in the delivery of guideline-based care are the highest in high-volume hospitals. Guideline-based care in locally advanced cervical cancer is associated with improved survival.

Efficacy and toxicity of different concurrent chemoradiotherapy regimens in the treatment of advanced cervical cancer: A network meta-analysis.

The aim of this study was to compare the efficacy and toxicity of different concurrent chemoradiotherapy (CCRT) regimens in the treatment of advanced cervical cancer (CC) by adopting a network meta-analysis. We searched PubMed and Cochrane Library from the inception of these databases to September 2016, and all cohort studies (CSs) related to different CCRT regimens in the treatment of CC were included. A network analysis was adopted to compare the combination of direct and indirect evidence, to analyze the odds ratio (OR), and to draw a surface under the cumulative ranking curve of the efficacy and toxicity of different CCRT regimens for CC. Cluster analyses were used to group each category based on similar treatment regimens. Nineteen CSs were enrolled in this network meta-analysis, including 12 CCRT regimens (radiotherapy [RT], CCRT [cisplatin], CCRT [vinorelbine], CCRT [paclitaxel], CCRT [hydroxyurea], CCRT [cisplatin + FU], CCRT [cisplatin + gemcitabine], CCRT [cisplatin + docetaxel], CCRT [cisplatin + paclitaxel], CCRT [cisplatin + amifostine], CCRT [cisplatin + FU + hydroxyurea], and CCRT [cisplatin + vincristine + bleomycin]). The results of the network meta-analysis showed that regarding efficacy, the overall response rate of CCRT (cisplatin + docetaxel) was higher than RT, and the 5-year overall survival (OS) rate of CCRT (cisplatin + FU + hydroxyurea) was relatively higher than CCRT (hydroxyurea). As for toxicity, CCRT (cisplatin) had a lower incidence of leukopenia than CCRT (hydroxyurea), CCRT (cisplatin + FU) and CCRT (cisplatin + paclitaxel), and the incidences of diarrhea and vomiting in CCRT (cisplatin) were lower than those in CCRT (cisplatin + gemcitabine). Additionally, the cluster analysis showed that CCRT (cisplatin) had relatively lower incidences of both hematotoxicity and gastrointestinal toxicity, and CCRT (paclitaxel) had lower gastrointestinal toxicity than other regimens. Our study demonstrated that CCRT (cisplatin + docetaxel) might be the best choice of CCRT regimens in the treatment of CC, and the 5-year OS rate of CCRT (cisplatin + FU + hydroxyurea) might be the highest among these different regimens. CCRT (cisplatin) might have the lowest toxicity among all the CCRT regimens.

Dosimetric analysis of 3D-conformal radiotherapy and intensity modulated radiotherapy for treatment of advanced stage cervical cancer: A comparative study

Purpose: The purpose of this study is to analyze the dosimetric parameters of three dimensional conformal radiotherapy (3DCRT), intensity modulated radiotherapy (IMRT) with seven and nine fields (7F-IMRT, 9F-IMRT) in selected advanced stage cervical cancer cases. Methods: Fifteen cases of cervical cancer (IIB to IIIB) were selected for retrospective analysis. All the cases were previously treated with 3DCRT technique with prescribed dose of 50 Gy in 25 fractions. For this study, plans with seven fields IMRT and nine fields IMRT were generated for all patients following Radiation Therapy Oncology Group (RTOG) guidelines. The plans were compared on the basis of planning target volume (PTV) coverage (dose to 1%, 5%, 95% and 99% of target), maximum dose and mean dose to organs at risk (OARs) and also doses at different volumes of OARs. Apart from this, uniformity index (UI), homogeneity index (HI), conformity index (CI) and dose spillage index (R50%) were also calculated with respect to PTV coverage. Results: The average dose value of PTV coverage for all three techniques were comparable and all the DVH indices for 7field IMRT (UI (1.04±0.01), HI (0.07 ±0.02), CI (0.75±0.03) and R50% (4.47±0.36)) were better than 3DCRT and 9F-IMRT techniques. All OAR doses were significantly reduced in 7F- IMRT compared to 3DCRT and 9F- IMRT. The target volumes ranged from 769.2 ml to 1375.6 ml with average target volume of 1071.9 ml (SD: 205.38 ml). Conclusion: This study showed that significant dose reduction to OARs could be achieved with seven field IMRT plans by maintaining the PTV coverage compared to 3DCRT or 9F- IMRT for treating cervical cancer in advanced stages particularly from IIB to IIIB.

