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Robust Treatment Planning in Whole Pelvis Pencil Beam Scanning Proton Therapy for Prostate Cancer - Beyond the Abstract

With an estimated 191,930 new diagnoses in 2020,1 prostate adenocarcinoma is the most common non-cutaneous malignancy afflicting males in the United States. Primary management options for localized disease include watchful waiting, active surveillance, radiation therapy (RT) with or without androgen deprivation therapy (ADT), and radical prostatectomy (RP).2,3 If RP is pursued, the need for adjuvant or salvage RT and/or ADT is typically determined by post-operative pathologic features and biochemical trends.4,5


While an area of active investigation, definitive or post-operative RT can be delivered to the whole pelvis (WPRT) as opposed to the prostate gland or surgical bed alone. Given the current clinical equipoise, in the intact setting, RTOG 0924 is an ongoing Phase III trial that randomizes intermediate- and high-risk prostate cancer patients to prostate RT versus WPRT followed by external beam or brachytherapy boost with ADT. In the postoperative setting, RTOG 0534 is a three-arm Phase III trial of 1) prostate bed radiation (PBR) alone, 2) PBR + short term androgen deprivation (STAD), and 3) WPRT + STAD in patients with rising PSAs after RP. Interim findings of RTOG 0534 were presented at ASTRO 2018 with a median follow-up of 5.4 years and demonstrated a 16% and 6% improvement in freedom from progression in the WPRT+STAD arm compared to arms 1 and 2, respectively.6

WPRT has mostly been delivered with standard photon beams, as in the above trials. Limited evidence and technical descriptions have been reported regarding the use of proton therapy in such scenarios.7-10 Pencil beam scanning proton therapy (PBS) is increasingly becoming the preferred proton delivery modality due to its more conformal nature, larger treatment field size, lower neutron contamination dose, and reduced resource requirements.11 Given the particle’s distinct properties, robust planning techniques have been implemented at our institution to ensure the consistent delivery of high-quality proton therapy.

Two unique whole-pelvis PBS planning techniques, conventional optimization (CO) and robust optimization (RO), are described in this report. Conceptually, they represent different approaches to manage anatomic and delivery uncertainties. Logistically, the workflows differ in the employment of field-specific targets and coverage optimization.

Radiation Field Arrangements

WPRT PBS plans use isocentric opposed lateral fields and a posterior field. In CO plans, the superior portion is treated with the posterior field, and the inferior portion is treated with lateral fields. The fields are matched in an overlapping region with a superior-to-inferior dose gradient, improving robustness. In RO plans, there is no superior-inferior split. Instead, field-specific targets are used to avoid pencil beam delivery through organs at risk (OARs).

Conventional Optimization Workflow

To create matched fields, two pencil beam scanning target volumes (PBSTVsup and PBSTVinf) are created to define where the treatment planning system (TPS) places beam spots. The posterior field covers PBSTVsup, and the lateral fields cover PBSTVinf. These PBSTVs are expansions of the CTV, with differential margins to account for proton range uncertainty. The superior and inferior fields are optimized individually and then combined into a composite plan.

Robust Optimization Workflow

While CO optimizes individual fields independently, the RO workflow uses multi-field optimization (MFO) where all fields are optimized simultaneously to achieve uniform composite coverage. This theoretically enables superior OAR sparing and improved robustness as the entire target volume is treated by multiple fields. This requires field-specific targets with overlapping regions defining permissible limits for placement of pencil beams in the TPS. They are created by cropping the PTV to remove parts requiring treatment through OARs, except where the target itself overlaps OARs. This method of cropping field-specific targets avoids areas of greatest anatomic variation, theoretically improving robustness as well as OAR sparing.

RO can produce better quality plans,12 and the workflow is simpler as fields are optimized simultaneously and do not require the gradient structures in CO. Application of MFO can increase plan complexity through increased intensity modulation, but anatomic sources of uncertainty are avoided and robustness is theoretically superior. Finally, while not discussed in this report, RO also enables simultaneous integrated boosts of nodal volumes.

Conclusion

With growing evidence to support WPRT in the post-operative setting,6 the potential to reduce the integral dose and bowel exposure with pelvic PBS compared to IMRT,13,14 and the increasing availability of PBS proton therapy,15 this report offers a timely review of novel and relevant treatment planning techniques.

Two methods (CO and RO) for planning three-field whole-pelvis PBS cases for patients with prostate cancer have been presented. Both techniques create treatment plans with acceptable target coverage and OAR sparing. The field-specific targets used in RO plans theoretically allow for better OAR sparing and improved robustness by treating all parts of the target with multiple fields. CO can be implemented by institutions that do not have RO capabilities using the guide outlined in this report.

