A Fifteen‐Gene Classifier to Predict Neoadjuvant Chemotherapy Responses in Patients with Stage IB to IIB Squamous Cervical Cancer

Purpose We compared the efficacy and toxicity of neoadjuvant chemotherapy followed by radical surgery versus standard cisplatin-based chemoradiation in patients with locally advanced squamous cervical cancer. Patients and Methods This was a single-center, phase III, randomized controlled trial ( ClinicalTrials.gov identifier: NCT00193739). Eligible patients were between 18 and 65 years old and had stage IB2, IIA, or IIB squamous cervical cancer. They were randomly assigned, after stratification by stage, to receive either three cycles of neoadjuvant chemotherapy using paclitaxel and carboplatin once every 3 weeks followed by radical hysterectomy or standard radiotherapy with concomitant cisplatin once every week for 5 weeks. Patients in the neoadjuvant group received postoperative adjuvant radiation or concomitant chemotherapy and radiotherapy, if indicated. The primary end point was disease-free survival (DFS), defined as survival without relapse or death related to cancer, and secondary end points included overall survival and toxicity. Results Between September 2003 and February 2015, 635 patients were randomly assigned, of whom 633 (316 patients in the neoadjuvant chemotherapy plus surgery group and 317 patients in the concomitant chemoradiation group) were included in the final analysis, with a median follow-up time of 58.5 months. The 5-year DFS in the neoadjuvant chemotherapy plus surgery group was 69.3% compared with 76.7% in the concomitant chemoradiation group (hazard ratio, 1.38; 95% CI, 1.02 to 1.87; P = .038), whereas the corresponding 5-year OS rates were 75.4% and 74.7%, respectively (hazard ratio, 1.025; 95% CI, 0.752 to 1.398; P = .87). The delayed toxicities at 24 months or later after treatment completion in the neoadjuvant chemotherapy plus surgery group versus the concomitant chemoradiation group were rectal (2.2% v 3.5%, respectively), bladder (1.6% v 3.5%, respectively), and vaginal (12.0% v 25.6%, respectively). Conclusion Cisplatin-based concomitant chemoradiation resulted in superior DFS compared with neoadjuvant chemotherapy followed by radical surgery in locally advanced cervical cancer.

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Comparative study of chemoradiation and neoadjuvant chemotherapy effects before radical hysterectomy in stage IB–IIB bulky cervical cancer and with tumor diameter greater than 4 cm

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200505000-00011 ◽

2005 ◽

Vol 15 (3) ◽

pp. 483-488

Author(s):

M. Modarress ◽

F. Q. Maghami ◽

M. Golnavaz ◽

N. Behtash ◽

A. Mousavi ◽

...

Keyword(s):

Cervical Cancer ◽

Neoadjuvant Chemotherapy ◽

Radical Hysterectomy ◽

Tumor Size ◽

Pathologic Complete Response ◽

Residual Tumor ◽

Preoperative Treatment ◽

Tumor Diameter ◽

Stage Ib ◽

Significant Difference

Tumor size seems to be a determinant in the prognosis of early cervical cancer. Patients with tumor greater than 4 cm (bulky) in diameter have worse outcome. The purpose of this study was to compare the efficacy of preoperative combined chemoradiation and neoadjuvant chemotherapy (NAIC) programs followed by radical hysterectomy in stage IB–IIB bulky cervical cancer. From September 1999 to April 2002, 60 patients with stage IB–IIB bulky cervical cancer were treated with preoperative external-beam radiotherapy to 45 Gy plus weekly cisplatin 50 mg/m2 or preoperative NAIC by cisplatin 50 mg/m2 and vincristin 1 mg/m2 every 7–10 days, for three courses. Surgery was performed 4–6 weeks after the completion of the preoperative treatment. There were no significant difference between age, stage, tumor size, and histopathologic type in two groups (P > 0.05). Toxicity associated with two treatment methods was usually mild. In chemoradiation group, two patients developed vesicovaginal fistula, and four patients developed long-term hydronephrosis that needed urethral stenting. Before surgery, complete and partial clinical response had no significant difference between two groups (P > 0.05). After surgery, lymph node and parametrial involvement had no significant difference between two groups (P > 0.05). In NAIC group, more patients had significantly residual tumor (P = 0.012), but residual tumor size had no significant difference between two groups (P > 0.05). Pathologic complete response was significantly higher in chemoradiation group (P = 0.004). According to the result of this study, it seems that NAIC and chemoradiation had similar effects in survival prognostic factors.

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Neoadjuvant chemotherapy followed by surgery has no therapeutic advantages over concurrent chemoradiotherapy in International Federation of Gynecology and Obstetrics stage IB-IIB cervical cancer

Journal of Gynecologic Oncology ◽

10.3802/jgo.2016.27.e52 ◽

2016 ◽

Vol 27 (5) ◽

Cited By ~ 9

Author(s):

Jeongshim Lee ◽

Tae Hyung Kim ◽

Gwi Eon Kim ◽

Ki Chang Keum ◽

Yong Bae Kim

Keyword(s):

Cervical Cancer ◽

Neoadjuvant Chemotherapy ◽

Concurrent Chemoradiotherapy ◽

International Federation ◽

Stage Ib ◽

Gynecology And Obstetrics

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Neoadjuvant chemotherapy followed by chemoradiation in selected locally advanced squamous cervical cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5603 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5603-5603

Author(s):

Juan Fernando Cueva ◽

Nieves Martinez Lago ◽

Maria Vieito ◽

Ezequiel Gonzalez Patino ◽

Maria Teresa Curiel Garcia ◽

...

