Patterns Of Recurrence In Patients Research Articles

Clinical Outcome in Patients With Early-Stage Small Cell Lung Cancer Treated With Surgery or Radiation in the Absence of Prophylactic Cranial Irradiation: A Single-Center Retrospective Study

As screening chest computed tomography for patients at high risk for cancer has become more widely accepted, increasing numbers of patients with early-stage small cell lung cancer (SCLC) are being diagnosed. Although surgery is an accepted option for patients with early-stage SCLC, for patients who decline or cannot undergo surgery, stereotactic body radiation treatment (SBRT) is an alternative. Although prophylactic cranial irradiation (PCI) improves survival in patients with limited-stage SCLC, PCI for early-stage SCLC (stage T1-T2) has not been explored. This study defines survival and recurrence patterns in patients with early-stage SCLC who were treated with surgery or SBRT in the absence of PCI. In this single-institution retrospective study, 14 patients diagnosed with early-stage SCLC (stage T1-T2) between July 2015 and May 2021 at a single tertiary care hospital were treated with SBRT or surgery with no PCI. Primary outcomes were locoregional cancer recurrence, distant recurrence, recurrence-free survival, and overall survival. The secondary outcome was development of brain metastasis. Analyses included Cox regression, Kaplan-Meier survival, and log-rank tests. A total of 14 patients (5 women and 9 men) were included in the study: 9 with stage T1 and 5 with stage T2 SCLC. Six patients (43%) received SBRT and 8 (57%) had surgical treatment. All patients except 1 received adjuvant chemotherapy. Median follow-up was 14.3 months (range, 2.4-64.4 months), and the median age at diagnosis was 71.5 years (range, 54-81 years). Cox regression and log-rank tests showed no significant differences in any outcomes between the surgery and SBRT groups, and no patients developed brain metastases during the study period. Data are lacking regarding the benefit of PCI in early-stage SCLC. Although the sample size in this study was too small to draw any conclusions, the findings add to the ongoing dialogue regarding the importance of PCI in this patient population. No difference was identified in survival and cancer recurrence in patients who received either surgery or SBRT in the absence of PCI.

Preoperative controlling nutritional status score predicts systemic disease recurrence in patients with resectable biliary tract cancer.

This study aimed to evaluate the association between the preoperative Controlling Nutritional Status (CONUT) score, survival outcomes, and recurrence pattern in patients with resectable biliary tract cancer (BTC). A total of 224 BTC patients (gallbladder, n=69; intrahepatic bile ducts, n=26; perihilar bile ducts, n=72; distal bile duct, n=57) who underwent surgery with curative intent were enrolled. The best cutoff point of the preoperative CONUT score in discriminating survival was determined using χ2 scores. The sites of recurrence were subclassified as locoregional or distant. Patients were subdivided into the CONUT-low (score ≤ 3, n=156) and the CONUT-high (score > 3; n=68) groups. In-hospital mortality occurred more frequently in the CONUT-high group than in the CONUT-low group (7.4% vs. 1.3%; p=0.028). A high preoperative CONUT score was independently associated with worse overall survival (hazard ratio [HR] 1.906, p=0.001), worse disease-specific survival (HR 1.840, p=0.006), and worse recurrence-free survival (HR 1.680, p=0.005). Recurrence developed in 110 (49.1%) patients. A high preoperative CONUT score was independently associated with a higher risk of distant recurrence (HR 2.245, p=0.001), but not locoregional recurrence. The incidences of distant recurrence at 5 years were 55.4% and 34.2% in the CONUT-high and CONUT-low groups, respectively (p=0.001). The preoperative CONUT score independently predicts survival outcomes and may serve as a surrogate marker of aggressive systemic disease recurrence in patients with resectable BTC.

Glasgow Prognostic Score Predicts Survival and Recurrence Pattern in Patients With Hepatocellular Carcinoma After Hepatectomy.

