Local-only Recurrence Research Articles

Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: an international multicentre retrospective cohort study.

Most patients undergoing pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) develop recurrence. No previous studies have investigated predictors of local-only recurrence following PD for PDAC. Our study aimed to determine timing, pattern and predictors of any-site and local-only recurrence following PD for PDAC. Patients who underwent PD for PDAC between June 2012 and May 2015 (29 centres, eight countries) were included. The primary outcome was recurrence pattern (none, local-only, distant-only or mixed local/distant). Data were collected on demographics, comorbidities, investigations, operation details, complications, histology, adjuvant therapies, recurrence and survival. Univariable tests and regression analysis investigated factors associated with any-site and local-only recurrence. Of 866 patients, 573 (66 %) developed recurrence: 170 (20 %) developed local-only recurrence, 164 (19%) developed mixed local/distant recurrence, and 239 (28 %) developed distant-only recurrence. Local-only or lung-only recurrence had a more favourable prognosis than other recurrence patterns. Predictors of any-site recurrence were preoperative biliary stenting, venous resection and poorly-differentiated, node-positive tumours. Predictors of local-only recurrence were preoperative radiological lymphadenopathy, well-differentiated tumours, fewer than 15 resected lymph nodes and intraoperative blood transfusion. Ensuring radical resection and avoiding intraoperative blood transfusion may reduce the risk of local-only recurrence following PD for PDAC.

Definition and Predictors of Early Recurrence in Neoadjuvantly Treated Esophageal and Gastroesophageal Adenocarcinoma: a Dual-Center Retrospective Cohort Study.

BACKGROUND: Early recurrence after esophagectomy is often used as a surrogate for aggressive tumor biology and treatment failure. However, there is no standardized definition of early recurrence, and predictors for early recurrence are unknown. Therefore, we aimed to define an evidence-based cutoff to discriminate early and late recurrence and assess the influence of neoadjuvant treatment modalities for patients with esophageal or gastroesophageal-junction adenocarcinoma (EAC). This dual-center retrospective cohort study included patients who underwent esophagectomy for stage II-III EAC after neoadjuvant treatment with chemotherapy using 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) or radiochemotherapy according to the Chemoradiotherapy for Esophageal Cancer followed by Surgery Study (CROSS)protocol from 2012 to 2022. The optimal cutoff for early versus late recurrence was calculated by using the most significant difference in survival after recurrence (SAR). Multivariable logistic regression was used to identify variables associated with early recurrence. Of 334 included patients, 160 (47.9%) were diagnosed with recurrence. Most patients had systemic (60.5%) or multiple sites of recurrence (21.1%), whereas local-only recurrence (9.2%) and carcinomatosis (9.2%) were rare. The optimal interval between surgery and recurrence for distinguishing early and late recurrence was 18 months (median SAR: 9.1 versus 17.8 months, p = 0.039) with only 24% of recurrences diagnosed after the calculated cutoff. Advanced pathologic tumor infiltration (ypT3-4, p = 0.006), nodal positivity (p = 0.013), poor treatment response (>10% residual tumor, p = 0.015), and no adjuvant treatment (p = 0.048) predicted early recurrence. Early recurrence can be defined as recurrent disease within 18 months. Hallmarks for early recurrence are poor response to neoadjuvant therapy with persisting advanced disease. In those patients, adjuvant therapy and closer follow-up should be considered.

765. PATTERNS, TIMING, AND SURVIVAL OF RECURRENCE FOLLOWING SURGERY FOR ESOPHAGEAL ADENOCARCINOMA IN THE EUROPEAN MULTICENTRE ENSURE STUDY

Abstract Background After surgery for esophageal cancer approximately half of patients will develop disease recurrence. A more accurate and detailed understanding of the pattern, timing, treatment and prognosis of initial recurrence sites can guide improvements in surveillance and therapy. Therefore, the aim of this study was to accurately describe the pattern and timing of esophageal cancer recurrence, and to assess the distinct survival patterns of these recurrence locations. Methods This study included all patients who underwent surgical resection for esophageal and junctional adenocarcinoma registered in the ENSURE study. ENSURE was an international multicenter study of consecutive patients undergoing surgery for esophageal and esophagogastric junction cancers between 2009 and 2015 across 20 centers in Europe and Canada (NCT03461341). The first recurrence site was recorded and recurrence-free survival (RFS) was estimated using Kaplan-Meier curves. Sites of first recurrence were stratified into different groups and survival outcomes post recurrence detection were estimated using Kaplan-Meier curves. Results Of 3397 eligible patients, 1310 patients had disease recurrence with comprehensive follow-up data available (median RFS of 12.1 months). First recurrence was detected at multiple distant sites (n=469; 37.3%) or at a single distant site (n=463; 33.7%), while isolated local recurrence occurred in 189 (14.4%) patients. Liver-only recurrence occurred significantly earlier (median 9.0 months), while lung-only (15.2 months) and local-only occurred later (17.8 months). Patients with multiple-sites and liver-only recurrence had significant worse median post recurrence survival (7.4 and 8.3 months, respectively) when compared with lung- or local-only recurrence (10.4 and 15.9 months, respectively). Conclusion This study demonstrates that specific recurrence locations of esophageal cancer possess distinct RFS curves. Furthermore, specific recurrence locations result in different post recurrence survival outcomes. This information can help guide improvements in surveillance after esophageal cancer surgery and decisions regarding treatment of esophageal cancer recurrence.

Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for distal cholangiocarcinoma: An international multicentre retrospective cohort study

IntroductionPatients undergoing pancreaticoduodenectomy for distal cholangiocarcinoma (dCCA) often develop cancer recurrence. Establishing timing, patterns and risk factors for recurrence may help inform surveillance protocol strategies or select patients who could benefit from additional systemic or locoregional therapies. This multicentre retrospective cohort study aimed to determine timing, patterns, and predictive factors of recurrence following pancreaticoduodenectomy for dCCA. Materials and methodsPatients who underwent pancreaticoduodenectomy for dCCA between June 2012 and May 2015 with five years of follow-up were included. The primary outcome was recurrence pattern (none, local-only, distant-only or mixed local/distant). Data were collected on comorbidities, investigations, operation details, complications, histology, adjuvant and palliative therapies, recurrence-free and overall survival. Univariable tests and regression analyses investigated factors associated with recurrence. ResultsIn the cohort of 198 patients, 129 (65%) developed recurrence: 30 (15%) developed local-only recurrence, 44 (22%) developed distant-only recurrence and 55 (28%) developed mixed pattern recurrence. The most common recurrence sites were local (49%), liver (24%) and lung (11%). 94% of patients who developed recurrence did so within three years of surgery. Predictors of recurrence on univariable analysis were cancer stage, R1 resection, lymph node metastases, perineural invasion, microvascular invasion and lymphatic invasion. Predictors of recurrence on multivariable analysis were female sex, venous resection, advancing histological stage and lymphatic invasion. ConclusionTwo thirds of patients have cancer recurrence following pancreaticoduodenectomy for dCCA, and most recur within three years of surgery. The commonest sites of recurrence are the pancreatic bed, liver and lung. Multiple histological features are associated with recurrence.

Impact of intrapulmonary tumour location of non-small-cell lung cancer on surgical outcomes for segmentectomy.

While segmentectomy is considered a viable option for small peripheral non-small-cell lung cancer, its efficacy for central lesions remains uncertain. This study aimed to assess the oncological outcomes of segmentectomy for central lesions compared to peripheral ones. We retrospectively examined 338 clinical stage IA non-small-cell lung cancer patients who underwent thoracoscopic anatomical segmentectomy at our institution from January 2013 to December 2021. Patients were divided into 2 groups based on intrapulmonary tumour location: inner two-thirds (central group, n = 82) and outer one-third (peripheral group, n = 256). The gender, body mass index, performance score, smoking, comorbidities and preoperative pulmonary function were similar in both groups. On computed tomography images, tumour diameter and consolidation-to-tumour ratio were comparable between the groups. The central group had significantly greater tumour-to-pleura distances [mm, 23 (18-27) vs 11 (8-14); P < 0.001], shorter margin distances [mm, 20 (15-20) vs 20 (20-20); P < 0.001] and larger resected lung volumes based on subsegment count [4 (3-6) vs 3 (3-5); P = 0.004] than the peripheral group. Surgery duration, bleeding, hospitalization or drainage period, mortality, readmission and pathological stage were equivalent between the groups. The central group showed significantly more postoperative pleural effusions (5% vs 1%; P = 0.03) than the peripheral group, with no adverse impact on postoperative pulmonary functions. During the follow-up period, local-only recurrence rates were 0% and 8% in the respective groups (Gray test P = 0.07), and total recurrence rates were 6% and 11% (Gray test P = 0.70), with no significant differences. Moreover, no significant inter-group difference in overall survival rates was observed (82% vs 93%; P = 0.15). Segmentectomy may be a promising therapeutic option for early-stage non-small-cell lung cancer located in the inner two-thirds of the parenchyma.

Progression of Site-specific Recurrence of Pancreatic Cancer and Implications for Treatment.

