Cisplatin-based Concurrent Chemoradiotherapy Research Articles

Long-term outcomes of concomitant chemoradiotherapy incorporating high-dose-rate brachytherapy to treat locally advanced cervical cancer.

We reviewed the long-term clinical outcomes of patients treated with cisplatin-based concurrent chemoradiotherapy (CCRT) incorporating high-dose-rate (HDR) intracavitary brachytherapy (ICBT) in terms of toxicity, local control and survival rates. In addition, we identified prognostic factors for overall and disease-free survival. . Two hundred and nine patients with stage IB2-IVA cervical cancer underwent curative cisplatin-based CCRT plus HDR ICBT. Women with stage IB2-IIB disease were given 41.4 Gy of external radiotherapy followed by 35 Gy (in 7 fractions) of ICBT. Women with stage IIIA-IVA were given 50.4 Gy followed by 30 Gy (in 6 fractions) of ICBT. Patients with parametrial disease or pelvic lymphadenopathy were given parametrial boosts via external beam radiation at a dose of up to 65 Gy to thickened and 60 Gy to unthickened parametrial regions. One hundred and thirty (62%) patients experienced acute grade 3-4 hematological toxicities and 11 (5%) patients had late grade 3 gastrointestinal or genitourinary complications. Complete responses occurred in 168 (80%) women as determined by clinical and imaging studies. The median follow-up period was 52 months for surviving patients and the 5-year overall and disease-free survival rates were 74% and 67%, respectively. Multivariate analysis indicated that tumor size and paraaortic lymph node involvement were prognostically significant in terms of overall survival, and that tumor diameter was a significant prognostic factor and pelvic lymph node status a marginally significant prognostic factor for disease-free survival. Patients treated with our current HDR ICBT protocol have acceptably low late complication rates and local control and survival rates comparable to those reported in other studies. Tumor diameter was an important prognostic factor in terms of both overall and disease-free survival, emphasizing the need for modern ICBT methodologies.

Predictive value of excision repair cross-complementation group 1 protein in locoregionally advanced nasopharyngeal carcinomas receiving cisplatin-based concurrent chemoradiotherapy.

To investigate the ability of excision repair cross-complementation group 1 (ERCC1) protein to predict cisplatin-based concurrent chemoradiotherapy (CCRT) response in locoregionally advanced nasopharyngeal carcinoma (NPC). The clinical data of 205 patients with locoregionally advanced NPC, who received cisplatin-based CCRT, were analyzed retrospectively. Immunohistochemical analysis was used to assess the ERCC1 expression in nasopharyngeal tumor tissues. Receiver operating characteristic (ROC) curve analysis, univariate and multivariate Cox proportional hazards analyses were performed to evaluate the association between ERCC1 expression and failure-free survival (FFS), overall survival (OS), locoregional-FFS (L-FFS), and distant-FFS (D-FFS). Our results revealed that although the overall response rate in patients with high-ERCC1 expression (97.3%) and those with low-ERCC1 expression (100.0%) were not statistically different, but treatment-sensitive group displayed significantly lower ERCC1 expression in comparison to the treatment-resistant group (P = 0.001). The Kaplan-Meier plots revealed that the low-ERCC1 expression was significantly associated with better L-FFS, FFS, and OS of locally advanced NPC patients receiving cisplatin-based CCRT. Both univariate and multivariate analysis demonstrated that the ERCC1 expression, tumor node metastasis stage and performance status were independent predictors of OS and FFS. ERCC1 expression may be a useful predictive marker in patients with locoregionally advanced NPC, who are receiving cisplatin-based CCRT.

Retraction: Predictive value of excision repair cross-complementation group 1 protein in locoregionally advanced nasopharyngeal carcinomas receiving cisplatin-based concurrent chemoradiotherapy.

[This corrects the article DOI: 10.4103/0973-1482.165866].

