Impact of the Co-expression of EGFR and c-erb-B2 on Disease Free Survival of Patients with Advanced Cervical Cancer Treated with Chemo-radiotherapy

IntroductionSince the addition of chemotherapy to radiotherapy, the survival rates of locally advanced cervical cancer (LACC) have improved but are still disappointing. Therefore, the idea of surgery after chemoradiation in case of LACC or bulky disease was adopted. One of the concerns regarding surgery following chemoradiotherapy is surgery-related morbidity.AimThe objectives of this study were to investigate the feasibility of surgery after advanced radiotherapy techniques such as intensity-modulated arc therapy (IMAT) and to describe the morbidity.MethodsThis was a prospective study of primary inoperable LACC patients primary treated with IMAT, in most cases combined with weekly cisplatin. Then the resectability was reevaluated. If resectable patients were treated with Wertheim type 2 surgery ± pelvic lymphadenectomy (on positron emission tomography–computed tomography indication). If tumor is not resectable, patients were treated with brachytherapy.ResultsSince 2006, 41 consecutive patients were included. After neoadjuvant IMAT, 34 were considered resectable and underwent surgery, whereas 7 proceeded with brachytherapy. The operative mortality rate was nil. There were no major perioperative complications. No ureter, bladder, or bowel injuries occurred. No postoperative urinary/digestive fistulae or stenoses were noted. Eleven patients had postoperatively urinary retention problems. At the time of discharge, 5 patients still needed self-catheterization. All problems resolved within 3 months. In 4 cases, we saw significant lymphoceles. In all patients intended to treat, overall survival and disease-free survival at 3 years were 63% and 74%. In the Wertheim group, overall survival and disease-free survival at 3 years were 81% and 91%.ConclusionsCompleting surgery after chemoradiation therapy (with IMAT) for LACC or bulky disease is feasible, and complication rates are comparable with those of primary surgery for cervical cancer.

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EP237 Survival outcome and disease free survival of locally advanced cervical cancer with CT-detected para-aortic lymph nodes

10.1136/ijgc-2019-esgo.299 ◽

2019 ◽

Author(s):

JK Abrenica ◽

J Bagadiong

Keyword(s):

Cervical Cancer ◽

Lymph Nodes ◽

Locally Advanced ◽

Disease Free Survival ◽

Survival Outcome ◽

Advanced Cervical Cancer ◽

Free Survival ◽

Locally Advanced Cervical Cancer ◽

Disease Free

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Correlation between c-erb-B2 overexpression with disease-free survival and rate of pelvic relapse in patients with advanced cervical cancer treated with chemo-radiotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.16004 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 16004-16004

Author(s):

J. Pérez-Regadera ◽

A. Sánchez-Muñoz ◽

J. De-la-Cruz ◽

C. Ballestín ◽

D. Lora ◽

...

Keyword(s):

Cervical Cancer ◽

Disease Free Survival ◽

Concurrent Chemotherapy ◽

Immunohistochemical Method ◽

Advanced Cervical Cancer ◽

Pelvic Radiotherapy ◽

Free Survival ◽

The Impact ◽

Disease Free ◽

Pelvic Relapse

16004 Aims: To determine the impact of the c-erb-B2 overexpression receptor on pelvic relapse and on disease-free survival (DFS) in patients with advanced cervical cancer receiving concurrent chemo-radiotherapy. Methods: One hundred thirty six patients with advanced cervical cancer (stage: 12 IB2-IIA, 34 IIB, 71 IIIB, 19 IVA); histology: 86 epidermoid and 14 adenocarcinoma) were analyzed to detect c-erbB-2 level using an immunohistochemical method (Herceptest Dako). Cases c-erbB-2 (+3) were considered positive. All patients received pelvic radiotherapy, brachitherapy and concurrent chemotherapy with two schedules: 48 patients with tegafur (800 mg/day via oral) and 88 with tegafur (same doses) plus five cycles of weekly cisplatin 40 mg/m2/week iv. Results: Of the 136 biopsies, 32 (23.5%) were c- erbB-2 positive. The disease free survival to 3 and 5 years of the patients were 61% and 58% for c-erb-B2 negative and 36% and 36% for c-erb- B2 positive (p=0.02), respectively.We divided our patients in four groups: c-erb-B2 positive treated with cisplatin; c-erb-B2 positive without cisplatin, c-erb-b2 negative treated with cisplatin and c-erb-b2 negative without cisplatin. The group of patients with c-erb-B2 overexpression that did not received platinum treatment had a higher rate of pelvis relapse (p<0.0001) and with a decreased DFS (p=0.0014). Conclusions: c-erbB-2 overexpression may imply a poor prognosis for patients with advanced cervix cancer, especially if they did not receive concurrent radiochemotherapy with cisplatin. No significant financial relationships to disclose.

