Medical Physics Practice Guideline (MPPG) 11.a: Plan and chart review in external beam radiotherapy and brachytherapy.

A therapeutic medical physicist is responsible for reviewing radiation therapy treatment plans and patient charts, including initial treatment plans and new chart review, on treatment chart (weekly) review, and end of treatment chart review for both external beam radiation and brachytherapy. Task group report TG 275 examined this topic using a risk-based approach to provide a thorough analysis and guidance for best practice. Considering differences in resources and workflows of various clinical practice settings, the Professional Council of the American Association of Physicists in Medicine assembled this task group to develop a practice guideline on the same topic to provide a minimum standard that balances an appropriate level of safety and resource utilization. This medical physics practice guidelines (MPPG) thus provides a concise set of recommendations for medical physicists and other clinical staff regarding the review of treatment plans and patient charts while providing specific recommendations about who to be involved, and when/what to check in the chart review process. The recommendations, particularly those related to the initial plan review process, are critical for preventing errors and ensuring smooth clinical workflow. We believe that an effective review process for high-risk items should include multiple layers with collective efforts across the department. Therefore, in this report, we make specific recommendations for various roles beyond medical physicists. The recommendations of this MPPG have been reviewed and endorsed by the American Society of Radiologic Technologists and the American Association of Medical Dosimetrists.

Organ sparing of linac-based targeted marrow irradiation over total body irradiation.

PURPOSE: Targeted marrow irradiation (TMI) is an alternative conditioning regimen to total body irradiation (TBI) before bone marrow transplantation in hematologic malignancies. Intensity-modulation methods of external beam radiation therapy are intended to permit significant organ sparing while maintaining adequate target coverage, improving the therapeutic ratio. This study directly compares the dose distributions to targets and organs at risk from TMI and TBI, both modalities conducted by general-use medical linacs at our institution. METHODS: TMI treatments were planned for 10 patients using multi-isocentric feathered volumetric arc therapy (VMAT) plans, delivered by 6 MV photon beams of Elekta Synergy linacs. The computed tomography (CT) datasets used to obtain these plans were also used to generate dose distributions of TBI treatments given in the AP/PA extended-field method. We compared dose distributions normalized to the same prescription for both plan types. The generalized equivalent uniform dose (gEUD) of Niemierko for organs and target volumes was used to quantify effective whole structure dose and dose savings. RESULTS: For the clinical target volume (CTV), no significant differences were found in mean dose or gEUD, although the radical dose homogeneity index (minimum dose divided by maximum dose) was 31.7% lower (P = 0.002) and the standard deviation of dose was 28.0% greater (P = 0.027) in the TMI plans than in the TBI plans. For the TMI plans, gEUD to the lungs, brain, kidneys, and liver was significantly lower (P < 0.001) by 47.8%, 33.3%, 55.4%, and 51.0%, respectively. CONCLUSION: TMI is capable of maintaining CTV coverage as compared to that achieved in TBI, while significantly sparing organs at risk. Improvement on sparing organs at risk permits a higher prescribed dose to the target or the maximum number of times marrow conditioning may be delivered to a patient while maintaining similar typical tissue complication rates.

Real-time in vivo dosimetry for SBRT prostate treatment using plastic scintillating dosimetry embedded in a rectal balloon: a case study.

A novel FDA approved in vivo dosimetry device system using plastic scintillating detectors placed in an endorectal balloon to provide real-time in vivo dosimetry for prostatic rectal interface was tested for use with stereotactic body radiotherapy (SBRT). The system was used for the first time ever to measure dose during linear accelerator based SBRT. A single patient was treated with a total dose of 36.25 Gy given in 5 fractions. Delivered dose was measured for each treatment with the detectors placed against the anterior rectal wall near the prostate rectal interface. Measured doses showed varying degrees of agreement with computed/ planned doses, with average combined dose found to be within 6% of the expected dose. The variance between measurements is most likely due to uncertainty of the detector location, as well as variation in the placement of a new balloon prior to each fraction. Distance to agreement for the detectors was generally found to be within a few millimeters, which also suggested that the differences in measured and calculated doses were due to positional uncertainty of the detectors during the SBRT, which had sharp dose falloff near the penumbra along the rectal wall. Overall, the use of a real time in vivo dosimeter provided a level of safety and improved confidence in treatment delivery. We are evaluating the device further in an IRB-approved prospective partial prostate SBRT trial, and believe further clinical investigations are warranted.

Absolute calibration of optical power for PDT: report of AAPM TG140.

This report is primarily concerned with methods for optical calibration of laser power for continuous wave (CW) light sources, predominantly used in photodynamic therapy (PDT). Light power calibration is very important for PDT, however, no clear standard has been established for the calibration procedure nor the requirements of power meters suitable for optical power calibration. The purposes of the report are to provide guidance for establishing calibration procedures for thermopile type power meters and establish calibration uncertainties for most commercially available detectors and readout assemblies. The authors have also provided a review of the use of various power meters for CW and pulsed optical sources, and provided recommended temporal frequencies for optical power meter calibrations and guidance for routine quality assurance procedure.