The efficacy and toxicities of intensive induction chemotherapy followed by concurrent chemoradiotherapy in nasopharyngeal carcinoma patients with N3 disease

To assess the feasibility, efficacy and safety of 4 cycles of induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CRT) in nasopharyngeal carcinoma (NPC) patients with N3 disease. ICT consisting of paclitaxel (135 mg/m2) and nedaplatin (80 mg/m2) given every 3 weeks for 4 cycles followed by cisplatin-based CRT was planned. 22 patients completed 4 cycles of TP regimen ICT and the CRT according to the protocol. After 4 cycles of ICT, the ORR of the primary site was 100% (CR 22.7%, PR 77.3%), and that of the cervical lymph nodes was 95.5% (CR 27.3%, PR 68.2%). After the completion of CRT, the ORR of the primary site was 100% (CR 81.8%, PR 18.2%), and that of the cervical lymph nodes also reached 100% (CR 86.4%, PR 3.6%). The main hematological adverse events were grade 1 to 2 (G1/G2) neutropenia/anemia without febrile neutropenia. The most frequent toxicities during CRT were G1/G2 neutropenia, asthenia, oropharyngeal mucositis and skin injury. The median follow-up time was 46.5 (14 to 75) months. The 3-year PFS, DMFS, LRFS and OS were 81.8%, 81.8%, 100%, and 90.9%, respectively. The results suggest that intensive ICT followed by CRT in NPC patients with N3 disease is effective and well tolerated.

IER5 as a promising predictive marker promotes irradiation-induced apoptosis in cervical cancer tissues from patients undergoing chemoradiotherapy

PurposeTo define the role of immediate-early 5 (IER5) gene as a promising biomarker in predicting the radiosensitivity and prognosis of cervical cancer patients receiving cisplatin-based concurrent chemoradiotherapy (DDP-CCRT).ResultsOur investigations found that IER5 level was markedly elevated in cervical cancer patients after being treated with irradiation, which indicated IER5 was closely dose induced. By contrast, the correlation between IER5 and radiosensitivity cannot be confirmed by the present study. The up-regulation of IER5 expression effectively increased cell apoptosis after administration of irradiation (P < 0.05). Using an ANOVA model for repeated-measures, we found significant association between the IER5 level and tumor size (P < 0.05).Materials and MethodsForty-three cervical cancer patients stage IIb-IIIb received DDP-CCRT were registered. Biopsy tissues were obtained after administration of irradiation dose of 0 Gy, 2~6 Gy, 10 Gy, 20 Gy, 30 Gy, respectively. The IER5 protein and mRNA levels were measured by immunohistochemistry, western blot and quantitative polymerase chain reaction, respectively; besides, the apoptosis rate was assessed by transferase-mediated dUTP nick end labeling.ConclusionsMechanistically, we confirmed that IER5 induced by radiation dose enhanced apoptosis of cervical cancer, was inversely associated with tumor size. In conclusion, our studies indicate target IER5 is improved to be a potential radiosensitizer for developing effective therapeutic strategies against cervical cancer to radiotherapy and a predictive biomarker for radiosensitivity.

The Efficacy of Palonosetron Plus Dexamethasone in Preventing Chemoradiotherapy-induced Nausea and Emesis in Patients Receiving Daily Low-dose Cisplatin-based Concurrent Chemoradiotherapy for Uterine Cervical Cancer

