Radical treatment of localized prostate cancer in elderly patients may lead to unacceptable treatment-associated toxicities that adversely impact quality of life without improving survival outcomes. ...This study reports on a cohort of 54 elderly (>70 years) patients that received 4000–5000 cGy of palliative external beam radiotherapy (EBRT) as an alternative to androgen deprivation therapy (ADT). The primary outcome of interest was the period of ADT-free survival, and secondary outcomes included overall survival (OS) and metastases-free survival (MFS). Kaplan–Meier regression was used to estimate survival outcomes. Thirty-six (67%) patients achieved a break in ADT post-radiotherapy, with a median time to ADT reinitiation of 20 months. Common Terminology Criteria for Adverse Events (CTCAE) were limited to low-grade gastrointestinal (GI) or genitourinary (GU) toxicities, with no skin toxicities observed. Grade 1 GI toxicity was observed in 9 (17%) patients, and grades 1 and 2 GU toxicities were observed in 13 (24%) and 3 (6%) patients, respectively, with no higher-grade toxicities reported. Five-year MFS and OS were 56% and 78%, respectively. In summary, the treatment regimen was well-tolerated and achieved durable ADT-free survival in most patients. Dose-reduced EBRT appears to be a viable alternative to ADT in elderly patients with localized prostate cancer.
•Resource constraints have led to prolonged wait-times for prostate brachytherapy.•Increased wait times predict a significant increase in recurrence and metastases.•Better resource planning is needed ...to reduce management delays & improve outcomes.
It has previously been shown that increased wait times for prostatectomy are associated with poorer outcomes in intermediate-risk prostatic carcinoma (PCa). However, the impact of wait times on PCa outcomes following low-dose-rate brachytherapy (LDR-BT) are unknown.
We retrospectively reviewed 466 intermediate-risk PCa patients that underwent LDR-BT at a single comprehensive cancer center between 2003 and 2016. Wait times were defined as the time from biopsy to LDR-BT. The association of wait times with outcomes was evaluated using Cox and Fine-Gray regression in both univariate and multivariate models.
Median (interquartile range) follow-up and wait time for all patients were 8.1 (6.3–10.4) years and 5.1 (3.9–6.9) months, respectively. Among NCCN unfavourable intermediate-risk (UIR) patients (n = 170; 36%), increased wait times predicted both a greater cumulative incidence of recurrence MHR = 1.01/month of wait time (95% CI: 1.00–1.03); P = 0.044 and metastases MHR = 1.04/month of wait time (95% CI: 1.02–1.06); P < 0.001 in multivariate modeling. In NCCN favourable intermediate-risk (FIR) patients, there was no significant association between wait time and recurrence or metastases risk. Among all intermediate-risk patients, wait time was associated with an increase in the incidence of metastases MHR = 1.03/month of wait time (95% CI: 1.02–1.05); P < 0.001, but not recurrence in multivariate models. There was no association between wait time and overall survival in the UIR, FIR, or all intermediate-risk cohorts.
Resource constraints within this center’s public healthcare system have contributed to waitlists exceeding 5-months in length. This study finds that patients with UIR PCa experience a 1% increase in the risk of recurrence and 4% increase in the risk of metastases with each additional month of delay in definitive disease management. Preventing such extended management delays in LDR-BT may improve disease-related outcomes in patients with PCa.
To develop a model for prostate specific antigen (PSA) values at one year among patients treated with intraoperatively planned
I prostate brachytherapy (IOPB).
Four hundred and deven patients treated ...with IOPB for prostate adenocarcinoma were divided into four groups: those with PSA values ≥ 3 ng/ml; < 3 and ≥ 2; < 2 and ≥ 1 or PSA < 1 between 10.5 and 14.5 months post implantation (1yPSA). Ordinal regression analysis was then performed between patient, tumor, and treatment characteristics. 1yPSA values were also compared with toxicity outcomes.
