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 Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional 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/m(2)). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring 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 Common Terminology Criteria for Adverse Events, version 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 cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% (P =.025). Cervical cancer 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=.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 cancer patients). Evaluation and limitation of the volume of bone marrow treated with pelvic IMRT is warranted in patients receiving concurrent chemotherapy.

Fig. 1

Hematologic toxicity in the RTOG 0418 study among patients with (A) cervical cancer treated with weekly cisplatin and (B) endometrial cancer treated with radiation therapy without weekly cisplatin. All hematologic toxicity included anemia, thrombocytopenia, neutropenia, leukopenia, and lymphopenia. Leukopenia included both total white blood cell and absolute neutrophil counts. (C) Number of weekly cisplatin cycles given to patients with cervical cancer.

Fig. 1

Hematologic toxicity in the RTOG 0418 study among patients with (A) cervical cancer treated with weekly cisplatin and (B) endometrial cancer treated with radiation therapy without weekly cisplatin. All hematologic toxicity included anemia, thrombocytopenia, neutropenia, leukopenia, and lymphopenia. Leukopenia included both total white blood cell and absolute neutrophil counts. (C) Number of weekly cisplatin cycles given to patients with cervical cancer.

Fig. 2

(A) Pelvic bone marrow (BM) was defined within the treatment field by using a computed tomography (CT)-density–based auto-contouring algorithm. (B) Examples of patients with a V40 = 19% (upper panel) and V40 = 59% (lower panel). (C) Distribution of dose-volume histogram parameters for all patients in the study.

Fig. 2

(A) Pelvic bone marrow (BM) was defined within the treatment field by using a computed tomography (CT)-density–based auto-contouring algorithm. (B) Examples of patients with a V40 = 19% (upper panel) and V40 = 59% (lower panel). (C) Distribution of dose-volume histogram parameters for all patients in the study.

Fig. 2

(A) Pelvic bone marrow (BM) was defined within the treatment field by using a computed tomography (CT)-density–based auto-contouring algorithm. (B) Examples of patients with a V40 = 19% (upper panel) and V40 = 59% (lower panel). (C) Distribution of dose-volume histogram parameters for all patients in the study.

Fig. 3

Rates of hematologic toxicity and leukopenia in patients with cervical cancer who have a V40 greater than or less than the median value (37%). p < 0.05 χ² test.