Faculty Bibliography

PURPOSE AND METHODS/OBJECTIVE:The advent of affordable and rapid next-generation DNA sequencing technology, along with the US Supreme Court ruling invalidating gene patents, has led to a deluge of germline and tumor genetic variant tests that are being rapidly incorporated into clinical cancer decision making. A major concern for clinicians is whether the presence of germline mutations may increase the risk of radiation toxicity or secondary malignancies. Since minimal clinical data exist to inform decisions at this time, the American Society for Radiation Oncology (ASTRO) convened a group of radiation science experts and clinicians to summarize potential issues, review relevant data, and provide guidance for adult patients and their care teams regarding the impact, if any, that genetic testing should have on radiation therapy recommendations. RESULTS AND CONCLUSIONS/CONCLUSIONS:During the ASTRO Workshop, several main points emerged, which are discussed in this manuscript: 1) Variants of uncertain significance should be considered non-deleterious until functional genomic data emerges to demonstrate otherwise; 2) Possession of germline alterations in a single copy of a gene critical for radiation damage responses does not necessarily equate to increased risk of radiation-induced toxicity; 3) Deleterious ATM mutations may modestly increase second cancer risk after radiotherapy, thus follow-up for these patients after indicated radiotherapy should include second cancer screening; 4) Conveying to patients the difference between relative and absolute risk is critical to decision making; and 5) More work is needed to assess the impact of tumor somatic alterations on the probability of response to radiotherapy and the potential for individualization of radiation doses. Data on radiosensitivity related to specific genetic mutations is also briefly discussed.

Purpose: Radiation induced interstitial pneumonitis and late renal dysfunction are major concerns for patients undergoing total body irradiation (TBI). The purpose of this work is to evaluate the dosimetry of VMAT-based TBI plans generated using Varian Eclipse scripting.
Method(s): Three full-body CT datasets (two patients, one anthropomorphic CIRS phantom) were used. An in-house Eclipse script was developed to generate optimized field arrangements using the body contour, user origin, and couch longitudinal travel. Plans consisted of a lower-body AP/PA portion and an upper-body VMAT portion (8 full arcs with 4-isocenters). Treatment plans to 1320 cGy (165 cGy x 8fx) were generated with dose directives: [PTV V100% >=90- 95%; Total lung Dmean <900 cGy; Kidneys Dmean <1100 cGy]. All plans used 6MV photons and were calculated using the AAA algorithm. Upperbody VMAT plan dosimetry was evaluated 'in-phantom' placing 12 OSLDs in different key locations (lung, kidneys, bone, and soft tissue). Additionally, dosimetric verification was performed for the three plans using Varian portal dosimetry, PerFraction(SNC) and ArcCheck(SNC) with a global gamma criterion of 2%/2 mm.
Result(s): Planning objectives were met for the three treatment plans with the following averages: PTV V100% = 94.02%, total lung Dmean = 872.9 cGy, and kidneys Dmean = 1075.8 cGy. The dose deviation between Eclipse and the OSLDs (relative to the prescribed dose) averaged 0.98%, with each individual dose deviation within +/-4%. Dose ranged between 52.5 cGy (lung) and 187.5 cGy (bone) for OSLD measurements. The average passing rate for all 24 fields (8 per plan) was 98.0%, 99.76% and 98.6% for portal dosimetry, PerFraction and ArcCheck respectively. The lowest passing rate of any individual field was 95.4%, 99.0% and 91.8% for portal dosimetry, PerFraction and ArcCheck respectively.
Conclusion(s): Eclipse scripting can assist in creating robust multi-isocentric VMATbased TBI treatment plans to block lungs and kidneys without compromising target coverage. Dosimetric accuracy and deliverability was confirmed using in-phantom OSLD dosimetry, Varian portal dosimetry, PerFraction and Arc-Check verification

The therapeutic management of regional lymph nodes in breast cancer has seen a remarkable change in the past 2 decades. Clinical trials have refined our knowledge regarding the biology of the disease including the prognostic significance of disease in the regional lymph nodes. The contemporary management of lymph nodes is also influenced by advances in surgical technique, radiation oncology delivery systems, and effective systemic therapy regimens. This paper describes the role of regional nodal irradiation in the context of the de-escalation of axillary surgery, improved understanding of the molecular and pathologic features, and increasing use of neoadjuvant chemotherapy.