The prevention of chemotherapy-induced and radiotherapy-induced emesis is recommended by several guidelines; however, there are no evidence-based recommendations for the use of antiemetics in concurrent chemoradiotherapy (CCRT). The aim of the present study was to evaluate the efficacy and safety of antiemetic therapy comprising palonosetron and dexamethasone during CCRT. This is a nonrandomized, prospective, single-center, open phase II study.Twenty-six consecutive patients with cervical carcinoma were treated with daily low-dose cisplatin (8 mg/m/d)-based CCRT (2 Gy/d, 25 fractions, 5 times a week). All patients received 0.75 mg of palonosetron on day 1 of each week and 4 mg of oral dexamethasone daily. The primary endpoint was the percentage of patients achieving a complete response, which was defined as no emetic episodes and no antiemetic rescue medication during treatment. Planned daily low-dose cisplatin-based CCRT was successful without delay or interruption in 46% (12/26) of the patients. The mean dose of total cisplatin was 184 (range, 136 to 200) mg/m.No patient vomited during the treatment period. The complete response rate during CCRT was 100%. A total of 81% patients were completely free from nausea. All patients tolerated the combination of palonosetron and dexamethasone and completed the scheduled regimen. Five patients exhibited grade 1 Cushingoid features that resolved after treatment. Antiemetic therapy comprising palonosetron and dexamethasone provided complete protection from nausea and vomiting in patients with cervical cancer receiving daily low-dose cisplatin-based CCRT.

Clinical Impact of Escalating Relative High-dose-rate Intracavitary Brachytherapy Dose in Stage IIB Cervical Cancer.

To investigate whether high-dose-rate (HDR) intracavitary brachytherapy (IBT) dose ratios can predict treatment outcomes in patients with stage IIB cervical cancer. Ninety-three patients treated with weekly cisplatin-based concurrent chemoradiotherapy and HDR IBT were analyzed. Potential prognostic factors and treatment outcomes were compared between low-HDR-IBT-ratio (≤0.43) and high-HDR-IBT-ratio (>0.43) groups, and univariate and multivariate analyses were performed. Five-year disease-specific survival (DSS) and progression-free survival (PFS) rates were significantly shorter in the low-compared to the high-HDR-IBT-ratio group. A high HDR IBT ratio was confirmed as an independent prognostic factor for DSS and PFS. A high HDR IBT dose ratio improves DSS and PFS in patients with stage IIB cervical cancer. Therefore, active administration of HDR IBT beyond previously accepted levels may be necessary for the treatment of locally advanced cervical cancer.

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

A pilot study of concurrent chemoradiotherapy with gemcitabine and cisplatin in patients with locally advanced biliary tract cancer.

Combination chemotherapy with gemcitabine and cisplatin is a standard treatment for patients with advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of gemcitabine- and cisplatin-based concurrent chemoradiotherapy in patients with unresectable biliary tract cancer. Patients with pathologically proven, unresectable, non-metastatic biliary tract cancer were enrolled. Gemcitabine was administered intravenously at a dose of 1000mg/m(2) on days 1, 8, and 15. Cisplatin was administered intravenously at a dose of 70mg/m(2) on day 1. All the patients underwent concurrent radiotherapy with 45Gy in 1.8-Gy daily fractions. After treatment completion, tumor response was evaluated by using computed tomography. Eighteen patients were enrolled between June 2007 and October 2011. Their median age was 61years (range, 38-72years). Eight patients (44.5%) were diagnosed with gallbladder cancer, six (33.3%) with Klatskin's tumor, and four (22.2%) with distal common bile duct cancer. After treatment completion, partial response was achieved in five patients (27.8%) and stable disease in 13 patients (72.2%). The overall response rate was 27.8%, and the disease stabilization rate was 100%. No grade 4 adverse events or treatment-related deaths occurred. The most common grade 3 adverse events were thrombocytopenia (33.3%) and anemia (11.1%). The median progression-free and overall survival times were 6.8months (range, 4.5-19.8months) and 9.6months (5.4-30.4months), respectively. This study shows that gemcitabine- and cisplatin-based concurrent chemoradiotherapy is feasible and tolerable in patients with unresectable and non-metastatic biliary tract cancer.

ORCA-2: A phase I study of olaparib in addition to cisplatin-based concurrent chemoradiotherapy for patients with high risk locally advanced squamous cell carcinoma of the head and neck.

TPS6108Background: Standard care for locally advanced squamous cell carcinoma of the head and neck (HNSCC) is cisplatin-based chemoradiotherapy (C-CRT). Use of intensity modulated radiotherapy (IMR...