To analyze postrecurrence progression in the context of recurrence sites and assess implications for postrecurrence treatment. Most patients with resected pancreatic ductal adenocarcinoma (PDAC) recur within 2 years. Different survival outcomes for location-specific patterns of recurrence are reported, highlighting their prognostic value. However, a lack of understanding of postrecurrence progression and survival remains. This retrospective analysis included surgically treated patients with PDAC at NYU Langone Health (2010-2021). Sites of recurrence were identified at the time of diagnosis and further follow-up. Kaplan-Meier curves, log-rank test, and Cox regression analyses were applied to assess survival outcomes. Recurrence occurred in 57.3% (196/342) patients with a median time to recurrence of 11.3 months (95% CI: 12.6-16.5). The first site of recurrence was local in 43.9% of patients, liver in 23.5%, peritoneal in 8.7%, lung in 3.6%, whereas 20.4% had multiple sites of recurrence. Progression to secondary sites was observed in 11.7%. Only lung involvement was associated with significantly longer survival after recurrence compared with other sites (16.9 vs 8.49 months, P = 0.003). In local recurrence, 21 (33.3%) patients were alive after 1 year without progression to secondary sites. This was associated with a CA19-9 of <100 U/mL at the time of primary diagnosis ( P = 0.039), nodal negative disease ( P = 0.023), and well-moderate differentiation ( P = 0.042) compared with patients with progression. Except for lung recurrence, postrecurrence survival after PDAC resection is associated with poor survival. A subset of patients with local-only recurrence do not quickly succumb to systemic spread. This is associated with markers for favorable tumor biology, making them candidates for potential curative re-resections when feasible.

Clinical Usefulness of PSMA PET/CT Imaging in Patients with Suspected Recurrence of Prostate Cancer after Primary RT with PSA below the Phoenix Criteria Threshold: Systematic Review and Meta-Analysis

To assess the detection rate and the patterns of PSMA PET/CT uptake in patients with suspected prostate cancer recurrence after primary radiotherapy with serum PSA levels below the accepted Phoenix definition criteria for biochemical recurrence. The meta-analysis was performed according to the PRISMA statement. Studies providing data on patients with suspected prostate cancer recurrence after primary radiotherapy with serum PSA levels below the accepted Phoenix definition criteria were included. Atotal of 5 studies included a total of 1334 patients, of which 489 patients with suspected BCR and serum PSA levels below the Phoenix criteria were included. The PSMA PET/CT detection rate (DR) was 60% for PSA <0.5 ng/mL, 76% for PSA 0.5-1 ng/mL, 81.03% for PSA 1-2 ng/mL, and 89.5% for PSA>2. No significant differences were found in the locations of PSMA-PET/CT uptake among those with PSA ≤2 ng/mL, compared with those meeting the Phoenix criteria. The PSMA-PET/CT uptake of local-only recurrence was more likely in patients with PSA <2 ng/mL (local-only recurrence PSA >2 ng/mL [40.07%] vs PSA <2 ng/mL [58.10%]), RR: 0.718 (95% CI: 0.579-0.892). Lymph node, bone, and visceral metastasis detection rates could be extracted from 3 studies (432 patients). For lymph nodes, the DR was 46% (95% CI: 38-54) in patients outside the Phoenix criteria threshold, and 50% (95% CI: 39-62) in patients with PSA>2 ng/mL. The DR for bone metastases was 19% (95% CI: 12-28) in patients outside the Phoenix criteria threshold, and 25% (95% CI: 19-31) in patients with PSA>2 ng/mL. The DR for visceral metastases was 3% (95% CI: 0-7) in patients outside the Phoenix criteria threshold, and 2% (95% CI: 0-4) in patients with PSA>2 ng/mL. The potentially salvageable disease was considered when all evidence of avid disease could be safely treated with local therapy. This data could be extracted from two studies (343 patients). A higher proportion of disease potentially amenable to salvage therapy was reported in patients outside the Phoenix criteria threshold [salvageable disease: PSA ≤2 ng/mL: 69% (95% CI: 57-80), and PSA >2 ng/mL: 61% (95% CI: 55-66). The pooled risk ratio meta-analysis showed no statistically significant differences between the two previous groups RR: 0.91 (95% CI: 0.75-1.10). PSMAPET/CT can detect prostate cancer recurrence in patients with PSA levels below the Phoenix criteria threshold (reaching up to 80%). Local-only recurrence detection by PSMA PET/CT was more likely in patients with PSA <2 ng/mL. The data from the present meta-analysis shows that a critical review of the Phoenix criteria in the era of PSMA PET/CT might be warranted. Nevertheless, the lack of anatomopathological validation and the retrospective nature of the studies are some of our limitations.

