Urinary Insulin-Like Growth Factor-Binding Protein 7 (IGFBp7), Urinary Tissue Inhibitor of Matrix Metalloproteinase 2 (TIMP2), and Serum Transgelin as Novel Biomarkers of Kidney Injury in Multiple Myeloma.

Renal dysfunction is a common complication of MM and is associated with poor prognosis, particularly when progressive. Early identification of renal dysfunction is essential for prompt treatment for disease control and restoration of renal function. Urinary insulin-like growth factor-binding protein 7 (IGFBP-7), urinary tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and serum transgelin levels were measured using enzyme-linked immunosorbent assays and evaluated as biomarkers for the prediction of renal impairment in patients with multiple myeloma. U IGFBP-7/creatinine ratio, U TIMP2/creatinine ratio, and serum transgelin levels were higher in patients with MM than healthy controls, and predicted renal insufficiency in MM. Serum transgelin, urinary IGFBp7, and TIMP2 levels may have utility as biomarkers of renal tubular injury and predict future renal impairment in patients with MM.

Trichinella spiralis Larval Extract as a Biological Anti-Tumor Therapy in a Murine Model of Ehrlich Solid Carcinoma.

Trichinella spiralis (T. spiralis) is an immunomodulating parasite that can adversely affect tumor growth and extend host lifespan. The aim of this study was to elucidate the mechanisms by which T. spiralis larval antigens achieve this effect using Ehrlich solid carcinoma (ESC) murine model. Assessment was done by histopathological and immunohistochemical analysis of caspase-3, TNF-α, Ki-67 and CD31. Additionally, Bcl2 and Bcl2-associated protein X (Bax) relative gene expression was assessed by molecular analysis for studying the effect of T. spiralis crude larval extract (CLE) antigen on tumor necrosis, apoptosis, cell proliferation and angiogenesis. We found that both T. spiralis infection and CLE caused a decrease in the areas of necrosis in ESC. Moreover, they led to increased apoptosis through activation of caspase-3, up-regulation of pro-apoptotic gene, Bax and down-regulation of anti-apoptotic gene, Bcl2. Also, T. spiralis infection and CLE diminished ESC proliferation, as evidenced by decreasing Ki-67. T. spiralis infection and CLE were able to suppress the development of ESC by inhibiting tumor proliferation, inducing apoptosis and decreasing tumor necrosis, with subsequent decrease in tumor metastasis. T. spiralis CLE antigen may be considered as a promising complementary immunotherapeutic agent in the treatment of cancer.

Salvage Whole-Pelvic Radiation and Long-Term Androgen-Deprivation Therapy in the Management of High-Risk Prostate Cancer: Long-Term Update of the McGill 0913 Study.

PURPOSE: To report the long-term outcomes of the McGill 0913 study and the potential benefits of combining prostate-bed radiotherapy (PBRT), pelvic-lymph-node radiotherapy (PLNRT), and long term ADT (LT-ADT). MATERIALS AND METHODS: From 2010 to 2016, 46 high-risk prostate cancer patients who experienced biochemical recurrence (BCR) after radical prostatectomy (RP) were enrolled in this single-arm phase II clinical trial. The patients were eligible if they had a Gleason score > 8, locally advanced disease (≥pT3), a preoperative PSA of >20 ng/mL, or positive lymph nodes (LN). The patients were treated with a combination of 24 months of ADT, PBRT, and PLNRT. The primary outcome was biochemical progression-free survival (bPFS) and the predefined secondary endpoints included distant-metastasis-free survival (DMFS), overall survival (OS), and toxicity. In this update, we also report the median follow-up of 8.8 years and 10 years OS. RESULTS: At a median follow-up of 8.8 years, 43 patients were eligible for analysis. The median pre-salvage PSA was 0.30 µg/L. Half (51%) of the patients (n = 22) had positive margins, 40% (n = 17) had Gleason scores > 8, 63% (n = 27) had extracapsular extension, 42% (n = 18) had seminal vesicle invasion, and 19% (n = 8) had LN involvement. The 10-year bPFS was 68.3 %. The 10-year DMFS was 72.9%. The 10-year OS was 97%. There were two non-cancer-related deaths. The first patient died of congestive heart failure while the other died of an unknown cause. No new toxicity was observed after the initial report. CONCLUSIONS: Our study demonstrates that treatment escalation with PBRT, PLNRT, and LT-ADT improves long term outcomes. In view of the recently published SPPORT study, we conclude that this novel approach of treatment intensification in high-risk post-prostatectomy patients is safe and effective, and that it should be offered as the standard of care.

