Fetal dose assessment in a pregnant patient with brain tumor: A comparative study of proton PBS and 3DCRT/VMAT radiation therapy techniques.

PURPOSE: The treatment of brain tumors in pregnant patients poses challenges, as the out-of-field dose exposure to the fetus can potentially be harmful. A pregnant patient with prior radiation treatment was presented with a brain tumor at our clinic. This work reports on our pre-treatment study that compared fetal dose exposure between intensity-modulated proton therapy (IMPT) using pencil beam scanning (PBS) and conventional photon 3D conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT), and the subsequent pregnant patient's radiation treatment. MATERIALS AND METHODS: Pre-treatment measurements of clinical plans, 3DCRT, VMAT, and IMPT, were conducted on a phantom. Measurements were performed using a device capable of neutron detections, closely following AAPM guidelines, TG158. For photon measurements, fetus shielding was utilized. On patient treatment days, which was determined to be proton treatment, shielding was used only during daily imaging for patient setup. Additionally, an in vivo measurement was conducted on the patient. RESULTS: Measurements showed that IMPT delivered the lowest fetal dose, considering both photon and neutron out-of-field doses to the fetus, even when shielding was implemented for photon measurements. Additionally, the proton plans demonstrated superior treatment for the mother, a reirradiation case. CONCLUSION: The patient was treated with proton therapy, and the baby was subsequently delivered at full term with no complications. This case study supports previous clinical findings and advocates for the expanded use of proton therapy in this patient population.

Chest wall toxicity after hypofractionated proton beam therapy for liver malignancies.

PURPOSE: Normal liver-sparing with proton beam therapy (PBT) allows for dose escalation in the treatment of liver malignancies, but it may result in high doses to the chest wall (CW). CW toxicity (CWT) data after PBT for liver malignancies are limited, with most published reports describing toxicity after a combination of hypofractionated proton and photon radiation therapy. We examined the incidence and associated factors for CWT after hypofractionated PBT for liver malignancies. METHODS AND MATERIALS: We retrospectively reviewed the charts of 37 consecutive patients with liver malignancies (30 hepatocellular carcinoma, 6 intrahepatic cholangiocarcinoma, and 1 metastasis) treated with hypofractionated PBT. CWT was scored using Common Terminology Criteria for Adverse Events, version 4. Receiver-operating characteristic curves were used to identify patient and dosimetric factors associated with CWT and to determine optimal dose-volume histogram parameters/cutoffs. Cox regression univariate analysis was used to associate factors to time-dependent onset of CWT. RESULTS: Thirty-nine liver lesions were treated with a median dose of 60 GyE (range, 35-67.5) in 15 fractions (range, 13-20). Median follow-up was 11 months (range, 2-44). Grade ≥2 and 3 CW pain occurred in 7 (19%) and 4 (11%) patients, respectively. Median time to onset of pain was 6 months (range, 1-14). No patients had radiographic rib fracture. On univariate analysis, CW equivalent 2 Gy dose with an α/ß = 3 Gy (EQD2α/ß=3), V57 >20 cm3 (hazard ratio [HR], 2.7; P = .004), V63 >17 cm3 (HR, 2.7; P = .003), and V78 >8 cm3 (HR, 2.6; P = .003) had the strongest association with grade ≥2 CW pain, as did tumor dose of >75 Gy EQD2α/ß=10 (HR, 8.7; P = .03). No other patient factors were associated with CWT. CONCLUSIONS: CWT after hypofractionated PBT for liver malignancies is clinically relevant. For a 15-fraction regimen, V47 >20 cm3, V50 >17 cm3, and V58 >8 cm3 were associated with higher rates of CWT. Further investigation of PBT techniques to reduce CW dose are warranted.

D cyclins in CD5+ B-cell lymphoproliferative disorders: cyclin D1 and cyclin D2 identify diagnostic groups and cyclin D1 correlates with ZAP-70 expression in chronic lymphocytic leukemia.

We analyzed protein expression of cyclin D1, cyclin D2, and cyclin D3 using high-resolution enzymatic amplification staining and flow cytometry in the neoplastic cells from 80 patients with CD5+ B-cell lymphoproliferative disorders. The D cyclins were expressed differentially in chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), and mantle cell lymphoma (MCL) with strong staining of cyclin D1 and D2 in MCL, strong staining of cyclin D1 but weak staining of cyclin D2 in 4 of 5 PLLs, and low-level staining for both cyclins in most CLLs. No correlation between cyclin D1 and D2 and growth rates or CD38 expression was observed. However, cyclin D1 levels were significantly higher in ZAP-70+ CLL cases, although no association between ZAP-70 and cyclin D2 was detected. The results indicate that flow cytometric analysis of D cyclins may help in classification of CD5+ B-cell lymphoproliferative disorders.

Anatomical contouring variability in thoracic organs at risk.

The purpose of this study was to determine whether contouring thoracic organs at risk was consistent among medical dosimetrists and to identify how trends in dosimetrist׳s education and experience affected contouring accuracy. Qualitative and quantitative methods were used to contextualize the raw data that were obtained. A total of 3 different computed tomography (CT) data sets were provided to medical dosimetrists (N = 13) across 5 different institutions. The medical dosimetrists were directed to contour the lungs, heart, spinal cord, and esophagus. The medical dosimetrists were instructed to contour in line with their institutional standards and were allowed to use any contouring tool or technique that they would traditionally use. The contours from each medical dosimetrist were evaluated against "gold standard" contours drawn and validated by 2 radiation oncology physicians. The dosimetrist-derived contours were evaluated against the gold standard using both a Dice coefficient method and a penalty-based metric scoring system. A short survey was also completed by each medical dosimetrist to evaluate their individual contouring experience. There was no significant variation in the contouring consistency of the lungs and spinal cord. Intradosimetrist contouring was consistent for those who contoured the esophagus and heart correctly; however, medical dosimetrists with a poor metric score showed erratic and inconsistent methods of contouring.

D cyclins in lymphocytes.

BACKGROUND: D cyclins are essential for the progression of cells through the G1 phase of the cell cycle. There are three distinct D cyclins. Cyclin D1 has been shown to be expressed by many different types of cells but not by lymphocytes. Cyclins D2 and D3 have been found in lymphocytes. METHODS: We used high-resolution enzymatic amplification staining technology in conjunction with flow cytometry and confocal microscopy and with immunoblotting to reassess the expression of the D cyclins in human lymphocytes. RESULTS: Using high-resolution technology for flow cytometry, we found all three D cyclins in quiescent human peripheral blood lymphocytes. Cyclin D1 was expressed in quiescent and activated cells at levels commensurate with those of actively proliferating tumor cell lines. Cyclin D1 was functional inasmuch as it was complexed with CDK4. In the quiescent cells, cyclin D1 was expressed in the cytoplasm but, after activation, was found in the nucleus. CONCLUSIONS: These findings demonstrate that lymphocytes express cyclin D1 and necessitate a reappraisal of the hypothesis that the D cyclins subsume redundant activities with tissue-specific expression.