Clinical Usefulness of Prostate-specific Membrane Antigen-ligand Positron Emission Tomography/Computed Tomography for the Detection of Prostate Cancer Biochemical Recurrence after Primary Radiation Therapy in Patients with Prostate-specific Antigen Below the Phoenix Threshold: Systematic Review and Meta-analysis

AimsAfter primary radiotherapy, biochemical recurrence is defined according to the Phoenix criteria as a prostate-specific antigen (PSA) value >2 ng/ml relative to the nadir. Several studies have shown that prostate-specific membrane antigen (PSMA)-ligand positron emission tomography/computed tomography (PET/CT) can help in detecting recurrence in patients with low PSA values. This study aimed to assess the detection rate and patterns of PSMA-ligand PET/CT uptake in patients with suspected biochemical recurrence after primary radiotherapy and with PSA levels below the Phoenix threshold. Materials and methodsThe meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Articles providing data on patients with suspected prostate cancer recurrence after primary radiotherapy with a PSA value below the Phoenix threshold and who underwent PSMA-ligand PET/CT were included. Quality assessment was carried out using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). ResultsIn total, five studies were included, recruiting 909 patients (202 with PSA ≤2 ng/ml). The PSMA-ligand detection rate in the patients with ≤2 ng/ml ranged from 66 to 83%. The most frequent source of PSMA-ligand PET/CT uptake was local recurrence, followed by lymph node metastasis and bone metastasis. PSMA-ligand PET/CT uptake due to local-only recurrence was more likely in patients with PSA ≤2 ng/ml compared with PSA > 2 ng/ml: risk ratio 0.72 (95% confidence interval 0.58–0.89), P = 0.003. No significant differences were observed in the detection of PSMA-ligand uptake in other areas. Limitations include a lack of biopsy confirmation, cohort reports with small sample sizes and a potentially high risk of bias. ConclusionA significant detection of PSMA-ligand-avid disease was observed in patients with PSA levels below the Phoenix threshold. There was a higher likelihood of detecting local-only uptake when the PSA value was ≤2 ng/ml. The findings suggest that a critical review of the Phoenix criteria may be warranted in the era of PSMA-ligand PET/CT and highlight the need for further prospective trials.

Local salvage of radiorecurrent prostate cancer.

Locally recurrent prostate cancer following primary external beam radiotherapy without distant metastasis is a challenging problem, with no current consensus on the optimal management of these patients. Traditional whole-gland salvage treatments offered up to a 50% 5-year disease-free survival rate but with troubling levels of risk for significant complications. Recent progress in advanced imaging techniques has allowed a more accurate selection of patients with local-only recurrence and a selection of patients that may be suitable for newer partial-gland salvage treatments that may reduce late complications. This article reviews advances in patient selection and provides an overview of whole- and partial-gland salvage results from selected recent meta-analyses, multi-institutional series, and studies from centers of excellence for these treatment approaches. Salvage radical prostatectomy produces 5-year relapse-free survival (RFS) rates in the 50%-60% range with severe gastrointestinal (GI) toxicity in < 2% but severe genitourinary (GU) toxicity in 15%-23% of patients. The whole-gland options of high and low dose rate brachytherapy and stereotactic body radiation therapy appear to offer similar 5-year control rates, with low severe GU and GI toxicity rates of 4%-8% and <2%, respectively. Cryotherapy and high-intensity focused ultrasound (HIFU) offer similar 5-year RFS rates but carry significant risks for severe GU and GI toxicity in the range of 10%-27% and <2%, respectively. Early results of partial-gland salvage techniques in selected patients appear promising, with 3-year RFS rates of 48%-72% and rare grade 3 toxicity. It is important to understand the relative effectiveness and risks of the various treatment options to effectively counsel patients who face this distressing clinical situation. Whole-gland salvage options offer the possibility of long-term control but with significant risks of severe toxicity. Emerging data for the partial-gland salvage options in appropriately selected patients may offer hope of reasonable control rates with reduced severe toxicity.

Predictors of Local-only Recurrence Following Pancreatoduodenectomy for Pancreatic Cancer: Results from the Recurrence After Whipple’s (RAW) International Cohort Study

Predictors of Local-only Recurrence Following Pancreatoduodenectomy for Pancreatic Cancer: Results from the Recurrence After Whipple’s (RAW) International Cohort Study

Magnetic Resonance-Guided Reirradiation for Local Recurrence within the Prostate or in the Prostate Bed: One-Year Clinical Results of a Prospective Registry Study.