Salvage external beam radiotherapy after HIFU failure in localized prostate cancer: A single institution experience.

Purpose/objectives: High-intensity focused ultrasound (HIFU) remains investigational as primary treatment for localized prostate cancer but is sometimes offered to select patients. At HIFU failure, data guiding salvage treatment is limited to small retrospective series with short follow-up. We evaluated our institutional experience using salvage radiation therapy (SRT) after HIFU failure. Materials/methods: We conducted a retrospective analysis of patients with local failure post-HIFU who received salvage image-guided external beam radiation therapy (EBRT) delivered via intensity-modulated radiotherapy (IMRT). Our primary endpoint was biochemical failure-free survival (bFFS) defined as prostate-specific antigen (PSA) nadir + 2 ng/mL. Secondary endpoints included metastasis-free survival (MFS) and overall survival (OS). Endpoints were evaluated using Kaplan-Meier analysis. Results: From 2013 to 2018, 12 out of 96 patients treated with primary HIFU received SRT via conventional or moderate hypofractionation. Median time from HIFU to SRT was 13.5 months. Seven patients had stage migration to high-risk disease at the time of SRT. Mean PSA prior to SRT was 8.2ug/L and mean nadir post-SRT was 1.2ug/L. Acute International Prostate Symptom Score (IPSS) as well as International Index of Erectile Dysfunction (IIEF) scores were similar to baseline (p = 0.5 and 0.1, respectively). Late toxicities were comparable to those reported after primary EBRT for localized prostate cancer. At a median follow-up of 46 months, the OS was 100%. The 5-year bFFS and MFS were both 83.3%. Conclusions: To our knowledge, we report one of the largest series on contemporary SRT post HIFU failure. We show that SRT is feasible, effective and carries no additional acute or delayed toxicity.

Does Interfraction Cone Beam Computed Tomography Improve Target Localization in Prostate Bed Radiotherapy?

PURPOSE: In this prospective phase II study, we investigated whether cone beam computed tomography scan was a superior method of image-guided radiotherapy relative to 2D orthogonal kilovoltage images in the post-radical prostatectomy setting. METHODS: A total of 419 treatment fractions were included in this analysis. The shifts required to align the patient for each treatment were performed using 3D matching between cone beam computed tomography scans and the corresponding computed tomography images used for planning. This was compared with the shifts obtained from 2D orthogonal kilovoltage images, matching with the corresponding digitally reconstructed radiographs. Patients did not have fiducials inserted to assist with localization. Interfractional changes in the bladder and rectal volumes were subsequently measured on the cone beam computed tomography images for each fraction and compared to the shift differences between orthogonal kilovoltage and cone beam computed tomography scans. The proportion of treatment fractions with a shift difference exceeding the planning target volume of 7 mm, between orthogonal kilovoltage and cone beam computed tomography scans, was calculated. RESULTS: The mean vertical, lateral, and longitudinal shifts resulted from 2D match between orthogonal kilovoltage images and corresponding digitally reconstructed radiographs were 0.353 cm (interquartile range: 0.1-0.5), 0.346 cm (interquartile range: 0.1-0.5), and 0.289 cm (interquartile range: 0.1-0.4), compared to 0.388 cm (interquartile range: 0.1-0.5), 0.342 cm (interquartile range: 0.1-0.5), and 0.291 cm (interquartile range: 0.1-0.4) obtained from 3D match between cone beam computed tomography and planning computed tomography scan, respectively. Our results show a significant difference between the kilovoltage and cone beam computed tomography shifts in the anterior-posterior direction ( P = .01). The proportion of treatment fractions in which the differences in kilovoltage and cone beam computed tomography shifts between exceeded the 7 mm planning target volume margin was 6%, 2%, and 3% in the anterior-posterior, lateral, and superior-inferior directions, respectively. CONCLUSION: We prospectively demonstrated that the daily use of volumetric cone beam computed tomography for treatment localization in post-radical prostatectomy patients demonstrated an increased need for a shift in patient position. This suggests that in post-radical prostatectomy patients the daily cone beam computed tomography imaging improved localization of the prostate bed and may have prevented a limited number of geographic misses, compared to daily kilovoltage imaging that was not assisted with fiducials.