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Radiation with cisplatin or carboplatin for locally advanced cervix cancer: The experience of a tertiary cancer center.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15541 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15541-e15541

Author(s):

George Au-Yeung ◽

Linda R. Mileshkin ◽

David Bernshaw ◽

Srinivas Kondalsamy-Chennakesavan ◽

Danny Rischin ◽

...

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Locally Advanced ◽

Disease Free Survival ◽

Concurrent Chemotherapy ◽

Advanced Cervical Cancer ◽

Free Survival ◽

Locally Advanced Cervical Cancer ◽

Distant Failure ◽

Disease Free

e15541 Background: Definitive treatment with concurrent cisplatin and radiation is the standard of care for locally advanced cervical cancer. The optimal management of patients with a contraindication to cisplatin has not been established. We conducted a retrospective audit of the impact of concurrent chemoradiation in a cohort of patients (pts) with locally advanced cervical cancer. Methods: All pts with locally advanced cervical cancer treated with definitive radiation were entered into a prospective database. Information regarding their demographics, stage, histology, recurrence and survival were recorded. Pharmacy records were reviewed to determine concurrent chemotherapy use. The primary endpoint was overall survival, and secondary endpoints were disease free survival and rates of primary, nodal or distant failure. Univariate and multivariate analyses were performed, incorporating known prognostic factors of age, FIGO stage, uterine body involvement, tumour volume on MRI and nodal involvement. Results: 442 pts were treated from Jan 1996 to Feb 2011. Median age was 59 (range 22-94); 89% had squamous histology and 64% node-negative disease. 269 pts received cisplatin, 59 received carboplatin because of a contraindication to cisplatin and 114 received no concurrent chemotherapy (most prior to 1999). Overall survival adjusted for other prognostic factors was significantly improved with use of concurrent cisplatin compared to radiation alone (HR 0.53, p=0.001), as was disease free survival and the rate of distant failure. Use of concurrent carboplatin was not associated with any significant benefit compared to radiation alone in terms of overall survival or disease free survival on univariate or multivariate analyses. Conclusions: The results of this audit are consistent with the known significant survival benefit with concurrent cisplatin chemoradiation. However, there did not appear to be any significant benefit associated with concurrent carboplatin although there are potential confounding factors in this small cohort. The available evidence in the literature favors the use of non-platinum chemotherapy rather than carboplatin in pts with contraindications to cisplatin.

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Comparison of outcomes and side effects for neoadjuvant chemotherapy with weekly cisplatin and paclitaxel followed by chemoradiation vs. chemoradiation alone in stage IIB–IVA cervical cancer: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05986-z ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Jing Li ◽

Hua Liu ◽

Ya Li ◽

Jian Li ◽

Lifei Shen ◽

...