Simple SummaryMRI-guided radiotherapy (MRgRT) is a new technique of radiotherapy. We evaluated this treatment for the reirradiation of patients with local-only recurrence of prostate cancers. The objectives were to evaluate the tolerance and the first clinical results in a cohort of 37 patients with a 1-year follow-up. The treatment was well tolerated with no grade > 2 acute toxicities and only one (3%) grade 3 late toxicity (hematuria). The clinical results were promising with a six, nine and 12-months biochemical-recurrence free survival of 97.3%, 86.5% and 65.0%, respectively. In conclusion, MRI-guided reirradiation might become an interesting option for the treatment of locally recurrent prostate cancers.Around 33% of patients treated by EBRT or brachytherapy will present a biochemical recurrence. SBRT is a new option for the treatment of patients with local-only recurrence. MRgRT seems to be interesting for the treatment of these recurrences. This article presents the one-year late tolerance and biochemical recurrence-free survival results of a prospective registry study. Patients with intraprostatic (or in the prostate bed) recurrence were treated with 5 to 9 fractions (median dose of 30 Gy in 5 fractions) with the MRIdian® system. PSA level and toxicities were evaluated before treatment and at three, six and 12 months after treatment. Thirty-seven patients with a median age of 74.5 years old were treated between 21 October 2019 and 7 December 2020. Acute tolerance was excellent with no grade >2 toxicities. Twelve months after treatment, we observed an increase of grade 1–2 dysuria (46% vs. 13% before treatment) and grade 1 polyuria (73% vs. 7%). The six, nine and 12-months biochemical-recurrence free survival were 97.3%, 86.5% and 65.0%. Fifteen patients (40%) presented a biochemical recurrence. Nine of these 15 patients (60%) had a persistent disease within the treated volume. In conclusion, MRgRT is safe and has promising survival results.

Role of Ki-67, MRE11, and PD-L1 as Predictive Biomarkers for Recurrence Pattern in Muscle-invasive Bladder Cancer.

Muscle invasive bladder cancer (MIBC) is an aggressive disease with high rates of local recurrence following radical cystectomy (RC). Currently, there are no clinically validated biomarkers to predict local only recurrence (LOR) and guide adjuvant treatment decisions. This pilot study evaluated the role of Ki-67, MRE11 and PD-L1 as predictive biomarkers for recurrence patterns in patients undergoing RC for MIBC. Our institutional cystectomy database containing cases from 1992-2014 was queried for patients with local only recurrence (LOR), and case-matched to patients with distant recurrence (DR) and no recurrence (NR). Clinicopathological data were collected and a tissue microarray was analyzed for presence of Ki-67, MRE11, and PD-L1 using immunofluorescence and immunohistochemistry. Pathologic specimens from 42 patients (18 NR, 16 LOR, and 8 DR) were reviewed. Compared to normal bladder tissue, tumors had increased expression of Ki-67 (p<0.01) and PD-L1 (p<0.05). High Ki-67 was associated with recurrence pattern (local vs. distant) on univariate analysis (p<0.05). Ki-67 cell density varied by recurrence type: LOR (1354 cells/mm2), DR (557 cells/mm2) and NR (1111 cells/mm2) (p=0.034). Our selected biomarkers could distinguish MIBC from normal bladder tissue but could not classify samples by recurrence pattern.

Percutaneous ablation of post-surgical solitary early recurrence of colorectal liver metastases is an effective "test-of-time" approach.

Standard treatment of early recurrence of colorectal liver metastases (CLM) after liver resection (LR) is chemotherapy followed by loco-regional therapy. We reviewed the outcome of a different strategy ("test-of-time" approach): upfront percutaneous ablation without chemotherapy. Twenty-six consecutive patients with early solitary liver-only recurrence amenable to both resection and ablation (< 30mm, distant from vessels) undergone "test-of-time" approach were analyzed. Early recurrence had a median size of 17mm and occurred after a median interval from LR of 4months. Primary efficacy rate of ablation was 100%. Five patients are alive and disease-free after a mean follow-up of 46months. Five patients had local-only recurrence; all had repeat treatment (LR = 4; Ablation = 1) without chemotherapy. Local recurrence risk was associated with incomplete ablation of 1-cm thick peritumoral margin. The remaining 16 patients had non-local recurrence, 13 early after ablation. Overall, six (23%) patients had ablation as unique treatment and 13 (50%) avoided or postponed chemotherapy (mean chemotherapy-free interval 33.5months). Ablation without chemotherapy of early liver-only recurrence is a reliable "test-of-time" approach. It minimized the invasiveness of treatment with good effectiveness and high salvageability in case of local failure, avoided worthless surgery, and saved chemotherapy for further disease progression.