Association of DNA repair gene polymorphisms with response to cisplatin-based concurrent chemoradiotherapy in patients with cervical carcinoma.

The aim of this study was to investigate polymorphisms in DNA repair genes as potential predictive factors among Chinese cervical cancer patients. A total of 72 patients with cervical carcinoma, who received cisplatin-based chemoradiotherapy and whose responses were evaluated by Response Evaluation Criteria in Solid Tumors, were included. The association between response to chemoradiotherapy and the genotypes for 29 single-nucleotide polymorphisms (SNPs) in 25 DNA repair genes were analyzed. A minor allele of SNP rs9350 in the exonuclease 1 gene was associated with a better response rate, regardless of age and tumor stage (odds ratio, 8.316; p=0.002). SNP rs9350 in the exonuclease 1 gene is involved in inter-individual differences in the response to cisplatin-based chemoradiotherapy, in patients with cervical carcinoma.

Concurrent cisplatin-based chemoradiotherapy versus exclusive radiotherapy in high-risk cervical cancer: a meta-analysis.

ObjectiveTo evaluate the efficacy and safety of cisplatin-based concurrent chemoradiotherapy (DDP-CCRT) in patients with high-risk cervical carcinoma (CC) compared with exclusive radiotherapy (RT).Materials and methodsDatabases were searched for randomized controlled trials (RCTs) and cohort studies comparing DDP-CCRT with RT alone. Risk of bias assessment for RCTs was performed using the Cochrane Collaboration’s tool, and the Newcastle–Ottawa quality scale was used to perform quality assessment for cohort studies. Meta-analysis was conducted using Review Manager 5 and Stata 12.0 software.ResultsFinally, eight RCTs and three cohort studies containing 2,130 subjects were included. Analysis on total failures revealed a statistically significant difference in favor of DDP-CCRT (risk ratio =0.77, 95% confidence intervals [CIs]: 0.67–0.89). No significant heterogeneity was detected for pooled analysis concerning overall survival; the result of which demonstrated the superiority of DDP-CCRT over RT alone (hazard ratio =0.68, 95% CI: 0.57–0.80), and stable and established accumulative effects were observed in cumulative meta-analysis. Similar results were observed for progression-free survival (hazard ratio =0.63, 95% CI: 0.50–0.76). In terms of treatment-related Grade 3 and 4 adverse events, our pooled analysis with a fixed-effects model showed significantly enhanced toxicity in the DDP-CCRT group compared with that in the RT group (odds ratio =3.13, 95% CI: 2.37–4.13).ConclusionSolid and stable beneficial effects are associated with DDP-CCRT, and its superiority over comparative RT in patients with high-risk CC is confirmed. DDP-CCRT should be considered one of the frontline treatment options for high-risk CC patients without contraindications. However, enhanced toxicity associated with DDP-CCRT should never be ignored.

Assessment of voice, speech, and related quality of life in advanced head and neck cancer patients 10-years+ after chemoradiotherapy

Assessment of long-term objective and subjective voice, speech, articulation, and quality of life in patients with head and neck cancer (HNC) treated with concurrent chemoradiotherapy (CRT) for advanced, stage IV disease. Twenty-two disease-free survivors, treated with cisplatin-based CRT for inoperable HNC (1999-2004), were evaluated at 10-years post-treatment. A standard Dutch text was recorded. Perceptual analysis of voice, speech, and articulation was conducted by two expert listeners (SLPs). Also an experimental expert system based on automatic speech recognition was used. Patients' perception of voice and speech and related quality of life was assessed with the Voice Handicap Index (VHI) and Speech Handicap Index (SHI) questionnaires. At a median follow-up of 11-years, perceptual evaluation showed abnormal scores in up to 64% of cases, depending on the outcome parameter analyzed. Automatic assessment of voice and speech parameters correlated moderate to strong with perceptual outcome scores. Patient-reported problems with voice (VHI>15) and speech (SHI>6) in daily life were present in 68% and 77% of patients, respectively. Patients treated with IMRT showed significantly less impairment compared to those treated with conventional radiotherapy. More than 10-years after organ-preservation treatment, voice and speech problems are common in this patient cohort, as assessed with perceptual evaluation, automatic speech recognition, and with validated structured questionnaires. There were fewer complaints in patients treated with IMRT than with conventional radiotherapy.

