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PURPOSE: Head and neck cancers radiotherapy (RT) is associated with inevitable injury to parotid glands and subsequent xerostomia. We investigated the utility of SUV derived from 18FDG-PET to develop metabolic imaging biomarkers (MIBs) of RT-related parotid injury. METHODS: Data for oropharyngeal cancer (OPC) patients treated with RT at our institution between 2005 and 2015 with available planning computed tomography (CT), dose grid, pre- & first post-RT 18FDG-PET-CT scans, and physician-reported xerostomia assessment at 3-6 months post-RT (Xero 3-6 ms) per CTCAE, was retrieved, following an IRB approval. A CT-CT deformable image co-registration followed by voxel-by-voxel resampling of pre & post-RT 18FDG activity and dose grid were performed. Ipsilateral (Ipsi) and contralateral (contra) parotid glands were sub-segmented based on the received dose in 5 Gy increments, i.e. 0-5 Gy, 5-10 Gy sub-volumes, etc. Median and dose-weighted SUV were extracted from whole parotid volumes and sub-volumes on pre- & post-RT PET scans, using in-house code that runs on MATLAB. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test differences pre- and post-RT. RESULTS: 432 parotid glands, belonging to 108 OPC patients treated with RT, were sub-segmented & analyzed. Xero 3-6 ms was reported as: non-severe (78.7%) and severe (21.3%). SUV- median values were significantly reduced post-RT, irrespective of laterality (p = 0.02). A similar pattern was observed in parotid sub-volumes, especially ipsi parotid gland sub-volumes receiving doses 10-50 Gy (p < 0.05). Kruskal-Wallis test showed a significantly higher mean RT dose in the contra parotid in the patients with more severe Xero 3-6mo (p = 0.03). Multiple logistic regression showed a combined clinical-dosimetric-metabolic imaging model could predict the severity of Xero 3-6mo; AUC = 0.78 (95%CI: 0.66-0.85; p < 0.0001). CONCLUSION: We sought to quantify pre- and post-RT 18FDG-PET metrics of parotid glands in patients with OPC. Temporal dynamics of PET-derived metrics can potentially serve as MIBs of RT-related xerostomia in concert with clinical and dosimetric variables.
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BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with ill-defined therapeutic targets. Androgen receptor (AR) and tumour-infiltrating lymphocytes (TILs) had a prognostic and predictive value in TNBC. The relationship between AR, TILs and clinical behaviour is still not fully understood. METHODS: Thirty-six TNBC patients were evaluated for AR (positive if ≥1% expression), CD3, CD4, CD8 and CD20 by immunohistochemistry. Stromal TILs were quantified following TILs Working Group recommendations. Lymphocyte-predominant breast cancer (LPBC) was defined as stromal TILs ≥ 50%, whereas lymphocyte-deficient breast cancer (LDBC) was defined as <50%. RESULTS: The mean age was 52.5 years and 27.8% were ≥60 years. Seven patients (21.2%) were AR+. All AR+ cases were postmenopausal (≥50 years old). LPBC was 32.2% of the whole cohort. Median TILs were 37.5% and 10% (p = 0.1) and median CD20 was 20% and 7.5% (p = 0.008) in AR- and AR+, respectively. Mean CD3 was 80.7% and 93.3% (p = 0.007) and CD8 was 75% and 80.8% (p= 0.41) in AR- and AR+, respectively. All patients who were ≥60 years old expressed CD20. LDBC was found to be significantly higher in N+ versus N- patients (p = 0.03) with median TILs of 20% versus 50% in N+ versus N-, respectively (p = 0.03). LDBC was associated with higher risk of lymph node (LN) involvement (odds ratio = 6; 95% CI = 1.05-34.21; p = 0.04). CONCLUSIONS: AR expression was evident in older age (≥50 years). Median CD20 was higher in AR- TNBC, while mean CD3 was higher in AR+ tumours. LDBC was associated with higher risk of LN involvement. Larger studies are needed to focus on the clinical impact of the relation between AR and TILs in TNBC.
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AIM: A single-institution, retrospective study was performed to investigate potential techniques to minimize radiation exposure to the testicles during heterotopic ossification (HO) prophylaxis. We report the impact of split-beam technique (SBT) and different photon energies on the total dose of radiation received by the testicles during prophylaxis of HO. MATERIALS AND METHODS: Between 2008 and 2010, we identified 64 patients with traumatic acetabular fractures who underwent surgery followed by radiation therapy (RT) without testicular shielding. Postoperative RT was delivered within 72 h in a single fraction of 700 cGy using 6-18 MV photons, without testicular shielding due to patient refusal. All patients underwent 3-D RT planning in which the testicles were contoured as a region of interest and dose-volume histograms (DVH) were generated. Additional treatment planning trials were created for each patient by utilizing a SBT medially and by using different photon energies (6, 10 and 18 MV) to study the effects of these maneuvers on the delivered dose to the testicles. RESULTS: In reviewing the DVH, it was noted that the mean dose delivered to the testicles was 10 cGy (range=3-40). The maximum dose was 31 cGy (range=7-430). When SBT was utilized, a significant reduction in the mean (44%) and maximum (47%) doses delivered to the testicles was noted. Further reductions in the mean (26%) and maximum (14%) doses were achieved by using higher-energy (10-18 MV) beams. The radiation doses to the testicles from the CT simulation and the two portal images were estimated to be 4 and 1.5 cGy, respectively. CONCLUSION: Low-dose prophylactic RT to prevent HO around the hip causes a low, but likely biologically meaningful, radiation dose to be delivered to the testicles. This dose could be further reduced by using a medial SBT and photon energies above 6 MV. Testicular shielding should be offered to all male patients receiving such RT. In addition, all patients should be informed about the consequences of testicular radiation as part of their informed consent.