Radiographic patterns of first disease recurrence after neoadjuvant therapy and surgery for patients with resectable and borderline resectable pancreatic cancer

BackgroundMore than 70% of patients with localized pancreatic cancer treated with upfront surgery develop disease recurrence. Herein we describe the radiographic patterns and timing of disease recurrence after neoadjuvant therapy and surgery in patients with pancreatic cancer. MethodsRadiographic patterns of first disease recurrence were examined in patients with localized pancreatic cancer who completed neoadjuvant therapy and surgery. Disease recurrence was classified as local (pancreas, resection bed, or peripancreatic vasculature); regional (peritoneum or abdominal wall); or distant (liver, lung, bone). Progression-free survival was calculated from the date of diagnosis to the date of recurrence. ResultsOf 306 consecutive patients who completed neoadjuvant therapy and surgery, 149 (49%) had resectable pancreatic cancer and 157 (51%) had borderline resectable disease. Neoadjuvant therapy consisted of chemoradiation (32%), chemotherapy (14%), or both therapies (54%). Overall, primary therapy (including preoperative and postoperative therapy) consisted of chemoradiation alone in 29 (9%), chemotherapy alone in 14 (5%), and both therapies in 263 (86%) patients. At a median follow-up of 27 months, 186 (61%) of the 306 patients had recurrent pancreatic cancer. Sites of first recurrence were local-only in 29 (9%), regional-only in 19 (6%), distant-only in 87 (28%), and multisite in 51 (17%). The overall median progression-free survival for all patients was 24 months. Neoadjuvant chemoradiation reduced the odds of local-only recurrence (odds ratio: 0.21; 95% confidence interval: 0.06–0.77; P = .02). ConclusionAfter neoadjuvant therapy and surgery, 9% of patients were found to have local-only recurrence. Treatment sequencing that incorporates neoadjuvant chemoradiation may improve local disease control.

Multi-institutional Evaluation of Curative Intent Chemoradiotherapy for Patients With Clinical T1N0 Esophageal Adenocarcinoma

PurposeTo evaluate the safety and efficacy of definitive chemoradiotherapy (CRT) for patients with clinical T1N0M0 esophageal adenocarcinoma. Methods and MaterialsThis was a retrospective study of patients with clinical T1N0 adenocarcinoma of the esophagus treated with curative-intent CRT between 2004 and 2017 at 2 tertiary care centers. Patients received CRT instead of esophagectomy owing to medical comorbidities or patient preference. Toxicities were evaluated according to Common Terminology Criteria for Adverse Events version 4.03. The Kaplan-Meier method was used to estimate overall, progression-free, and disease-specific survivals. ResultsTwenty-eight patients were included for analysis. Median age was 76 years (range 55-90). The majority of patients were male (93%) and had a history of Barrett’s esophagus (71%). Tumor characteristics included distal esophagus location (93%), clinical stage T1b (86%), and median length of 2 cm (range, 1-9). Prior endoscopic resection was performed in 57%.The median follow-up was 44 months (range, 4-146). The acute grade 3 adverse events were observed in 7 patients (25%). One patient died of complications potentially related to chemoradiation. Eight patients (29%) had disease progression at a median of 7.6 months after CRT. First site of progression was local only (14%), local and regional (11%), or distant (4%). Salvage locally directed treatment was performed in 3 of 4 patients with local-only recurrence. The 3-year overall survival, progression-free, and disease-specific rates were 78%, 62%, and 81%, respectively. ConclusionCRT is a safe and effective curative treatment strategy for select patients with clinical T1N0M0 esophageal adenocarcinoma.

Can Bladder Cancer Biomarkers from Patients Undergoing Cystectomy Predict the Need for Adjuvant Radiotherapy?

There is a high rate of recurrence of muscle-invasive bladder cancer (MIBC) after cystectomy with local recurrence rates of about 40% and up to 50% distant recurrence. Currently, the inability to predict recurrence patterns limits the use of adjuvant radiotherapy. The ability to use biomarkers to predict local vs distant recurrence could individualize adjuvant therapy. This study evaluates the ability of PD-L1, MRE11 and Ki67 labeling index in radical cystectomy specimens to predict recurrence (no recurrence (NR), local-only recurrence (LOR), and distant recurrence (DR)) in those with MIBC. Our institutional radical cystectomy (RC) database, which includes 2405 cases of urothelial MIBC from 1/1992-12/2014, was queried for LOR. This yielded 119 patients. Of these, pathologic confirmation of disease was available on 20 patients. These were case-matched to 20 NR patients and 20 DR patients. Those without tissue for biomarker staining or adequate follow-up data were excluded. Representative tumor specimens were selected based on H&E slides. Normal bladder tissue adjacent to areas of tumor from RC specimens was also evaluated. A tissue microarray (TMA) was built from formalin fixed, paraffin embedded tissue and analyzed for presence of MRE11, PD-L1 and Ki67 antibodies via immunofluorescence and immunohistochemistry (PD-L1 and Ki67 only). We evaluated pathologic specimens of 42 patients (18 NR, 16 LOR, and 8 DR). The median age of the patients was 69 years. 81% had pT3/pT4 disease, 36% were pN0, and 14% had positive margins. Median follow-up was 147 months. Compared to normal bladder tissue, urothelial cancer cells had higher PDL1 H score, Ki67 H score, % Ki67 on IHC, MRE11 positive cells, MRE11 positive cell density, PD-L1 positive cells, and PD-L1 positive cell density. On univariate analysis, positive surgical margins were more likely to have PD-L1 CPS score >10 and a lower mean Ki67 H score, Ki67 percentage on IHC, PD-L1 positive cells, %PD-L1 positive cells and PD-L1 cell density. Patients with DR had a significantly lower Ki67 mean positive cells (IF) than those with LOR (p=0.04). PD-L1 H score, PD-L1 positive cells and % positive PD-L1 cells were significantly correlated with RFS (p= 0.008, 0.018, 0.015, respectively). On multivariable analysis (MVA), none of the three biomarkers were correlated with LOR/DR, RFS, or OS. PD-L1, MRE11, and Ki67 could discriminate cancer cells from noncancer cells but were unable to predict types of recurrence or clinical cancer outcomes on MVA. Further studies with larger sample size are required to examine the relationship between these biomarkers and bladder cancer recurrence.