The Impact of Systemic Therapy Beyond First-line Treatment for Advanced Cervical Cancer

AimsDespite recent advances in the primary and secondary prevention of cervical cancer, a significant number of women present with or develop metastatic disease. There is currently no consensus on the standard of care for second-line systemic treatment of recurrent/metastatic cervical cancer. The purpose of this study was to evaluate the second-line systemic therapy used and the associated outcomes in a single cancer centre. Materials and methodsA retrospective review of patients with cervical cancer who received one or more lines of treatment for recurrent or metastatic cervical cancer at the Royal Marsden Hospital between 2004 and 2014 was carried out. The primary objective was to establish the types of second-line systemic treatment used. Secondary end points included objective response rate, progression-free survival and overall survival after second-line therapy. ResultsIn total, 75 patients were included in the study; 53 patients (70.7%) received second-line therapy for recurrent/metastatic disease. The most common second-line therapy was weekly paclitaxel (28.3%). Carboplatin-based chemotherapy (24.5%), targeted agent monotherapy within clinical trials (22.6%), docetaxel-based chemotherapy (13.2%), topotecan (9.4%) and gemcitabine (1.9%) were also used. The objective response rate to second-line therapy was 13.2%, which included three partial responses to carboplatin and paclitaxel, two partial responses to docetaxel-based chemotherapy, one partial response to weekly paclitaxel and one partial response to cediranib. Twenty-two patients (41.5%) achieved stable disease at 4 months. The median progression-free survival for women treated with second-line therapy was 3.2 months (95% confidence interval 2.1–4.3) and median overall survival was 9.3 months (95% confidence interval 6.4–12.5). Thirty-nine per cent of patients received third-line therapy. ConclusionSeventy per cent of patients treated with first-line systemic therapy for recurrent/metastatic cervical cancer subsequently received second-line treatment but response rates were poor. There remains no standard of care for second-line systemic therapy for advanced cervical cancer. Patients should be considered for clinical trials whenever feasible, including novel targeted agents and immunotherapy.

Use of Palliative Cisplatinum for Advanced Cervical Cancer in a Resource-Poor Setting: A Case Series From Kenya.

PurposeTo evaluate the effectiveness and feasibility of cisplatinum for palliative treatment of advanced cervical cancer in a resource-poor setting.MethodsAn observational case series is reported from a university teaching hospital in Kenya. All women presenting with advanced cervical cancer and planned for palliative cisplatinum therapy from 2010 to 2014 were included. Women were treated with cisplatinum 50 mg/m2 every 4 weeks in an outpatient setting. Data on tumor stage and symptoms control were prospectively collected in an electronic database. The main outcome measure was control of symptoms such as bleeding, discharge, and pain.ResultsOf the women who originally presented with bleeding, 62% reported improvement in this symptom, 31.3% reported the bleeding completely stopped, 58% had improvement of their vaginal discharge, and 20.5% reported complete resolution. Of the women who presented with pain, 54% reported improvement; 30.9% reported pain had completely resolved. After each treatment cycle, approximately 30% of patients did not return for their next treatment.ConclusionCisplatinum as palliative treatment of advanced cervical cancer is feasible in a resource-poor setting and leads to effective symptom control. However, unknown barriers may inhibit women from returning for regular treatment.

Weekly Cisplatin and Volumetric Modulated Arc Therapy With Simultaneous Integrated Boost for Radical Treatment of Advanced Cervical Cancer in Elderly Patients: Feasibility and Clinical Preliminary Results

Weekly Cisplatin and Volumetric Modulated Arc Therapy With Simultaneous Integrated Boost for Radical Treatment of Advanced Cervical Cancer in Elderly Patients: Feasibility and Clinical Preliminary Results