Median 1yPSA was 0.77 (0.04-17.36). Thirty-two patients (8%) had a PSA ≥ 3; 35 (9%) had PSA < 3, ≥ 2; 87 (21%) had PSA < 2, ≥ 1, and most patients 254 (62%) had PSA < 1. PSA response was independent of gland volume, Gleason score, clinical stage, seed activity, V
, V
, D
, or number of needles and seeds used. Older patients had significantly lower 1yPSA; median ages 65.1 (46.5-81.0), 62.1 (50.4-79.5), 60.5 (47.1-80.3), and 58.1 (45.1-74.2) years for each of the 1yPSA groups respectively (
< 0.001). Also, both implant V
(
< 0.001) and initial PSA values (
= 0.04) were predictive of 1yPSA values. There was no correlation between 1yPSA values and toxicity encountered.
PSA response at 1 year post IOPB appears to be dependent on patient age, initial PSA, and implant V
. Our results provide reassurance that parameters other than biochemical failure influence 1yPSA values.
To determine if principal component analysis (PCA) and standard parameters of rectal and bladder wall dose-volume histograms (DVHs) of prostate cancer patients treated with hypofractionated ...image-guided intensity-modulated radiotherapy (hypo-IMRT) can predict acute and late gastrointestinal (GI) toxicity.
One hundred twenty-one patients underwent hypo-IMRT at 3 Gy/fraction, 5 days/week to either 60 Gy or 66 Gy, with daily online image guidance. Acute and late GI and genitourinary (GU) toxicity were recorded weekly during treatment and at each follow-up. All Radiation Therapy Oncology Group (RTOG) criteria toxicity scores were dichotomized as <2 and ≥2. Standard dosimetric parameters and the first five to six principal components (PCs) of bladder and rectal wall DVHs were tested for association with the dichotomized toxicity outcomes, using logistic regression.
Median follow-up of all patients was 47 months (60 Gy cohort = 52 months; 66 Gy cohort = 31 months). The incidence rates of ≥2 acute GI and GU toxicity were 14% and 29%, respectively, with no Grade ≥3 acute GU toxicity. Late GI and GU toxicity scores ≥2 were 16% and 15%, respectively. There was a significant difference in late GI toxicity ≥2 when comparing the 66 Gy to the 60 Gy cohort (38% vs. 8%, respectively, p = 0.0003). The first PC of the rectal DVH was associated with late GI toxicity (odds ratio OR, 6.91; p < 0.001), though it was not significantly stronger than standard DVH parameters such as Dmax (OR, 6.9; p < 0.001) or percentage of the organ receiving a 50% dose (V50) (OR, 5.95; p = 0 .001).
Hypofractionated treatment with 60 Gy in 3 Gy fractions is well tolerated. There is a steep dose response curve between 60 Gy and 66 Gy for RTOG Grade ≥2 GI effects with the dose constraints employed. Although PCA can predict late GI toxicity for patients treated with hypo-IMRT for prostate cancer, it provides no additional information over using more standard DVH parameters.
Abstract Purpose To estimate the late morbidity of a novel, hypofractionated external beam radiotherapy schedule of 55 Gy in 16 fractions (4 fractions/week, 3.4 Gy per fraction) for localized ...prostate cancer. Methods and materials A multi-center phase 2 study enrolled seventy-three patients between September 2004 and June 2006. After insertion of fiducial gold markers, they were treated with image-guidance (IGRT) using conformal techniques with intensity-modulation, if necessary, and then followed every 6 months for toxicity rating and PSA. Patient reported outcomes were collected yearly. Median follow up was 4.6 years. Results At 4 years post-radiotherapy, the cumulative incidence of combined urinary and bowel grade 3 toxicity was 7% (95% CI 3–16%) and grade 2+ was 33% (95% CI 24–46%). All except two patients recovered from their grade 3 events. Patient-reported reduction of function was most pronounced at year two for urinary function (mean −7, SD 16), and at year one for bowel function (mean −7, SD 21). The cumulative incidence of biochemical (PSA nadir + 2) or biopsy-proven relapse at 4 years was 9% (95% CI 4–18%). Conclusions Hypofractionated radiotherapy is clinically feasible and more convenient than conventional schedules for patients with localized prostate cancer. Phase 3 multicenter studies are on-going ( NCT00126165 ).