Keyword(s):

Cervical Cancer ◽

Neoadjuvant Chemotherapy ◽

Response Rate ◽

Locally Advanced ◽

Dose Intensity ◽

Progression Free Survival ◽

Definitive Treatment ◽

Disease Response ◽

Squamous Cervical Cancer ◽

Weekly Cisplatin

5603 Background: Although there has not been a direct comparison between neoadjuvant chemotherapy followed by chemoradiation with chemoradiation alone, neoadjuvant chemotherapy is active in squamous cervical cancer. Methods: In this one arm phase II trial we accrued 25 patients from 2007 to 2012 diagnosed with squamous cervical cancer deemed poor candidates to initial chemoradiation (decided by a multidisciplinary committee). Patients had > 18 years of age, PS 0-1, adequate organ function an gave informed consent. They received neoadjuvant paclitaxel and cisplatin (80 and 33 mg/m2 respectively) on days 1,7, 15 of every 28 for two cycles and then external radiation in 1.8 Gy/ fraction with concurrent weekly cisplatin 40 mg/m2followed by brachytherapy in 5-6 applications. Dose intensity and toxicity was accrued, and both after neoadjuvant and chemoradiation patients were evaluated by RECIST 1.1 criteria for response with CT scan and pelvic MNR. Results: Baseline characteristics of the patients are listed in Table. 24 patients were evaluable for efficacy and safety. Response rate after neoadjuvant chemotherapy was 84 % (complete and partial responses in 24 and 60% of patients, respectively), without progression disease. Response rate after radiochemotherapy was 93 % (complete and partial responses in 52 and 41% of patients, respectively). After a mean of 29 months of follow up, 11 patients (45%) thus far have developed recurrent disease. Median progression-free survival and overall survival were 33 (23- 42) and 34+ m (29 – not reached). Treatment was well tolerated, without toxicities grade 3-4. Conclusions: Our weekly cisplatin-paclitaxel neoadjuvant regimen has been feasible and very effective in terms of dose delivery, tolerance and radiological responses without compromising definitive treatment with chemoradiation. If this approach is superior than the standard chemoradiation alone in this population should be explored in a randomized trial. [Table: see text]

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Single-dose intra-arterial neoadjuvant chemotherapy while waiting for radical hysterectomy for stage IB-IIB cervical cancer

Molecular and Clinical Oncology ◽

10.3892/mco.2016.846 ◽

2016 ◽

Vol 4 (6) ◽

pp. 1068-1072 ◽

Cited By ~ 1

Author(s):

KIYOSHI YOSHINO ◽

AYAKO HOSOI ◽

KEIGO OSUGA ◽

TAKAYUKI ENOMOTO ◽

YUTAKA UEDA ◽

...

Keyword(s):

Cervical Cancer ◽

Single Dose ◽

Neoadjuvant Chemotherapy ◽

Radical Hysterectomy ◽

Stage Ib

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Perioperative treatments for stage IB–IIB uterine cervical cancer

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyz200 ◽

2019 ◽

Vol 50 (2) ◽

pp. 99-103

Author(s):

Muneaki Shimada ◽

Hideki Tokunaga ◽

Hiroaki Kobayashi ◽

Mitsuya Ishikawa ◽

Nobuo Yaegashi

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Neoadjuvant Chemotherapy ◽

Radical Hysterectomy ◽

Adjuvant Radiotherapy ◽

Concurrent Chemoradiotherapy ◽

Risk Groups ◽

Perioperative Chemotherapy ◽

Stage Ib ◽

Risk Patients

Abstract Japan Society of Gynecologic Oncology guidelines recommended either radical hysterectomy-based approach or the definitive radiotherapy including concurrent chemoradiotherapy as primary treatment for patients with not only stage IB1/IIA1, but also stages IB2, IIA2 and IIB. Based on pathological findings of surgical specimens, patients who underwent radical hysterectomy are divided into three recurrent-risk groups, low-risk, intermediate, and high-risk groups. Although some authors reported the usefulness of adjuvant chemotherapy for intermediate/high-risk patients, radiotherapy was standard adjuvant treatment for pathological-risk patients after radical hysterectomy. It has been uncertain whether neoadjuvant chemotherapy followed by radical hysterectomy is beneficial for stage IB2–IIB patients. Recently, the randomized phase III study revealed that neoadjuvant chemotherapy followed by radical hysterectomy failed to improve survival of stage IB2–IIB patients compared to concurrent chemoradiotherapy. Majority of stage IB2–IIB patients are required adjuvant radiotherapy after radical hysterectomy. The multimodality strategy consisting of radical hysterectomy followed by adjuvant radiotherapy is associated with not only impaired quality of life, but also conflicting of cost-effectiveness. Thereby, some authors investigated the significance of multimodality strategy consisting of chemotherapy before/after radical hysterectomy for stage IB2–IIB cervical cancer. Multimodality strategy consisting of radical hysterectomy/perioperative chemotherapy needs higher curability of radical hysterectomy, higher response to perioperative chemotherapy and less perioperative complications. Consequently, gynecologic oncologists have to examine the patients strictly before treatment and judge whether radical hysterectomy-based approach or definitive irradiation is appropriate for the patient with stage IB–IIB cervical cancer.

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