Prognostic Value of Plasma Epstein-Barr Virus DNA for Local and Regionally Advanced Nasopharyngeal Carcinoma Treated With Cisplatin-Based Concurrent Chemoradiotherapy in Intensity-Modulated Radiotherapy Era.

This study aimed to evaluate the prognostic value of plasma Epstein–Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level <4000 copies/mL, patients with an EBV DNA ≥4000 copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68–84]) versus (93%, 95% CI [90–96], P < 0.001), DMFS (83%, 95% CI [76–89]) versus (97%, 95% CI [94–99], P < 0.001), and OS (85%, 95% CI [78–92]) versus (98%, 95% CI [95–100], P < 0.001). Multivariate analysis showed that pretreatment EBV DNA levels (HR = 3.324, 95% CI, 1.80–6.138, P < 0.001) and clinical stage (HR = 1.878, 95% CI, 1.036–3.404, P = 0.038) were the only independent factor associated with PFS, pretreatment EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647–14.956, P < 0.001), and pretreatment EBV DNA levels (HR = 3.753, 95% CI, 1.701–8.284, P < 0.001) and clinical stage (HR = 2.577, 95% CI, 1.252–5.050, P = 0.010) were significantly associated with OS. In subgroup analysis, higher plasma EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized clinical trials are needed to further evaluate whether plasma EBV DNA levels could be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients.

Sequential Chemoradiotherapy による stage Ⅳ 進行頭頸部癌33症例の治療成績

A total of 33 patients with advanced head and neck cancer (AHNC) treated with sequential chemoradiotherapy (SCRT) were retrospectively evaluated at Gunma University Hospital between 2009 and 2011. The regimen of SCRT was docetaxel, cisplatin, and fluorouracil (TPF)-based induction chemotherapy (ICT), accompanied by docetaxel and cisplatin-based concurrent chemoradiotherapy (CCRT), and oral administration of TS-1 after that. The response rate was 61%, the 3-year overall survival rate was 42%, the non-tumor-bearing survival rate was 27%, and the tumor-bearing survival rate was 15%. Fourteen of 33 patients were tumor-free, and their 3-year overall survival rate was surprisingly 86%. On the other hand, 3-year overall survival rate in the remaining 19 patients was significantly low. To select good response cases for ICT was important. In such cases, TPF should be applied repeatedly, which achieved a 61% response rate even in AHNC. A long-term TS-1 oral medication suppressed cancer regrowth and contributed to long-term survival.

Prognostic Value of Neutrophil-Related Factors in Locally Advanced Cervical Squamous Cell Carcinoma Patients Treated with Cisplatin-Based Concurrent Chemoradiotherapy.

The aim of this study was to explore the relationship between neutrophil-related factors, including neutrophil-lymphocyte ratio (NLR) and the responses of neutrophil to granulocyte colony-stimulating factors (RNG), and the prognosis of patients with locally advanced cervical squamous cell carcinoma (LACSCC) undergoing cisplatin-based concurrent chemoradiotherapy (CCCRT). A total of sixty LACSCC patients were enrolled in this study. We analyzed the association of NLR or RNG with clinicopathologic characteristics of these patients. The prognostic factors were evaluated by univariate and multivariate survival analysis. The optimal cut-off value of the NLR was determined to be 2.0 for the overall survival (OS). A higher level of the NLR was associated with younger age (P = 0.017) and higher baseline platelet count (P = 0.040). NLR was identified to be the only independent prognostic factor for OS by multivariate analysis (P = 0.037). The median RNG was 3.01, with a range of 1.19–16.84. RNG level was significantly associated with lymph node metastasis of these patients (P = 0.023). And higher RNG was identified as being a closely independent poor prognostic factor for OS (P = 0.055). This study showed that NLR and RNG may be used as potential biomarkers for survival prediction in patients with LACSCC receiving CCCRT.