Recurrence after neoadjuvant therapy and resection of borderline resectable and locally advanced pancreatic cancer

IntroductionThe incidence, timing, and implications of recurrence in patients who underwent neoadjuvant treatment and surgical resection of borderline resectable (BRPC) or locally advanced (LAPC) pancreatic cancer are not well established. Materials and methodsPatients with BRPC/LAPC who underwent post-neoadjuvant resection between 2007 and 2015 were included. Associations between clinicopathologic characteristics and specific recurrence locations, recurrence-free survival (RFS), and overall survival from resection (OS) were assessed using Cox regression analyses. ResultsFor 231 included patients, median survival from diagnosis and resection were 28.0 and 19.8 months, respectively. After a median RFS of 7.9 months, 189 (81.8%) patients had recurred. Multiple-site (n = 87, 46.0%) and liver-only recurrence (n = 28, 14.8%) generally occurred earlier and resulted in significantly worse OS when compared to local-only (n = 52, 27.5%) or lung-only recurrence (n = 18, 9.5%). Microscopic perineural invasion, yN1-yN2 status and elevated pre-surgery CA 19-9 >100 U/mL were associated with both local-only and multiple-site/liver-only recurrence. R1-margin was associated with local-only recurrence (HR 2.03). yN1-yN2 status and microscopic perineural invasion were independent predictors for both poor RFS and OS, while yT3-yT4 tumor stage (HR 1.39) and poor tumor differentiation (HR 1.60) were only predictive of poor OS. Adjuvant therapy was independently associated with both prolonged RFS (HR 0.73; median 7.0 vs. 10.9 months) and OS (HR 0.69; median 15.4 vs. 22.7 months). ConclusionDespite neoadjuvant therapy leading to resection and relatively favorable pathologic tumor characteristics in BRPC/LAPC patients, more than 80% of patients experienced disease recurrence, 72.5% of which occurred at distant sites.

Safety and Efficacy of Hypofractionated Radiotherapy With Capecitabine in Elderly Patients With Urothelial Carcinoma.

Bladder cancer is commonly diagnosed in patients ineligible for radical cystectomy or chemoradiotherapy (chemo-RT) with cisplatin or fluorouracil with mitomycin. We assessed tolerability, efficacy, and toxicity of hypofractionated radiotherapy with capecitabine in this challenging population. Patients with high-grade urothelial bladder cancer ineligible for radical cystectomy or high-intensity chemo-RT underwent maximal transurethral resection of bladder tumor followed by capecitabine (median, 825 mg/m2 per day 2 times a day) and radiation (median, 55 Gy in 2.2 Gy per fraction). Patients underwent surveillance cystoscopy and imaging, and were evaluated for toxicity, freedom from local failure and freedom from distant metastasis, progression-free survival, and overall survival. Eleven patients (median age, 80 years) with localized disease (n= 7), locally advanced disease (n= 3), or local-only recurrence after cystectomy (n= 1) were treated. Four patients (35%) had an Eastern Cooperative Oncology Group performance status of 2; median Charlson comorbidity index was 5. There was 1 acute grade 3 genitourinary event (9%), 6 acute grade 3 hematologic events (55%) of lymphopenia, and no acute grade 4 or higher events or hospitalizations. Ten patients (91%) completed radiotherapy, while 4 patients (36%) temporarily discontinued capecitabine. The complete response rate in the bladder was 64%. Two patients (18%) experienced late grade 1/2 genitourinary toxicities, and 1 (9%) experienced a transient late grade 4 genitourinary toxicity. With a median follow-up of 16.6 months, overall survival, progression-free survival, freedom from local failure, and freedom from distant metastasis at 1 year were 82%, 55%, 100%, and 55%, respectively, and at 2 years were 61%, 41%, 80%, and 55%, respectively. Hypofractionated chemo-RT was well tolerated and was associated with a high rate of local control in this comorbid population, thus providing a treatment option for select bladder cancer patients.