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Neoadjuvant Chemotherapy ◽

Locally Advanced ◽

Disease Free Survival ◽

Phase Iii ◽

Advanced Cervical Cancer ◽

Free Survival ◽

Locally Advanced Cervical Cancer ◽

Disease Free

Abstract Background Currently, the standard treatment for locally advanced cervical cancer is concurrent chemoradiation (CCRT). The effect of neoadjuvant chemotherapy in advanced cervical cancer is controversial. Studies have shown that the addition of a weekly regimen of neoadjuvant chemotherapy (NACT) followed by CCRT may be superior to a thrice-weekly regimen of NACT and CCRT. Among patients who had not received prior cisplatin, a cisplatin and paclitaxel (TP) regimen resulted in longer overall survival than other regimens. This study aims to investigate the feasibility, safety, and efficacy of NACT with weekly TP followed by CCRT. Methods This is a prospective, randomized, open-labeled, multicentered phase III study. Based on a 65% of 2-year disease-free survival (DFS) rate in the CCRT group and 80% of that in NACT followed by CCRT group, and on prerequisite conditions including an 8% loss to follow-up, a two-sided 5% of type I error probability, and an 80% of power, a total of 300 cases were required for enrollment. Patients with IIB–IVA cervical cancer will be randomly allocated in a 1:1 ratio to one of two intervention arms. In the study arm, patients will receive dose-dense cisplatin (40 mg/m2) and paclitaxel (60 mg/m2) weekly for 4 cycles followed by CCRT (45 Gy in 5 weeks concurrent with cisplatin 40 mg/m2 weekly) plus image-guided adaptive brachytherapy (IGBRT). In the control arm, patients will undergo CCRT treatment. The primary endpoint of the study is 2-year disease-free survival (DFS); the secondary endpoints are 5-year overall survival (OS) and disease-free survival (DFS), the response rate 3 months after treatment completion, grade III/IV adverse effects, and quality of life, and potential biomarkers for predicting treatment response will also be studied. Discussion The data gathered from the study will be used to determine whether NACT with weekly TP followed by CCRT may become an optimized treatment for locally advanced cervical cancer. Trial registration Chinese Clinical Trial Registry ChiCTR1900025327. Registered on 24 August 2019. medresman.org.cn ChiCTR1900025326

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Adjuvant carboplatin and paclitaxel after concurrent cisplatin and radiotherapy in patients with locally advanced cervical cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2018-000022 ◽

2019 ◽

Vol 29 (1) ◽

pp. 42-47 ◽

Cited By ~ 6

Author(s):

Guler Yavas ◽

Cagdas Yavas ◽

Erdem Sen ◽

Irem Oner ◽

Cetin Celik ◽

...

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Locally Advanced ◽

Disease Free Survival ◽

Advanced Cervical Cancer ◽

Free Survival ◽

Locally Advanced Cervical Cancer ◽

Grade 3 ◽

Disease Free

IntroductionStandard treatment for locally advanced cervical cancer (LACC) includes concomitant chemoradiotherapy (CRT) that typically controls localized disease. However, most patients develop distant metastasis, ultimately leading to death.ObjectiveTo determine the role of adjuvant carboplatin and paclitaxel for clinical outcomes in patients with LACC.MethodsBetween 2010 and 2017, 109 patients with LACC were retrospectively evaluated. All patients received cisplatin (40 mg/m2) with concurrent external-beam radiotherapy (up to 50.4 Gy), followed by intra-cavitary brachytherapy. Forty-six of 109 patients received a median of six cycles (range 3–6 cycles) of adjuvant chemotherapy consisting of paclitaxel (175 mg/m2) and carboplatin (CRT + chemotherapy group; area under the curve 5). The remaining 63 patients did not receive adjuvant chemotherapy (CRT group).ResultsDisease-free survival and overall survival after a median follow-up of 24.5 months (range 2.6–94.75 months) were 93.5% and 95.7% and 69.8% and 82.5 % for the CRT + chemotherapy and CRT groups, respectively (p = 0.001, p = 0.012, respectively). No acute grade 3/4 gastrointestinal or genitourinary toxicities were seen during CRT. During adjuvant chemotherapy, the most troublesome side effects were hematologic and neurologic toxicities; however, most were manageable. No chronic grade 3/4 genitourinary toxicities were seen.DiscussionAdjuvant chemotherapy in patients with LACC significantly improved both disease-free survival and overall survival without increasing unmanageable toxicity. Future larger prospective trials are warranted to verify these findings.

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Surgical versus clinical staging prior to primary chemoradiation in patients with cervical cancer FIGO stages IIB–IVA: oncologic results of a prospective randomized international multicenter (Uterus-11) intergroup study

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-001973 ◽

2020 ◽

Vol 30 (12) ◽

pp. 1855-1861 ◽

Cited By ~ 2

Author(s):

Simone Marnitz ◽

Audrey Tieko Tsunoda ◽

Peter Martus ◽

Marcelo Vieira ◽

Renato Jose Affonso Junior ◽

...

