Purpose: Our purpose was to compare toxicity and biochemical control in postprostatectomy patients treated with conventional (66 Gy) or dose-intensified (72 Gy) radiation therapy. Methods and Materials: Patients who had stage pT3-4, positive surgical margins, or rising prostate-specific antigen 0.2 ng/mL after radical prostatectomy were randomly assigned to receive either 66 Gy in 33 fractions or 72 Gy in 36 fractions. A primary endpoint was to assess the difference in biochemical progression-free survival (bPFS) between these 2 cohorts, and secondary endpoints were to assess differences in genitourinary (GU), gastrointestinal (GI), and hematologic toxicities between these 2 cohorts. bPFS was estimated by the KaplaneMeier method and toxicities were compared using the c 2 test.Results: Between September 2011 and November 2016, 144 patients were enrolled: 71 patients to the 66 Gy cohort and 73 patients to the 72 Gy cohort. The median follow-up time was 48.5 months (range, 14-79 months). There was no difference in 4-year bPFS between the 66 Gy and 72 Gy cohorts (75.9% vs 82.6%; P Z .299). However, in patients with a higher Gleason score (8-10), the 72 Gy cohort had statistically significant improvement in bPFS compared with the 66 Gy cohort (79.7% vs 55.7%; P Z .049). Toxicity analysis showed no difference in 2 acute or late GI or GU toxicities between these 2 cohorts. A total of 48 patients were scored as urinary incontinence before radiation therapy, of which 39 (81.3%) reported incontinence recovery or stable at 1-year follow-up, and only 9 (18.8%) patients reported worsening. There was no difference between the 2 cohorts in urinary incontinence either at baseline or at 1-year follow-up.Conclusions: Dose escalation (72 Gy) demonstrated no improvement in 4-year bPFS compared with the 66 Gy regimen. However, the dose escalation was not associated with greater acute or late GU or GI toxicities and did not increase urinary incontinence. Ó 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Volume 106 Number 2 2020Postoperative RT for prostate cancer 283Abbreviations: ART Z adjuvant radiation therapy; ISUP Z International Society of Urologic Pathology; PSA Z prostate-specific antigen; PUFH Z Peking University First Hospital; RP Z radical prostatectomy; RT Z radiation therapy; SRT Z salvage radiation therapy; WPRT Z whole pelvic radiation therapy. Note: P values were calculated by Mann-Whitney U test or c 2 test where appropriate.
Platelet to lymphocyte ratio (PLR) is a parameter reflecting inflammatory responses in patients with cancer. Several studies have investigated the prognostic value of PLR in patients with colorectal cancer (CRC); however, the results are controversial. Thus, we carried out a meta-analysis to evaluate the association between PLR and CRC prognostication. Relevant articles were retrieved through PubMed, Embase, and Web of Science, and pooled hazard ratio (HR) and 95% confidence interval (CI) were computed by using STATA V.12.0. Both the random-effects model and fixed-effects model were utilized. A total of 13 studies (14 cohorts) with 8,601 patients were included in the meta-analysis. Pooled HRs and 95% CIs demonstrated that increased PLR predicted poor overall survival (OS) (HR = 1.81, 95%CI:1.42–2.31, p<0.001; I2 = 65%, Ph = 0.002), disease-free survival (DFS) (HR = 1.84, 95%CI:1.22–2.76, p = 0.003; I2 = 78.3%, Ph<0.001) and recurrence-free survival (RFS) (HR = 1.84, 95%CI:1.41–2.41, p<0.001; I2 = 0, Ph = 0.686), although this was not the case for cancer-specific survival (CSS) (HR = 1.75, 95%CI:0.59–5.17, p = 0.309; I2 = 66.2%, Ph = 0.085) or time to recurrence (TTR) (HR = 1.21 95%CI:0.62–2.36, p = 0.573;I2 = 58.4%, Ph = 0.121). Subgroup analysis showed that PLR enhanced the prognostic value for OS in Caucasian patients, in small sample studies and for metastatic disease; however, this was not the case with rectal cancer. Furthermore, elevated PLR predicted reduced DFS in Caucasians and not in Asians. In conclusion, our meta-analysis showed that high PLR was a significant biomarker for poor OS, DFS, and RFS in patients with CRC; however, it had no association with CSS or TTR.
