Is Substantial Lymphovascular Space Invasion Prognostic for Clinical Outcomes in Type II Endometrial Cancer?

AIMS: Substantial lymphovascular space invasion (LVSI) compared with none or focal LVSI is predictive of lymph node involvement and worse clinical outcomes in endometrioid-type endometrial carcinoma. We aimed to quantify the incidence of substantial LVSI in type II (clear cell and serous) endometrial cancer and correlate the extent of LVSI with clinical outcomes. MATERIALS AND METHODS: A retrospective review was conducted on type II endometrial cancer patients who underwent surgical management from July 2017 to December 2019 using the three-tier LVSI scoring system. Binary logistic regression and Cox regression were used to analyse predictors of lymph node involvement or survival outcomes, respectively. The Kaplan-Meier method and Log-rank test were used to analyse differences in locoregional disease-free survival (LR-DFS), distant metastasis disease-free survival (DM-DFS) and overall survival between patients with substantial versus none/focal LVSI. RESULTS: In 79 patients with type II endometrial carcinoma, no LVSI, focal LVSI and substantial LVSI was present in 48.1%, 15.2% and 36.7% of patients, respectively. Lymph nodes were involved in 0.0% with no LVSI, 20.0% with focal LVSI and 60.0% with substantial LVSI (P < 0.001). The median follow-up was 22.2 months. In patients with none/focal versus substantial LVSI, the 2-year LR-DFS and DM-DFS rates were 91.5% versus 71.4% (P = 0.01) and 90.2% versus 63.8% (P = 0.005), respectively. On univariate analysis, myometrial invasion ≥50%, tumour size ≥3.6 cm, substantial versus none/focal LVSI, lymph node involvement and omission of adjuvant radiotherapy were significant predictors for worse LR-DFS and DM-DFS (P < 0.05). DISCUSSION: Substantial LVSI has a high incidence in type II pathology at our institution and predicts for lymph node involvement and worse clinical outcomes.

Evaluating the Tolerability of a Simultaneous Focal Boost to the Gross Tumor in Prostate SABR: A Toxicity and Quality-of-Life Comparison of Two Prospective Trials.

PURPOSE: Dose-escalated stereotactic ablative radiotherapy (SABR) to the whole prostate may be associated with better outcomes but has a risk of increased toxicity. An alternative approach is to focally boost the dominant intraprostatic lesion (DIL) seen on magnetic resonance imaging. We report the toxicity and quality-of-life (QOL) outcomes of 2 phase 2 trials of prostate and pelvic SABR, with or without a simultaneous DIL boost. METHODS AND MATERIALS: The first trial treated patients with high-risk prostate cancer to a dose of 40 Gy to the prostate and 25 Gy to the pelvis in 5 fractions. The second trial treated patients with intermediate-risk and high-risk prostate cancer to a dose of 35 Gy to the prostate, 25 Gy to the pelvis, and a DIL boost up to 50 Gy in 5 fractions. Acute toxicities, late toxicities, and QOL were assessed. RESULTS: Thirty patients were enrolled in each trial. In the focal boost cohort, the median DIL D90% was 48.3 Gy. There was no significant difference in acute grade ≥2 gastrointestinal or genitourinary toxicity between the 2 trials or in cumulative worst late gastrointestinal or genitourinary toxicity up to 24 months. There was no significant difference in QOL domain scores or minimally clinical important change between the 2 trials. CONCLUSIONS: Prostate and pelvic SABR with a simultaneous DIL boost was feasible. Acute grade ≥2 toxicity, late toxicity, and QOL seemed to be comparable to a cohort that did not receive a focal boost. Further follow-up will be required to assess long-term outcomes, and randomized data are required to confirm these findings.

Stereotactic Body Radiotherapy versus Low Dose Rate Brachytherapy for Localised Prostate Cancer: a Cost-Utility Analysis.

AIMS: To conduct a cost-utility analysis comparing stereotactic body radiotherapy (SBRT) with low dose rate brachytherapy (LDR-BT) for localised prostate cancer (PCa). MATERIALS AND METHODS: A decision-analytic Markov model was developed from the healthcare payer perspective to simulate the history of a 66-year-old man with low-risk PCa. The model followed patients yearly over their remaining lifetimes. Health states included 'recurrence-free', 'biochemical recurrence' (BR), 'metastatic' and 'death'. Transition probabilities were based on a retrospective cohort analysis undertaken at our institution. Utilities were derived from the literature. Costs were assigned in 2015 Canadian dollars ($) and reflected Ontario's health system and departmental costs. Outcomes included quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratios. A willingness-to-pay threshold of $50 000/QALY was used. RESULTS: SBRT was the dominant strategy with 0.008LYs and 0.029QALYs gained and a reduction in cost of $2615. Under base case conditions, our results were sensitive to the BR probability associated with both strategies. LDR-BT becomes the preferred strategy if the BR with SBRT is 1.3*[baseline BR_SBRT] or if the BR with LDR-BT is 0.76*[baseline BR_LDR-BT]. When assuming the same BR for both strategies, LDR-BT becomes marginally more effective with 0.009QALYs gained at a cost of $272 848/QALY. CONCLUSIONS: SBRT represents an economically attractive radiation strategy. Further research should be carried out to provide longer-term follow-up and high-quality evidence.