Cetuximab and Cisplatin Show Different Combination Effect in Nasopharyngeal Carcinoma Cells Lines via Inactivation of EGFR/AKT Signaling Pathway.

Nasopharyngeal carcinoma (NPC) is a common malignant cancer in South China. Cisplatin is a classical chemotherapeutic employed for NPC treatment. Despite the use of cisplatin-based concurrent chemoradiotherapy, distant failure still confuses clinicians and the outcome of metastatic NPC remains disappointing. Hence, a potent systemic therapy is needed for this cancer. Epidermal growth factor receptor (EGFR) represents a promising new therapeutic target in cancer. We predicted that combining the conventional cytotoxic drug cisplatin with the novel molecular-targeted agent cetuximab demonstrates a strong antitumor effect on NPC cells. In this study, we selected HNE1 and CNE2 cells, which have been proved to possess different EGFR expression levels, to validate our conjecture. The two-drug regimen showed a significant synergistic effect in HNE1 cells but an additive effect in CNE2 cells. Our results showed that cisplatin-induced apoptosis was significantly enhanced by cetuximab in the high EGFR-expressing HNE1 cells but not in CNE2 cells. Further molecular mechanism study indicated that the EGFR/AKT pathway may play an important role in cell apoptosis via the mitochondrial-mediated intrinsic pathway and lead to the different antitumor effects of this two-drug regimen between HNE1 and CNE2 cells. Thus, the regimen may be applied in personalized NPC treatments.

Prospective randomized study comparing concomitant chemoradiotherapy using weekly cisplatin & paclitaxel versus weekly cisplatin in locally advanced carcinoma cervix.

To evaluate the benefit with the addition of paclitaxel to cisplatin-based concurrent chemoradiotherapy (C-CRT) for the treatment of locally advanced carcinoma of the uterine cervix in terms of local control, disease free survival (DFS) and overall survival (OS). From 1/7/2011 to 31/5/2012, 81 women (median age of 50 years) with newly diagnosed, histopathologically proven carcinoma cervix with FIGO stages IIA to IIIB were randomized to two arms-cisplatin 40 mg/m(2)/week for 5 weeks was given in single agent cisplatin (control arm), while cisplatin 30 mg/m(2)/week and paclitaxel 50 mg/m(2)/week for 5 weeks were given in cisplatin and paclitaxel (study arm). External beam radiotherapy (EBRT) was delivered to a total dose of 50 Gray (Gy) in 25 fractions (#) followed by intracavitary (I/C) brachytherapy or supplement EBRT at 20 Gy/10# with 2 cycles of respective chemotherapy. This prospective trial was registered with clinicaltrials.gov (NCT01593306). Patients (n=81) had a maximum follow up of 36 months with a median follow up of 29 months. At first follow up study arm showed complete response in 84% vs. 75.6% in control arm (P=0.4095). An increase in toxicities was observed in the study arm in comparison to the control arm in terms of haematological grade II (35% vs. 12.2%), gastrointestinal (GI) grade III (20% vs. 7.4%) and GI grade IV (12.5% vs. 2.4%) toxicities. At median follow-up, the study arm demonstrated enhanced outcomes over the control arm in terms of DFS (79.5% vs. 64.3%; P=0.07) and OS (87.2% vs. 78.6%; P=0.27). Despite the expected increase in manageable toxicities, these early results reveal promise with the inclusion of paclitaxel into the standard cisplatin based chemoradiation regime. Larger multi-institutional studies are justified to confirm a potential for the enhancement of response rates and survival.