What Is the Optimal Radiation Technique for Esophageal Cancer? A Dosimetric Comparison of Four Techniques.

Background Esophageal cancer treatment requires large radiation fields due to the deep location of the esophagus in the mediastinum and the high incidence of radial spread. There is no optimal radiation technique to ensure appropriate target coverage and minimal dose to all normal structures. Methods Fifteen consecutive cases of locally advanced esophageal cancer treated with radical chemoradiation (CRT) were analyzed. The total prescribed dose was 50.4 Gy in 28 fractions. A total of 60 plans were generated for analysis, including four different methods for each case. Method 1 consisted of a four-field conformal technique; method 2 was a two-plan technique (antero-posterior (AP), postero-anterior (PA), two posterior oblique fields (RPO and LPO)); method 3 was a three-field conformal technique (AP, LPO, RPO); and method 4 was a volumetric modulated arc radiotherapy (VMAT) technique. Dose ratios were calculated using the minimum, maximum, mean, and median doses of methods 2-4 over the dose of method 1. Ratios for the planning target volume (PTV) and to surrounding organs were analyzed. Results The mean PTV dose ratio ranged from 0.994 to 1.048 (SD = 0.01) representing an adequate target coverage for all techniques based on an analysis of variance (ANOVA). For the lungs, method 2 had the lowest lung V20 with a ratio of 0.861 (SD = 0.12), whereas method 3 had the highest with 1.644 (SD = 0.14). For the heart, method 3 had the lowest heart V40 with a mean dose ratio of 0.807 (SD = 0.09), whereas method 2 had the highest with 1.160 (SD = 0.11). For the liver, method 2 had the lowest V30 with a mean ratio of 0.857 (SD = 0.1) whereas method 4 had the highest with 1.672 (SD = 0.48). For the spinal cord, method 3 had the lowest mean dose ratio of 0.559 (SD = 0.09) whereas method 2 had the highest with 1.094 (SD = 0.04). Conclusion The four radiation techniques for esophageal cancer treatment were appropriate for target coverage. Method 2 had the most organ-sparing effect for the lungs and liver, and method 3 for the heart and spinal cord. VMAT did not add any significant sparing. A case-by-case decision should be made based on the patient's comorbidities.

Local ablative stereotactic body radiotherapy for oligometastatic prostate cancer.

PURPOSE OF REVIEW: The oligometastases is considered an intermediate state of the disease between localized and wide spread metastases. Local ablative therapy to oligometastatic prostate cancer is gaining significant traction and stereotactic body radiotherapy (SBRT) is an emerging treatment modality for this patient population. In this review, we report our literature review of SBRT to prostate oligometastases. Current evidence on the role of SBRT in oligometastatic prostate cancer reported in the last 10 years was summarized. Criteria for inclusion included studies with prostate cancer only as the primary site. RECENT FINDINGS: The unique properties of the oligometastatic prostate cancer appear to carry a better prognosis than wide spread metastatic disease, especially if these metastases are amenable to local ablative therapies. Our literature review revealed that local ablative therapy, using SBRT to prostate oligometastases, is associated with significant 2-years local control and acceptable toxicity profile. SUMMARY: SBRT to oligometastatic prostate cancer patients is feasible and carries an acceptable toxicity profile. The randomized phase II and III trials, currently underway, should clearly define the real benefit of this approach on progression-free and overall survival outcomes.