Concurrent Chemoradiotherapy for Stage IIIB Cervical Cancer—Global Impact Through Power

Abstract

Of the 500 000 new cervical cancer cases annually, most (85%) locally advanced cervical cancer (LACC) occurs in low-and middle-income countries (LMICs), where sufficient resources are not always readily available for treatment. 1 For almost 2 decades, the optimal management for all LACC in the United States has included concurrent chemoradiotherapy (CRT). A National Cancer Institute 2 alert was released in 1999, after the publication of multiple randomized clinical trials demonstrated improved survival rates with concurrent CRT compared with radiotherapy (RT) alone. In particular, the Radiation Therapy Oncology Group (RTOG) 90-01 trial 3 showed a 5-year absolute survival benefit of 21% for all stages of cervical cancer with CRT. However, an unplanned and inadequately powered subgroup analysis of patients with stage III to IVA disease showed an overall survival (OS) advantage of 14% (P = .06), disease-free survival (DFS) benefit of 17% (P = .05), and locoregional control benefit of 15% (P = .065). 3 A 2010 meta-analysis 4 demonstrated a 5-year absolute OS benefit of 6% for all stages of cervical cancer treated with concurrent CRT compared with RT alone; however, the survival benefit was only 3% for women with stage III to IVA cervical cancer. Nevertheless, due to the lack of statistical significance in the patient subgroup with stage IIIB to IVA disease in RTOG 90-01, combined with issues of cost and access, some LMICs chose not to standardize CRT for all patients with LACC.The importance of statistical power (ie, having sufficient number of patients to show a benefit) is clearly demonstrated in the trial by Shrivastava et al 5 in this issue of JAMA Oncology. Their study is remarkable because it addresses this important global clinical dilemma and provides sufficient power in a subgroup of patients. This not only is one of the largest studies on LACC overall but also is the only study with sufficient numbers of patients to report conclusive randomized trial evidence for CRT in the stage IIIB subgroup. The study, conducted in Mumbai, India, at Tata Memorial Hospital, a high-volume government-directed cancer treatment institution, randomized women to receive external beam RT (50 Gy in 25 fractions) with brachytherapy alone or in combination with weekly cisplatin chemotherapy (40 mg/m 2 ). The trial results show detailed patient information, good treatment compliance, and reasonable long-term follow-up. The authors were able to achieve high chemotherapy compliance in the CRT arm (approximately 70%), delivered optimal treatment time in both arms (<56 days), and provided toxicity management. The results of the study are encouraging, with significant improvement in DFS and OS in patients treated with CRT compared with RT alone, with 5-year absolute DFS and OS benefit of 9% and 8%, ARTICLE INFORMATION

Different prognosis of stage IIIB cervical cancer patients with lower third of vaginal invasion and those without

“…At present, several articles have evaluated the prognostic factors of cervical cancer in stage IIIB, including the total treatment time, thromboembolism, neoadjuvant intra-arterial chemotherapy, pretreatment anemia, hydronephrosis, etc. [9][10][11][12][13][14][15][16]. However, there was only one study assessing the relationship between the invasion into the lower third part of the vagina and the prognosis of patients with stage IIIB cervical cancer.…”

Single Radiotherapy Fraction with Local Anti-CD40 Therapy Generates Effective Abscopal Responses in Mouse Models of Cervical Cancer

“…Combined radiotherapy regimens offer maximal local control of cancerous lesions, while sparing the healthy tissues and extending the survival of patients [1,7]. However, for most women in LMIC and other resource-poor settings who are disproportionately affected and diagnosed at an advanced stage, socio-economic barriers influence patient compliance with many fractions of radiotherapy and/or chemotherapy [8,9]. More accessible therapeutic approaches are needed for many patients with advanced disease.…”