Dose-escalation of five-fraction SABR in prostate cancer: Toxicity comparison of two prospective trials.

PURPOSE: To compare biochemical outcome and toxicities of two prospective 5-fraction stereotactic ablative radiotherapy (SABR) studies in prostate cancer. MATERIALS AND METHODS: 84 patients in pHART3 received 35 Gy, 30 patients in pHART6 received 40 Gy in 5-fractions to the prostate alone, once weekly. 4mm and 5mm PTV margins were used, respectively. Biochemical outcome, acute, late and cumulative genitourinary (GU)/gastrointestinal (GI) toxicities were compared. RESULTS: Median follow-up was 74 and 36 months, respectively. Median prostate specific antigen nadir was 0.4 ng/ml and 0.3 ng/ml. 2-, 4- and 6-year biochemical relapse-free survival (bRFS-2+nadir) was 100%, 98.7% and 95.9% in pHART3; 100%, 100% and not reached in pHART6 (p=0.91). There was one acute grade 3 GU (retention) and late grade 4 GI (fistula) toxicity in pHART3, none in pHART6. One patient in each study had persisting grade 2+ toxicity at the last follow-up. pHART6 patients had a greater grade 2+ cumulative GU (5% versus 24.2%) and GI (7.6% versus 26.2%) toxicities. CONCLUSIONS: Patients receiving dose-escalated SABR had slightly lower PSA nadir and similar bRFS, longer follow-up is needed to better estimate biochemical outcomes. There was a greater risk of grade 2 toxicity in pHART6 but not grade 3+ toxicities. Persisting toxicity at the last follow-up is similar.

Stereotactic Ablative Radiotherapy (SABR) in Patients with Medically Inoperable Peripheral Early Stage Lung Cancer: Outcomes for the First UK SABR Cohort.

AIMS: To report outcomes for the first UK cohort treated for early stage peripheral lung cancer using stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS: Patients were included who received SABR between May 2009 and May 2012. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. Patients were treated according to the UK SABR Consortium Guidelines. Univariate and multivariate Cox regression was used to determine factors that influenced overall survival and local control. RESULTS: In total, 273 patients received SABR for 288 lesions in the time period examined. The median follow-up was 19.7 months. The median overall survival for all patients was 27.3 months, with 1, 2 and 3 year overall survival of 78.0, 54.9 and 38.6%, respectively. The 1, 2 and 3 year rates of local control were 98.2, 95.7 and 95.7%, respectively. All patients completed the planned course of treatment and rates of Common Toxicity Criteria grade 3+ toxicity were low. On multivariate analysis, patients with Medical Research Council (MRC) breathlessness scores of 3-5 had worse overall survival compared with patients with scores of 1-2 (hazard ratio: 2.10; 95% confidence interval: 1.25-3.59) and the presence of histological diagnosis conferred improved overall survival (hazard ratio: 0.54; 95% confidence interval: 0.31-0.93), probably reflecting that patients who are considered well enough to undergo biopsy are generally fitter overall. No factors were identified that significantly influenced local control. CONCLUSIONS: SABR is an effective and well-tolerated treatment option for patients with early stage peripheral lung cancer who are not suitable for surgery. No patient cohort was identified in whom SABR was considered inappropriate. This series adds to the existing positive data that support SABR for this patient group.

Metastatic Prostate Cancer in Men Initially Treated with Active Surveillance.

PURPOSE: Active surveillance is an approach to low and low intermediate risk prostate cancer that is designed to decrease overtreatment. Despite close monitoring a small subset of patients progress to metastatic disease. We analyzed the clinical and pathological correlates of surveillance in patients who eventually experienced metastasis. MATERIALS AND METHODS: This was a single center, prospective cohort study. Eligible patients were treated with an expectant approach. The main outcome measure was metastasis-free survival. Predictive factors for metastasis were identified. RESULTS: Metastasis developed in 30 of 980 patients, of whom 211 were classified at intermediate risk, including 14 who progressed to metastatic disease. Median followup was 6.3 years, median age was 70 years, median prostate specific antigen was 6.2 ng/ml and median time to metastasis was 8.9 years. Metastases developed in bone in 18 patients (60%) and in lymph nodes in 13 (43%). Prostate specific antigen doubling time less than 3 years (HR 3.7, 95% CI 1.4-9.4, p = 0.0006), Gleason score 7 (HR 3.0, 95% CI 1.2-7.3, p = 0.0018) and a total of 3 or more positive cores (HR 2.7, 95% CI 1.1-6.8, p = 0.0028) were independent predictors of metastasis. Although the intermediate risk group was at higher risk for metastasis, those with Gleason score 6 and prostate specific antigen greater than 10 ng/ml were not at increased risk for metastasis. Metastasis developed in only 2 patients with Gleason score 6 and neither had surgical pathology grading. CONCLUSION: Active surveillance appears safe in patients at low risk and in select patients at intermediate risk, particularly those with Gleason score 6 and prostate specific antigen greater than 10 ng/ml. Patients with elements of Gleason pattern 4 on diagnostic biopsy are at increased risk for eventual metastasis when treated with an initial conservative approach.

