Initial Report of Pencil Beam Scanning Proton Therapy for Posthysterectomy Patients With Gynecologic Cancer

Purpose

To report the acute toxicities associated with pencil beam scanning proton beam radiation therapy (PBS) for whole pelvis radiation therapy in women with gynecologic cancers and the results of a dosimetric comparison of PBS versus intensity modulated radiation therapy (IMRT) plans.

Methods and Materials

Eleven patients with posthysterectomy gynecologic cancer received PBS to the whole pelvis. The patients received a dose of 45 to 50.4 Gy relative biological effectiveness (RBE) in 1.8 Gy (RBE) daily fractions. Acute toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 4. A dosimetric comparison between a 2-field posterior oblique beam PBS and an IMRT plan was conducted. The Wilcoxon signed rank test was used to assess the potential dosimetric differences between the 2 plans and PBS target coverage robustness relative to setup uncertainties.

Results

The median patient age was 55 years (range 23-76). The primary site was cervical in 7, vaginal in 1, and endometrial in 3. Of the 11 patients, 7 received concurrent cisplatin, 1 each received sandwich carboplatin and paclitaxel chemotherapy, both sandwich and concurrent chemotherapy, and concurrent and adjuvant chemotherapy, and 1 received no chemotherapy. All patients completed treatment. Of the 9 patients who received concurrent chemotherapy, the rate of grade 2 and 3 hematologic toxicities was 33% and 11%, respectively. One patient (9%) developed grade 3 acute gastrointestinal toxicity; no patient developed grade ≥3 genitourinary toxicity. The volume of pelvic bone marrow, bladder, and small bowel receiving 10 to 30 Gy was significantly lower with PBS than with intensity modulated radiation therapy (P<.001). The target coverage for all PBS plans was robust relative to the setup uncertainties (P>.05) with the clinical target volume mean dose percentage received by 95% and 98% of the target volume coverage changes within 2% for the individual plans.

Conclusions

Our results have demonstrated the clinical feasibility of PBS and the dosimetric advantages, especially for the low-dose sparing of normal tissues in the pelvis with the target robustness maintained relative to the setup uncertainties. Future studies with larger patient numbers are planned to further validate our preliminary findings.

Introduction

Primary or adjuvant treatment for women with locally advanced gynecologic malignancies, including cervical and vaginal cancer, includes concurrent chemotherapy with pelvic and/or inguinal radiation therapy. For women with stage III or IV endometrial cancer, combined modality therapy in the adjuvant setting, including concurrent, sequential, or sandwich chemotherapy, is frequently used. The optimal delivery of chemotherapy can be limited by bone marrow suppression from both radiation therapy and chemotherapy (1). Several randomized studies have demonstrated an overall survival and locoregional control benefit by the addition of concurrent chemotherapy to radiation therapy in women with locally advanced cervical cancer 2, 3, 4. The inability to deliver all intended chemotherapy can result in inferior outcomes, which has been previously demonstrated 4, 5.

Normal tissue complication probability modeling studies have supported the hypothesis that hematologic toxicity increases with an increasing volume of pelvic bone marrow (PBM) irradiated (6). Strategies to limit the bone marrow dose using intensity modulated radiation therapy (IMRT) have been evaluated, with recent studies demonstrating that the volume of PBM receiving 10 and 20 Gy (V10, V20, respectively) is significantly associated with the development of acute hematologic toxicity in women receiving concurrent platinum-based chemotherapy 7, 8. One of the potential consequences of bone marrow sparing using IMRT is greater incidental doses to other organs at risk (OARs), because the beam angles and dose constraints chosen to avoid high doses to the bone marrow will result in consequently higher doses to other OARs (9).

The physical characteristics of protons allow for irradiation of the target with a minimal exit and integral dose, which might result in lower collateral irradiation to normal structures (ie, bone marrow, bowel) compared with IMRT 10, 11. Decreased bone marrow and bowel doses could allow intensifying combined modality therapy for women with gynecologic cancers.

Only recently has proton technology evolved to allow for efficient treatment of the whole pelvis with pencil beam scanning. Previously, proton delivery was largely confined to passive scattering, which requires multiple beams, is less conformal, and requires a longer treatment time (12). We report the first clinical experience, to the best of our knowledge, using pencil beam scanning proton therapy (PBS) for women in the posthysterectomy setting and a dosimetric comparison between a 2-field posterior oblique PBS proton technique routinely used in our clinic and IMRT.