Salvage Re-Irradiation for Recurrent High-Grade Glioma and Comparison to Bevacizumab Alone

High-grade gliomas (HGGs) are the most common lethal primary brain tumor in adults and almost always recur after initial treatment. Despite this, there is little evidence arguing superiority of a single treatment strategy at time of recurrence, with options including supportive care, re-resection, systemic therapy, or re-irradiation. While bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is now commonly used for recurrent HGG, there has been longstanding interest in re-irradiation for patients with local-only recurrence. The purpose of this study is to examine outcomes of patients with recurrent HGG treated with re-irradiation. This is a retrospective analysis of patients with recurrent HGG who received salvage re-irradiation at a major academic institution from 2010-2014, as well as those who received bevacizumab alone. Progression-free survival (PFS) and overall survival (OS) were calculated from date of re-irradiation completion, or date of bevacizumab initiation in the bevaciumab alone cohort. Cox proportional hazards modeling was used to examine factors associated with OS. Propensity score modeling was used to compare survival after re-irradiation vs. bevacizumab alone. Sixty-seven patients received re-irradiation for recurrence, and 177 patients received bevacizumab alone. Among the re-irradiation cohort, 51% received concurrent bevacizumab. Median time in the re-irradiation cohort from initial diagnosis to re-irradiation was 31.4 months. The most common re-irradiation dose/fractionation regimens were 6 Gy x 5 (36%), 3.5 Gy x 10 (21%), 2.67 Gy x 15 (15%), and 18-20 Gy x 1 (15%). No early or late toxicities > grade 2 were observed. Median PFS and OS after re-irradiation were 4.8 months 10.7 months, respectively. Number of progressions prior to re-irradiation (adjusted hazard ratio [AHR], 1.6; 95% CI, 1.1-2.3; P = .007), and recurrence in a new brain location (vs. local-only; AHR, 7.4; 95% CI, 2.4-23.1; P < .001) were associated with OS; dose/fractionation regimen was not. Compared to bevacizumab alone, patients who received re-irradiation had a non-significant increase in OS (HR, 0.80; 95% CI, 0.53-1.23; P = .31). Among patients with local-only recurrence, there was a trend towards longer median OS after re-irradiation compared to bevacizumab alone (12.4 vs. 8.0 months; P = .12). Re-irradiation for recurrent HGG appears safe and was associated with reasonable PFS and OS even as many patients received bevacizumab and had >2 prior progressions. Number of progressions prior to re-irradiation and recurrence location were associated with OS, while dose/fractionation regimen was not. While re-irradiation was not associated with OS benefit in propensity score adjusted analysis compared with bevacizumab alone, there was a trend towards OS benefit in patients with local-only recurrence.

Salvage external beam radiotherapy for locally recurrent prostate cancer after definitive brachytherapy

PurposePatients with locally recurrent prostate cancer after definitive prostate brachytherapy have few evidence-based salvage options. We evaluate the efficacy and treatment-related side-effects of salvage external-beam radiotherapy (EBRT) after definitive prostate brachytherapy (PBT). Methods and MaterialsEleven patients previously treated with definitive PBT and with biopsy-proven local-only recurrence received salvage reirradiation with EBRT. Genitourinary (GU) function was assessed with International Prostate Symptom Scores. Treatment-related toxicities were graded using CTCAE v 4.03. ResultsMedian follow-up was 26.5 months (range, 1–53.6 months); median age at EBRT salvage was 67 years (range, 61–81 years). Salvage EBRT included the whole pelvis in 8 patients. Two patients were treated with 3D-CRT; 9 underwent IMRT. Five patients (45%) received androgen deprivation therapy concurrent with salvage EBRT as part of long- or short-course hormone therapy. The median prostate dose was 70.2 Gy (range, 64.8–75.6 Gy). Actuarial 3-year overall and biochemical failure–free survival were 77% and 69%, respectively. Five patients (45%) had worsening GU symptoms, and 9 (82%) experienced a decline in erectile function. One patient experienced acute grade 2 GU toxicity. Four patients (36%) experienced late grade ≥2 GI/GU toxicities, including 2 who experienced grade 3 toxicities (rectourethral fistula/incontinence, bladder outlet obstruction). No grade 4/5 toxicities were noted. ConclusionsOur data suggest that salvage EBRT can provide similar disease control and treatment-related toxicity to more established salvage therapies. This approach warrants further investigation on a larger scale.