ObjectiveThis study was aimed to compare survival outcomes in high-risk prostate cancer (PCa) patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP).Materials and methodsThe Surveillance, Epidemiology, and End Results (SEER) database was used to identify PCa patients with high-risk features who received RP alone or EBRT alone from 2004 to 2008. Propensity-score matching (PSM) was performed. Kaplan–Meier survival analysis was used to compare cancer-specific survival (CSS) and overall survival (OS). Multivariate Cox regression analysis was used to identify independent prognostic factors.ResultsA total of 24,293 patients were identified, 14,460 patients receiving RP and 9833 patients receiving EBRT. Through PSM, 3828 patients were identified in each group. The mean CSS was 128.6 and 126.7 months for RP and EBRT groups, respectively (P<0.001). The subgroup analyses showed that CSS of the RP group was better than that of the EBRT group for patients aged <65 years (P<0.001), White race (P<0.001), and married status (P<0.001). However, there was no significant difference in CSS for patients aged ≥65 years, Black race, other race, and unmarried status. Similar trends were observed for OS. Multivariate analysis showed that EBRT treatment modality, T3–T4 stage, Gleason score 8–10, and prostate-specific antigen >20 ng/mL were significant risk factors for both CSS and OS.ConclusionThis study suggested that survival outcomes might be better with RP than EBRT in high-risk PCa patients aged <65 years; however, RP and EBRT provided equivalent survival outcomes in older patients, which argues for primary radiotherapy in this older cohort.
Compelling evidence indicates that radiotherapy (RT) has a systemic inhibitory effect on nonirradiated lesions (abscopal effect) in addition to the ablation of irradiated tumors. However, this effect occurs only in rare circumstances in clinical practice, and mechanisms underlying the abscopal effect of RT are neither fully understood nor therapeutically utilized. Here we identified that intercellular adhesion molecule-1 (ICAM-1), an inducible glycoprotein of the immunoglobulin superfamily, is up-regulated in nonirradiated tumors responsive to RT. ICAM-1 expression in preclinical animal models can be noninvasively detected by optical imaging and positron emission tomography (PET) using near-infrared fluorescence dye- and 64Cu-labeled imaging probes that we synthesized, respectively. Importantly, the expression levels of ICAM-1 determined by quantitative PET imaging showed a strong negative linear correlation with the growth of nonirradiated tumors. Moreover, genetic or pharmacologic up-regulation of ICAM-1 expression by either an intratumoral injection of engineered recombinant adenovirus or systemic administration of a Toll-like receptor 7 agonist-capsulated nanodrug could induce markedly increased abscopal responses to local RT in animal models. Mechanistic investigation revealed that ICAM-1 expression can enhance both the activation and tumor infiltration of CD8+ T cells to improve the responses of the nonirradiated tumors to RT. Together, our findings suggest that noninvasive PET imaging of ICAM-1 expression could be a powerful means to predict the responses of nonirradiated tumors to RT, which could facilitate the exploration of new combination RT strategies for effective ablation of primary and disseminated lesions.
PurposeBulky non-small cell lung cancer (NSCLC) is difficult to achieve effective local control by conventionally fractionated radiotherapy (CRT). The present work aims to evaluate the safety and efficacy of partial stereotactic ablative boost radiotherapy (P-SABR) in bulky NSCLC.Patients and methodsFrom December 2012 through August 2017, 30 patients with bulky NSCLC treated with P-SABR technique were analyzed. The P-SABR plan consisted of one partial SABR plan (5–9 Gy/f, 3–6 fractions) to gross tumor boost (GTVb), followed by one CRT plan to the planning target volume (PTV). GTVb was the max volume receiving SABR to guarantee the dose of organs-at-risks (OARs) falloff to about 3 Gy/f. The total dose of PTV margin was planned to above 60 Gy. The simply CRT plans were created using the same planning parameters as the original plan, with the goal to achieve comparable OARs doses and PTV margin dose to the P-SABR plan. Dosimetric variables were acquired in both P-SABR and compared CRT plans. Toxicity, local control, and survival were also evaluated.ResultsMedian follow-up in survivors was 10.3 months (range=2.3–39.4 months). Eleven patients (36.7%) had partial response (PR) and ten patients (33.3%) had stable disease (SD). Two-year overall survival was 55.6%. Two-year local control rate was 85.7%. No severe acute side effects >CTCAE Grade III were observed. Compared to the simply CRT plan, P-SABR plans achieved similar doses to the OARs and Dmin, but increased dose at the isocenter, Dmean, Dmax, and biological equivalent dose (BED) significantly (P<0.05). BED in the tumor center could reach 107.3 Gy (93.2–132 Gy). Patients with B90≥65% achieved a higher local control rate than those with B90<65% (P=0.010).ConclusionThis retrospective study suggests that P-SABR is feasible and well tolerated in bulky NSCLC. Local control rate is encouraging, especially for the B90≥65% group, which may due to the ability of P-SABR to optimize BED with equivalent toxicity.
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