To examine the trafficking, assembly, and turnover of connexin43 (Cx43) in living cells, we used an enhanced red-shifted mutant of green fluorescent protein (GFP) to construct a Cx43-GFP chimera. ...When cDNA encoding Cx43-GFP was transfected into communication-competent normal rat kidney cells, Cx43-negative Madin-Darby canine kidney (MDCK) cells, or communication-deficient Neuro2A or HeLa cells, the fusion protein of predicted length was expressed, transported, and assembled into gap junctions that exhibited the classical pentalaminar profile. Dye transfer studies showed that Cx43-GFP formed functional gap junction channels when transfected into otherwise communication-deficient HeLa or Neuro2A cells. Live imaging of Cx43-GFP in MDCK cells revealed that many gap junction plaques remained relatively immobile, whereas others coalesced laterally within the plasma membrane. Time-lapse imaging of live MDCK cells also revealed that Cx43-GFP was transported via highly mobile transport intermediates that could be divided into two size classes of <0.5 microm and 0.5-1.5 microm. In some cases, the larger intracellular Cx43-GFP transport intermediates were observed to form from the internalization of gap junctions, whereas the smaller transport intermediates may represent other routes of trafficking to or from the plasma membrane. The localization of Cx43-GFP in two transport compartments suggests that the dynamic formation and turnover of connexins may involve at least two distinct pathways.
A study was performed to identify variables that affected cause-specific survival (CSS) and local relapse-free rate (LRFR) in patients with differentiated thyroid cancer (DTC) and extrathyroid ...extension (ETE) and to examine the role of external beam radiotherapy (XRT). Prognostic factors were similar to those found in studies of all patients with DTC. In patients with postoperative gross residual disease treated with radiotherapy, 10-year CSS and LRFR were 48% and 90%. For patients with no residual or microscopic disease, 10-year CSS and LRFR were 92% and 93%. In patients older than 60 years with T3 ETE but no gross residual disease postoperatively there was an improved LRFR at 5 years of 96%, compared to 87.5% without XRT (P=.02). Patients with gross ETE benefit from XRT and there may be a potential benefit in reducing locoregional failure in patients over 60 years with minimal extrathyroidal extension (T3).
•Absolute percentage of pattern 4 can be estimated (eAPP4) even without overall pattern 4 percentage reported on synoptic pathology.•eAPP4 correlated well with clinical outcomes in patients with ...intermediate risk treated with low-dose-rate prostate brachytherapy monotherapy.•This contributes to a growing body of evidence that the resolution of overall Gleason Grade Grouping can be improved by considering the absolute quantity of pattern 4 disease in prostate biopsy specimens.
To determine whether a system to estimate Absolute Percentage of Biopsied Tissue Positive for Gleason Pattern 4 (eAPP4) is useful as a prognostication tool for patients with intermediate risk prostate cancer (IR-PCa) undergoing low dose rate prostate brachytherapy.
497 patients with IR-PCa and known grade group 2 or 3 disease treated with low dose rate seed brachytherapy (LDR-BT) at a quaternary cancer centre were retrospectively reviewed. Prostate biopsies for each patient included Gleason grading with synoptic reporting that did not include percentage of pattern 4 disease found within the sample. Each core was assigned a grade grouping, however, and that was used with optimized estimates of percentage of pattern four disease to estimate eAPP4. Outcomes including cumulative incidence of recurrence (CIR), treatment of recurrent disease (RRX), and metastasis-free survival (MFS) were then reviewed and the prognostic value of eAPP4 evaluated.
428 (86%) patients had Gleason grade group 2 and 69 (14%) patients had Gleason grade group 3 disease. 230 (46%) patients had National Comprehensive Cancer Network (NCCN) favourable intermediate at baseline, while 267 (54%) of patients had NCCN unfavourable intermediate at baseline. Median follow-up was 7.3 (5.5–9.6) years. eAPP4 was predictive of CIR (p = 0.003), RRX (p = 0.003), or MFS (p = 0.001) events, while Gleason grade grouping alone was not. eAPP4 was strongest as a predictor for MFS when estimates of 30% (grade group 2) and 80% (grade group 3) were used HR 1.07 (1.03–1.12); p = 0.001.
eAPP4 was strongly predictive of recurrence and metastasis-free survival in a large cohort of patients receiving LDR-BT treatment for IR-PCa. Treatment of future patients with IR-PCa could include the use of eAPP4 prognostication.
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