Keyword(s):

Cervical Cancer ◽

Locally Advanced ◽

Disease Free Survival ◽

Surgical Staging ◽

Clinical Staging ◽

Advanced Cervical Cancer ◽

Cancer Specific Survival ◽

Free Survival ◽

Locally Advanced Cervical Cancer ◽

Disease Free

ObjectiveRevised staging of patients with locally advanced cervical cancer is based on clinical examination, imaging, and potential surgical findings. A known limitation of imaging techniques is an appreciable rate of understaging. In contrast, surgical staging may provide more accurate information on lymph node involvement. The aim of this prospective study was to evaluate the impact of pre-treatment surgical staging, including removal of bulky lymph nodes, on disease-free survival in patients with locally advanced cervical cancer.MethodsUterus-11 was a prospective international multicenter study including patients with locally advanced cervical cancer who were randomized 1:1 to surgical staging (experimental arm) or clinical staging (control arm) followed by primary platinum-based chemoradiation. Patients with histologically proven squamous cell carcinoma, adenocarcinoma, or adenosquamous cancer International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIB–IVA underwent gynecologic examination and pre-treatment imaging including abdominal computed tomography (CT) and/or abdominal magnetic resonance imaging (MRI). Patients had chest imaging (any of the following: X-ray, CT, or PET-CT). The primary endpoint was disease-free survival and the secondary endpoint was overall survival. An ad hoc analysis was performed after trial completion for cancer-specific survival. Randomization was conducted from February 2009 to August 2013.ResultsA total of 255 patients (surgical arm, n=130; clinical arm, n=125) with locally advanced cervical cancer were randomized. Of these, 240 patients were eligible for analysis. The two groups were comparable with respect to patient characteristics. The surgical approach was transperitoneal laparoscopy in most patients (96.6%). Laparoscopic staging led to upstaging in 39 of 120 (33%) patients. After a median follow-up of 90 months (range 1–123) in both arms, there was no difference in disease-free survival between the groups (p=0.084). For patients with FIGO stage IIB, surgical staging is superior to clinical staging with respect to disease-free survival (HR 0.51, 95% CI 0.30 to 0.86, p=0.011). In the post-hoc analysis, surgical staging was associated with better cancer-specific survival (HR 0.61, 95% CI 0.40 to 0.93, p=0.020).ConclusionOur study did not show a difference in disease-free survival between surgical and clinical staging in patients with locally advanced cervical cancer. There was a significant benefit in disease-free survival for patients with FIGO stage IIB and, in a post-hoc analysis, a cancer-specific survival benefit in favor of laparoscopic staging. The high risk of distant metastases in both arms emphasizes the need for further evaluation.

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Fused in Sarcoma (FUS) Expression May Predict Survival Outcomes of Patients With Advanced Squamous Cell Cervical Carcinoma

10.21203/rs.3.rs-841588/v1 ◽

2021 ◽

Author(s):

Ana Maria Dias Fachini ◽

Luís Otávio Sarian ◽

Maria Cecília Ramiro Talarico ◽

Rafaella Almeida Lima Nunes ◽

Larissa Bastos Eloy Costa ◽

...

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Disease Free Survival ◽

Advanced Cervical Cancer ◽

Free Survival ◽

Fused In Sarcoma ◽

Disease Free ◽

Fus Protein ◽

Related Survival

Abstract Because of its role in preserving DNA/RNA stability, there is an increasing number of studies addressing the relationship between Fused in Sarcoma (FUS) expression and cancer. However, the disparity in FUS/FUS oncogenic vs. tumor-suppressive roles may be attributed to the complex molecular pathways associated with FUS regulation in different cancer types, and its role in cervical carcinogenesis remains largely unexplored. Methods: We determined FUS protein expression in specimens of 61 patients with advanced cervical cancer. Long-term (> 10 years) clinical follow-up data for these patients were available, and we determined disease-free, cancer-related and overall survival as related to FUS expression. Results: There were no significant associations between FUS expression and patients’ age, tumor grade, and acute/late toxicity events related to treatment (either radiation alone or chemoradiation). However, multivariate Cox regression analysis for disease-free survival (recurrence), overall survival (death) and cancer-related survival showed that patients with high average FUS expression fared significantly better than their counterparts with low average FUS expression, both in terms of disease-free survival (HR = 0.31; 95%CI 0.12 to 0.77; p = 0.01) and cancer-related survival (HR = 0.41; 95%CI 0.17 to 0.98; p = 0.04). Conclusions: Our study shows that high FUS protein expression in advanced cervical cancer specimens is a potent harbinger of better prognosis, and can as such be used in clinical practice to help characterize patients and, possibly, plan treatment and follow-up strategies.

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