Written by: Anish A. Butala, MD and Neha Vapiwala, MD, Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

References:

  1. Siegel, Rebecca L., Kimberly D. Miller, and Ahmedin Jemal. "Cancer statistics, 2020." CA: A Cancer Journal for Clinicians 70, no. 1 (2020): 7-30.
  2. Bekelman, Justin E., R. Bryan Rumble, Ronald C. Chen, Thomas M. Pisansky, Antonio Finelli, Andrew Feifer, Paul L. Nguyen et al. "Clinically localized prostate cancer: ASCO clinical practice guideline endorsement of an American Urological Association/American Society for Radiation Oncology/Society of Urologic Oncology guideline." Journal of Clinical Oncology 36, no. 32 (2018): 3251-3258.
  3. Mohan, Ravinder, and Paul F. Schellhammer. "Treatment options for localized prostate cancer." American family physician 84, no. 4 (2011): 413-420.
  4. Pisansky, Thomas M., Ian M. Thompson, Richard K. Valicenti, Anthony V. D'Amico, and Shalini Selvarajah. "Adjuvant and salvage radiation therapy after prostatectomy: ASTRO/AUA guideline amendment, executive summary 2018." Practical radiation oncology 9, no. 4 (2019): 208-213.
  5. Pisansky, Thomas M., Ian M. Thompson, Richard K. Valicenti, Anthony V. D'Amico, and Shalini Selvarajah. "Adjuvant and Salvage Radiotherapy after Prostatectomy: ASTRO/AUA Guideline Amendment 2018-2019." The Journal of urology 202, no. 3 (2019): 533-538.
  6. Pollack, A., T. G. Karrison, A. G. Balogh, D. Low, D. W. Bruner, J. S. Wefel, L. G. Gomella et al. "Short term androgen deprivation therapy without or with pelvic lymph node treatment added to prostate bed only salvage radiotherapy: the NRG oncology/RTOG 0534 SPPORT trial." International Journal of Radiation Oncology• Biology• Physics 102, no. 5 (2018): 1605.
  7. Chera, Bhishamjit S., Carlos Vargas, Christopher G. Morris, Debbie Louis, Stella Flampouri, Daniel Yeung, Srividya Duvvuri, Zuofeng Li, and Nancy Price Mendenhall. "Dosimetric study of pelvic proton radiotherapy for high-risk prostate cancer." International Journal of Radiation Oncology* Biology* Physics 75, no. 4 (2009): 994-1002.
  8. Chuong, Michael D., William Hartsell, Gary Larson, Henry Tsai, George E. Laramore, Carl J. Rossi, J. Ben Wilkinson, Adeel Kaiser, and Carlos Vargas. "Minimal toxicity after proton beam therapy for prostate and pelvic nodal irradiation: results from the proton collaborative group REG001-09 trial." Acta Oncologica 57, no. 3 (2018): 368-374.
  9. Deville Jr, Curtiland, Akansha Jain, Wei-Ting Hwang, Kristina D. Woodhouse, Stefan Both, Shiyu Wang, Peter E. Gabriel et al. "Initial report of the genitourinary and gastrointestinal toxicity of post-prostatectomy proton therapy for prostate cancer patients undergoing adjuvant or salvage radiotherapy." Acta Oncologica 57, no. 11 (2018): 1506-1514.
  10. Widesott, Lamberto, Alessio Pierelli, Claudio Fiorino, Antony J. Lomax, Maurizio Amichetti, Cesare Cozzarini, Martin Soukup et al. "Helical tomotherapy vs. intensity-modulated proton therapy for whole pelvis irradiation in high-risk prostate cancer patients: dosimetric, normal tissue complication probability, and generalized equivalent uniform dose analysis." International Journal of Radiation Oncology* Biology* Physics 80, no. 5 (2011): 1589-1600.
  11. Deville, Curtiland, Matthew Ladra, Huifang Zhai, Moe Siddiqui, Stefan Both, and Haibo Lin. "Sarcoma." In Target Volume Delineation and Treatment Planning for Particle Therapy, pp. 347-367. Springer, Cham, 2018.
  12. Stützer, Kristin, Alexander Lin, Maura Kirk, and Liyong Lin. "Superiority in robustness of multifield optimization over single-field optimization for pencil-beam proton therapy for oropharynx carcinoma: an enhanced robustness analysis." International Journal of Radiation Oncology* Biology* Physics 99, no. 3 (2017): 738-749.
  13. Hashimoto, Shingo, Yuta Shibamoto, Hiromitsu Iwata, Hiroyuki Ogino, Hiroki Shibata, Toshiyuki Toshito, Chikao Sugie, and Jun-etsu Mizoe. "Whole-pelvic radiotherapy with spot-scanning proton beams for uterine cervical cancer: a planning study." Journal of radiation research 57, no. 5 (2016): 524-532.
  14. Colaco, Rovel J., Romaine Charles Nichols, Soon Huh, Nataliya Getman, Meng Wei Ho, Zuofeng Li, Christopher G. Morris, William M. Mendenhall, Nancy P. Mendenhall, and Bradford S. Hoppe. "Protons offer reduced bone marrow, small bowel, and urinary bladder exposure for patients receiving neoadjuvant radiotherapy for resectable rectal cancer." Journal of gastrointestinal oncology 5, no. 1 (2014): 3.
  15. Leeman, Jonathan E., Paul B. Romesser, Ying Zhou, Sean McBride, Nadeem Riaz, Eric Sherman, Marc A. Cohen, Oren Cahlon, and Nancy Lee. "Proton therapy for head and neck cancer: expanding the therapeutic window." The Lancet Oncology 18, no. 5 (2017): e254-e265.
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