The Effect of Dose and Quality Assurance in Early Prostate Cancer Treated with Low Dose Rate Brachytherapy as Monotherapy.

AIMS: To examine the relationship between post-implant computed tomography dosimetry and long-term prostate-specific antigen relapse-free survival in patients treated with iodine 125 (I-125) low dose rate prostate brachytherapy as monotherapy and, second, to audit recent practice against Royal College of Radiologists' (RCR) guidelines after the re-introduction of post-implant dosimetry for all patients in our centre. MATERIALS AND METHODS: Between March 1995 and September 2007, 2157 consecutive patients with localised prostate cancer underwent I-125 permanent prostate brachytherapy as monotherapy in a single UK centre. All patients were transrectal ultrasound planned delivering a 145 Gy (TG 43) minimum peripheral dose. None received supplemental external beam radiotherapy. Post-implant computed tomography-based dosimetry was undertaken between 4 and 6 weeks after treatment and was available for 711 (33%). Outcomes were analysed in terms of the relationship of D90 to prostate-specific antigen relapse-free survival (nadir 2+ definition) and all patients had a minimum follow-up of 5 years. For contemporary patients from 2011, quality metrics from post-implant computed tomography as defined by RCR guidelines are presented. RESULTS: A mean D90 of 138.7 Gy (standard deviation 24.7) was achieved for the historic cohort. Biochemical control at 10 years was 76% in patients with D90 > 140 Gy and 68% in those with D90 < 140 Gy (P < 0.01). In current practice, over the last 3 years the mean (standard deviation) D90 has increased from 154 (15.3) Gy in 2011 to 164 (13.5) Gy in 2013. Similarly, an increase in the mean (standard deviation) V100 from 92 (4.4) to 95 (3.2) % is noted over time. No difference between clinicians was noted. CONCLUSION: D90 values of less than 140 Gy continue to be predictive of increased risk of recurrence of prostate cancer across risk groups with longer follow-up. Quality assurance can be used to ensure improved and consistent implant quality in a team with multiple clinicians.

Clinical trials of stereotactic ablative radiotherapy for prostate cancer: updates and future direction.

Stereotactic body radiotherapy, also known as stereotactic ablative body radiotherapy (SABR), is an emerging treatment option for lung, prostate, liver and other tumors. Key factors in SABR are delivery of a high-dose radiation per fraction, proper patient positioning and target localization. Our review details the various radiotherapy techniques, dose fractionation schedules and toxicities for prostate SABR. Ongoing Phase II/III SABR studies across various risk groups have been included. It also discusses the role of conscientious focal dose escalation of the dominant intraprostatic nodule, integrating multiparametric MRI into radiotherapy protocols and finally cost-effectiveness of SABR.

Second primary cancers occurring after I-125 brachytherapy as monotherapy for early prostate cancer.

AIMS: Prostate brachytherapy may be associated with a lower risk of radiation-induced second primary cancer (SPC) as a significantly smaller volume of normal tissue is irradiated when compared with external beam techniques. Limited data are available as it has been a routine treatment option for less than 20 years. This study identified cases of SPC in patients who underwent I-125 prostate brachytherapy as monotherapy in a single institution. MATERIALS AND METHODS: SPC incidence was retrieved by conducting a UK cancer registry search (Northern and Yorkshire Cancer Registry and Information Service) for 1805 consecutive patients with localised prostate cancer who received monotherapy with I-125 brachytherapy from 1995 to 2006 at a single public hospital. Of 1730 UK residents, the completeness of the registry match was 91% (1574 patients). The mean age at treatment (interquartile range) of the cohort was 63 (58-68) years with 1100 patients (70%) over the age of 60 years at treatment. The median (range) follow-up was 8 (6-10) years with 487 patients (31%) having 10 years or more. RESULTS: In total, 170 patients (10.8%) were diagnosed with second primaries (1 year or more after implant); 20 of these were bladder and 10 rectal cancers. The 10 year cumulative incidences were 14.6, 1 and 0.84% for any second malignancy, bladder and rectal cancer, respectively. Only the standardised incidence rate (SIR) for bladder cancer was higher at 1.54 (95% confidence interval 0.96-2.46) compared with the general population. The SIR for bladder cancer was higher in the first few years after treatment, suggesting that the increased incidence of bladder cancer is due to increased urological surveillance. CONCLUSIONS: Overall, the incidence of SPC after I-125 is comparable with other published data with no significant excess more than 5 years from treatment. Mortality secondary to SPC of the bladder or rectum is unusual.