International Journal of Radiation Oncology*Biology*Physics
Technological AdvancesInitial Report of Pencil Beam Scanning Proton Therapy for Posthysterectomy Patients With Gynecologic Cancer
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.
Section snippets
Methods and Materials
Posthysterectomy women diagnosed with gynecologic cancer and receiving proton radiation therapy were eligible for enrollment in our institutional review board–approved, prospective, image guided radiation therapy study. Patients with cervical or endometrial cancer underwent hysterectomy and bilateral salphingo-oophorectomy with or without lymph node dissection. One patient with vaginal cancer had previously undergone hysterectomy for benign reasons. All patients had baseline hematologic
Results
A total of 11 patients were included in the present analysis. The patient and treatment characteristics are summarized in Table 1. All patients completed the intended course of therapy. Two patients received IMRT for 1 to 3 fractions as a component of their treatment because of proton down time. Two patients also required a boost to the pelvis. One patient with a history of a kidney transplant who had undergone radical hysterectomy required a boost to the right parametria for a positive
Discussion
We have demonstrated that proton therapy for posthysterectomy pelvic radiation therapy using PBS is well tolerated with acceptable rates of acute hematologic, gastrointestinal, and genitourinary toxicity. We observed that increased sparing of OARs is possible with PBS compared with IMRT in low-dose regions. However, at some dose levels >30 to 40 Gy for the PBM, rectum, and/or bowel, IMRT was superior to PBS. In particular, increased sparing of the total PBM and small and large bowel was noted
Conclusions
We have reported our initial clinical experience with pencil beam proton therapy for women with gynecologic malignancies after hysterectomy. Our study has demonstrated that PBS could be superior to IMRT for OAR sparing, in particular for the bone marrow, with target coverage that is robust relative to the setup uncertainties in this population and low rates of acute toxicities. Additional follow-up data are needed to assess the late toxicities and clinical outcomes associated with PBS. Future
Acknowledgments
The authors wish to acknowledge Dr Edgar Ben-Joseph for his helpful review of our report.
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Conflict of interest: L. L. Lin has received a grant from Varian Medical Systems for work unrelated to this report. The remaining authors have no conflicts.