Hematologic Toxicity in RTOG 0418: A Phase 2 Study of Postoperative IMRT for Gynecologic Cancer

Abstract

Purpose Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in RTOG 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multi-institutional setting. Methods and Materials Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRT and weekly cisplatin (40 mg/m2). Pelvic bone marrow was defined within the treatment field by using a computed tomography–density–based auto-contouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by CTCAE v 3.0 criteria. Results Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical patients with a median percentage volume of > 37% who received 40 Gy (V40 > 37%), 75% had grade ≥ 2 HT compared with 40% of patients with a V40 ≤ 37% who had this grade (p = 0.025). Cervical patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥ 2 HT than did those with a dose of ≤ 34.2 Gy (74% vs. 43%, p = 0.049). Conclusions Pelvic IMRT with weekly cisplatin is associated with low rates of HT and high rates of weekly cisplatin use. The volume of bone marrow receiving 40 Gy and the median dose to bone marrow correlated with higher rates of grade ≥ 2 toxicity among patients receiving weekly cisplatin (cervical patients). Evaluation and limitation of the volume of bone marrow treated with pelvic IMRT is warranted in patients receiving concurrent chemotherapy.

Pelvic insufficiency fracture (PIF) incidence in patients treated with intensity-modulated radiation therapy (IMRT) for gynaecological or anal cancer: single-institution experience and review of the literature

“…Results: 341 patients were treated by IMRT for gynaecological or anal cancer between 2007 and 2014. 15 patients experienced at least 1 pelvic fracture after external beam radiotherapy, corresponding to an overall incidence of 4.4%. Age and menopausal status were correlated with an increased fracture risk (p 5 0.0274 and p , 0.0001, respectively).…”

“…Several dosimetric and clinical studies have demonstrated the benefit of this technique, especially for the treatment of concave volumes, as in the case of pelvic tumours. [13][14][15][16] Gynaecological and gastrointestinal tumours correspond to different treatment volumes and radiation doses, which may account for variations in the incidence of PIF.…”

Dosimetric Comparison of Intensity-Modulated Proton Therapy and Volumetric-Modulated Arc Therapy in Anal Cancer Patients and the Ability to Spare Bone Marrow

“…Among patients with cervical cancer with V40 . 37%, 75% had grade 2 or higher hematologic toxicity compared with 40% of patients with V40 , 37% [10]. As a result of these previously published studies, we selected mean bone marrow dose , 22.5 Gy, V10 , 90%, and V40 , 37% as bone marrow constraints for our comparative plans.…”

Rola badania PET w leczeniu raka szyjki macicy w doniesieniach na 3rd ESTRO Forum 2015

“…Następnie zastosowano leczenie radioterapeutyczne z oszczędzeniem tych rejonów. Dzięki temu spodziewany jest zysk w hematologicznej toksyczności podczas radiochemioterapii [21]. Toczy się także badanie RTOG 0418, które ma na celu zdefiniowanie obszarów z aktywnym szpikiem kostnym w obrębie miednicy.…”