Radiosensitization of human cervical cancer cells by inhibiting ribonucleotide reductase: enhanced radiation response at low-dose rates.

PURPOSE: To test whether pharmacologic inhibition of ribonucleotide reductase (RNR) by 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) enhances radiation sensitivity during low-dose-rate ionizing radiation provided by a novel purpose-built iridium-192 cell irradiator. METHODS AND MATERIALS: The cells were exposed to low-dose-rate radiation (11, 23, 37, 67 cGy/h) using a custom-fabricated cell irradiator or to high-dose-rate radiation (330 cGy/min) using a conventional cell irradiator. The radiation sensitivity of human cervical (CaSki, C33-a) cancer cells with or without RNR inhibition by 3-AP was evaluated using a clonogenic survival and an RNR activity assay. Alteration in the cell cycle distribution was monitored using flow cytometry. RESULTS: Increasing radiation sensitivity of both CaSki and C33-a cells was observed with the incremental increase in radiation dose rates. 3-AP treatment led to enhanced radiation sensitivity in both cell lines, eliminating differences in cell cytotoxicity from the radiation dose rate. RNR blockade by 3-AP during low-dose-rate irradiation was associated with low RNR activity and extended G(1)-phase cell cycle arrest. CONCLUSIONS: We conclude that RNR inhibition by 3-AP impedes DNA damage repair mechanisms that rely on deoxyribonucleotide production and thereby increases radiation sensitivity of human cervical cancers to low-dose-rate radiation.

Preliminary clinical and pharmacologic investigation of photodynamic therapy with the silicon phthalocyanine photosensitizer pc 4 for primary or metastatic cutaneous cancers.

Photodynamic therapy (PDT) for cutaneous malignancies has been found to be an effective treatment with a range of photosensitizers. The phthalocyanine Pc 4 was developed initially for PDT of primary or metastatic cancers in the skin. A Phase I trial was initiated to evaluate the safety and pharmacokinetic profiles of systemically administered Pc 4 followed by red light (Pc 4-PDT) in cutaneous malignancies. A dose-escalation study of Pc 4 (starting dose 0.135 mg/m(2)) at a fixed light fluence (135 J/cm(2) of 675-nm light) was initiated in patients with primary or metastatic cutaneous malignancies with the aim of establishing the maximum tolerated dose (MTD). Blood samples were taken at intervals over the first 60 h post-PDT for pharmacokinetic analysis, and patients were evaluated for toxicity and tumor response. A total of three patients (two females with breast cancer and one male with cutaneous T-cell lymphoma) were enrolled and treated over the dose range of 0.135 mg/m(2) (first dose level) to 0.54 mg/m(2) (third dose level). Grade 3 erythema within the photoirradiated area was induced in patient 2, and transient tumor regression in patient 3, in spite of the low photosensitizer doses. Pharmacokinetic observations fit a three-compartment exponential elimination model with an initial rapid distribution phase (∼0.2 h) and relatively long terminal elimination phase (∼28 h), Because of restrictive exclusion criteria and resultant poor accrual, the trial was closed before MTD could be reached. While the limited accrual to this initial Phase I study did not establish the MTD nor establish a complete pharmacokinetic and safety profile of intravenous Pc 4-PDT, these preliminary data support further Phase I testing of this new photosensitizer.

Silicon phthalocyanine (Pc 4) photodynamic therapy is a safe modality for cutaneous neoplasms: results of a phase 1 clinical trial.

BACKGROUND: Photodynamic therapy (PDT) is a non-invasive treatment for non-melanoma skin cancer. However, PDT systems currently used clinically have limitations such as pain and superficial tissue penetration. The silicon phthalocyanine Pc 4 is a second-generation photosensitizer with peak absorption in the far red at 675 nm. OBJECTIVE: To assess the safety and tolerability of topically applied Pc 4 followed by red light (Pc 4-PDT) in treating cutaneous neoplasms. STUDY DESIGN/MATERIALS AND METHODS: Forty three adults with a diagnosis of neoplasms including actinic keratoses, Bowen's disease, squamous cell carcinoma, basal cell carcinoma, or mycosis fungoides were treated with a single administration of Pc 4-PDT and followed for 14 days. The study utilized a light and Pc 4 dose escalation design in sequential groups of three subjects each. RESULTS: Pc 4-PDT was well tolerated with no significant local toxicity or increased photosensitivity. It has promising biologic effects, particularly in mycosis fungoides where 14 of 35 subjects demonstrated a clinical response, which correlates with Pc 4-PDT-induced apoptosis, as measured by increased active caspase-3 in the treated skin lesions. CONCLUSIONS: Pc 4-PDT is a safe and tolerable treatment modality that effectively triggers apoptosis in cutaneous neoplasms such as mycosis fungoides.