Evaluation of Outcomes in Patients With Carcinoma of the Cervix Treated With Concurrent Radiation and Cisplatin Versus Cisplatin/5-FU Compared With Radiation Alone

The objective of this study was to compare outcomes for patients with cervical cancer treated with radiation concurrently with cisplatin, cisplatin/5-fluorouracil (5-FU), or without chemotherapy. We reviewed the records of eligible patients with locoregionally confined, stage IB1 through IVA, intact cervical cancer who were treated at Northwestern Memorial Hospital. All patients underwent definitive radiotherapy with combined external beam radiation-the majority with extended-field (62%)-and received low-dose rate brachytherapy. A total of 236 patients were included: 99 had no concurrent chemotherapy, 95 were treated with concurrent cisplatin, and 42 were treated with cisplatin/5-FU. For all patients treated with or without chemotherapy, overall survival at 5 and 10 years was 64% and 59%, respectively. Patients treated with chemotherapy had a superior recurrence-free survival rate of 69% at 5 years versus 49% in patients who did not receive chemotherapy (P=0.09). Twenty-six percent of patients treated with cisplatin alone, 31% of patients treated with cisplatin/5-FU, and 45% of patients who did not receive chemotherapy experienced a disease recurrence. Adenosquamous histology conferred a higher rate of recurrence as compared with adenocarcinoma and squamous cell histologies (54% vs. 34%, respectively; P=0.05). Cisplatin-based concurrent chemoradiotherapy showed a trend toward improved recurrence-free survival survival in the definitive treatment of nonmetastatic cervical cancer. The addition of 5-FU to cisplatin did not appear to significantly impact survival or recurrence-free survival. Adenosquamous histology was associated with a higher risk of recurrence as compared with other histologic subtypes.

Relationship between excision repair cross-complementation group 1 methylation and sensitivity to cisplatin-based concurrent chemoradiotherapy in cervical squamous cell carcinoma

Objective To investigate the correlation of the excision repair cross-complementation group 1(ERCC1) gene methylation status with sensitivity to cisplatin-based concurrent chemoradiotherapy and clinical pathological characteristics in patients with cervical squamous cell carcinoma (CSCC). Methods Methylation specific polymerase chain reaction was used to determine the ERCC1 gene methylation status in cervical tissue from 20 healthy people and 60 patients with CSCC. All patients with CSCC were treated with cisplatin-based concurrent chemoradiotherapy. The treatment outcomes were evaluated using the Response Evaluation Criteria in Solid Tumors. Based on the treatment outcomes, patients with a complete response were assigned to chemoradiotherapy-sensitive group, and patients with a partial response, stable disease, or progressive disease were assigned to chemoradiotherapy-resistant group. Comparison of the ERCC1 gene methylation status between the two groups was made by χ2 test, and multivariate logistic regression analysis was used to analyze the relationship of the ERCC1 gene methylation status with various clinical pathological characteristics and sensitivity to chemoradiotherapy. Results The ERCC1 gene methylation rate was significantly higher in cervical tissue with CSCC than in normal cervical tissue (60% vs. 0%, P=0.000). The multivariate analysis showed that ERCC1 gene methylation was an independent influencing factor for sensitivity to cisplatin-based concurrent chemoradiotherapy in CSCC (P=0.022); ERCC1 gene methylation was significantly correlated with histological grade of CSCC (P=0.030); there was no significant relationship of ERCC1 gene methylation with clinical pathological characteristics including age, tumor size, lymph node metastasis, FIGO stage, and pretreatment hemoglobin and platelet count (P=0.729, 0.707, 0.340, 0.747, 0.073, 1.000). Conclusions The ERCC1 gene promoter methylation status may be involved in the development and progression of CSCC. It may also influence the sensitivity of patients with CSCC to cisplatin-based concurrent chemoradiotherapy by playing a role in cell differentiation. Key words: Excision repair cross-complementation group 1; Radiosensitivity; Cervical neoplasms/radiotherapy; Cervical neoplasms/chemotherapy