Akila N. Viswanathan, MD
The use of computed-tomography (CT)-planned high-dose-rate (HDR) intracavitary brachytherapy (BT) demonstrated excellent local control (LC) and survival for patients with stage I/II cervical carcinoma, according to the results of a recent study published in Gynecologic Oncology
With a median follow-up of 30 months, no patients experienced local-only recurrence.
“We found that, of 9 patient characteristics and various RT prognostic factors tested in a univariate analysis, tumor size and total external beam radiation therapy (EBRT) plus BT dose were initially the most significant prognostic factors for predicting any recurrence (AR),” Akila N. Viswanathan, MD, executive vice chair, Johns Hopkins Radiation Oncology and Molecular Radiation Sciences, and her colleagues wrote in the study.
However, a bivariate model showed that total EBRT plus BT dose were no longer significant when adjusted for tumor size, the authors wrote. The authors of the study found large tumor size to be a prognostic factor for increased risk of recurrence outside the radiation field and worse progression-free survival (PFS) and overall survival (OS). Patients with tumors larger than 4 cm were 3 times more likely to develop regional or distant recurrence, compared with patients who had tumors ≤4 cm.
Moreover, the researchers also found that a volume-optimized plan treated a smaller area than a standard, Point A plan for these patients.
A total of 150 patients were treated for stage I/II cervical cancer using HDR CT-planned BT between April 2004 and October 2014 at Brigham and Women’s Hospital. One-hundred twenty-eight women met eligibility criteria for the current study, as they had stage I/II disease, were treated with CT-based BT, and were not treated with interstitial BT.
Patients were staged according to the International Federation of Gynecology and Obstetrics (FIGO) guidelines. Clinical examination reports provided information about tumor size, which was also subsequently confirmed using CT or MR. Small and large tumor size were defined as ≤4 cm and >4 cm, respectively.
For the BT procedure, patients were placed under general anesthesia and immobilized for applicator insertion, CT scanning, and treatment. A physician assessed the location, size, and firmness of residual disease at the time of brachytherapy. All contouring was performed by the treating physician, who also carried out the final treatment plan evaluation to maximize dose coverage and minimize dose to the organs at risk (OAR) (bladder, rectum, and sigmoid). Contouring per previously published guidelines included a clinical tumor volume (CTV) that encompassed the palpable disease, the contoured cervix to at least a height of approximately 3 cm along the tandem and laterally to the edge of the visualized cervix and parametrial regions. Point A was recorded, but not used for dose specification.
Pelvic recurrence sites were classified as either “true pelvis” (cervix, uterine corpus, vagina, and parametria) or “pelvic nodes” (external and internal iliac, obturator, and perivesical nodes). Regional recurrence (RR) was defined as failure in the para-aortic and inguinal nodes. Distant recurrence (DR) was defined as metastasis outside of the loco-regional sites as evidenced through PET-CT or MRI.
The primary endpoints included PFS—defined as no evidence of disease progression after tumor biopsy, and subdivided into PFS true pelvis
(local control) and PFS pelvic nodes
(local and regional control, or pelvic control [PC])—and OS, which was defined as the period from the date of biopsy until the date of death from any cause.
Thirty-eight patients (30%) had stage I disease, while 90 women (70%) had stage II cervical cancer. The overall median tumor size at the time of diagnosis was 3.8 cm (range, 0-6 cm), with stage I tumors yielding a smaller median size (2.9 cm; range, 0-7.6 cm) than stage II tumors (4.0 cm; range, 0-10 cm). Lymph node involvement was recorded in 40 patients (31%), 32 of whom (80%) had stage II disease.
Chemotherapy was administered to 114 patients (89%) and mainly included a platinum-based regimen of concurrent cisplatin or carboplatin. At the earliest, BT began in the fourth week of EBRT and was delivered in a dedicated BT suite with CT imaging done immediately after insertion. A total of 630 fractions were analyzed, with each patient receiving a median of 5 fractions (range, 3-5). The median per-fraction prescription dose was 5.5 Gy (range, 5.0-7.0), and the median average of Point A (fraction 1) was 5.0 Gy (range, 2.9-9.0). The cumulative EBRT plus BT dose to 90% of the tumor volume (D90) in EQD2 was 83.7 (range, 66.7-114.7), and the median cumulative doses (Gy3) to 2cm3
(D2cc) were 75.1 Gy for bladder, 63.9 Gy for rectum, and 59.4 Gy for sigmoid.