The prognostic significance of the Glasgow Prognostic Score (GPS) on outcomes of liver resection for hepatocellular carcinoma (HCC) remains unclear; the aim of the study was to assess its significance. A total of 480 patients with HCC who underwent liver resection with curative intent at the Yokohama City University Hospital and Medical Center were enrolled in the study. Patients were classified into three groups: GPS-0, C-reactive protein (CRP) ≤1.0 mg/dl serum albumin ≥3.5 g/dl; GPS-1, CRP >1.0 mg/dl or serum albumin <3.5 g/dl; and GPS-2, CRP >1.0 mg/dl, serum albumin <3.5 g/dl. Prognostic factors for overall survival (OS) and disease-free survival (DFS) were analyzed retrospectively. The recurrence pattern was also investigated using GPS. Of the 480 patients, 382 (79.6%), 81 (16.9%), and 17 (3.5%) were assigned to GPS-0, GPS-1, and GPS-2, respectively. Elevated GPS, indocyanine green retention rate at 15 min, and protein induced by vitamin K antagonist-II (PIVKA-II) were significantly associated with a poor OS. Elevated GPS, alpha-fetoprotein, and PIVKA-II were significantly associated with a poor DFS by multivariate analysis. The number of patients with liver-only recurrence in GPS-0, GPS-1, and GPS-2 was 179 (86.1%), 40 (78.4%), and 9 (69.2%), respectively. The number of patients with four or more intrahepatic metastases in the GPS-0, GPS-1, and GPS-2 groups, was 33 (17.9%), 11 (27.5%), and 8 (88.9%), respectively. The number of patients with four or more intrahepatic metastases in the GPS-2 group was significantly higher (p<0.001). Preoperative GPS is a useful predictor of OS and recurrence pattern after liver resection with a curative intent for HCC.

Predictive factors for nodal recurrence in differentiated thyroid cancers

IntroductionDifferentiated thyroid carcinoma usually has a good prognosis. Primary treatment is surgery, followed by radioactive iodine ablation based on risk stratification. The incidence of local and distant recurrence is 30%. Recurrence can be managed surgically or with multiple cycles of radioactive iodine ablation. There are multiple risk factors for structural disease recurrence proposed by the American Thyroid Association. In this study, we attempted to study the risk factors of structural recurrence in differentiated carcinoma thyroid and the pattern of recurrence in patients with node negative thyroid cancer who underwent total thyroidectomy. MethodologyThis study selected a retrospective cohort of 1498 patients with differentiated thyroid cancer: out of these, 137 patients who presented after thyroidectomy with cervical nodal recurrence from January 2017 to December 2020 were included. The risk factors for central and lateral lymph node metastasis were analysed by univariate and multivariate analyses, including age, gender, T-stage, extrathyroidal extension, multifocality and high-risk variants. In addition, the presence of TERT/BRAF mutations was studied as a risk factor for central and lateral nodal recurrence. ResultsOut of 1498 patients, 137 who fit the inclusion criteria were analysed. Majority were female (73%); mean age was 43.1 years. Lateral compartment neck nodal recurrence was more common (84%), while isolated central compartment nodal recurrence occurred only in 16%. Most recurrences were seen in the first 1 year (23.3%) or after 10 years post-total thyroidectomy (35.7%). On univariate variate analysis, multifocality, extrathyroidal extension and high-risk variants stage were significant factors for nodal recurrence. However, on multivariate analysis for lateral compartment recurrence, multifocality, extrathyroidal extension and age were found to be significant. On multivariate analysis, multifocality, extrathyroidal extension and presence of high-risk variants were significant predictors of central compartment nodal metastasis. ROC curve analysis showed AUC for ETE (AUC-0.795), multifocality (AUC-0.860), presence of high-risk variants (AUC-0.727) and T-stage (AUC-0.771) as sensitive predictive factors for central compartment. 69 percent patients with very early recurrences (<6 month) had TERT/BRAF V600 E mutations. ConclusionIn our study, we have noted extrathyroidal extension and multifocality as significant risk factors for nodal recurrence. BRAF and TERT mutations are associated with aggressive clinical course and early recurrences. There is limited role of prophylactic central compartment node dissection.

Review for N2 Sub-staging in Non-small Cell Lung Cancer

Patients with N2 non-small cell lung cancer (NSCLC) were heterogeneous groups and required further stratification. The International Society for the Study of Lung Cancer (IASLC) divided N2 into three sub-stages: N2 at a single station without N1 involvement (N2a1), N2 at a single station with N1 involvement (N2a2), and N2 at multiple stations (N2b). These new descriptors significantly distinguished the overall survival (OS), disease-free survival (DFS), and recurrence pattern of patients with different N2 sub-stages. The OS and DFS of N2a1 were not sufficiently distinguished from N1 at multiple stations (N1b). The OS and DFS of N2a2 were intermediate between those of N2a1 and N2b. Current evidence did not support the further subdivision of the N2b. The main recurrence pattern of N2a1, N2a2 and N2b were distant metastasis, and the risks of distant metastasis increased successively. N2a1 patients were at low risk of locoregional recurrence, which could not be reduced by postoperative radiotherapy (PORT). N2a2 and N2b patients had a similar higher risk of locoregional recurrence, which could be reduced to a similar level of N2a1 patients by PORT. .

Feasibility of clinical target volume reduction for glioblastoma treated with standard chemoradiation based on patterns of failure analysis

PurposeTo analyze recurrence patterns in patients with glioblastoma (GBM) after standard chemoradiation according to different target volume delineation strategies. Methods and materialsTwo hundred seven patients with GBM who recurred after standard chemoradiation were evaluated. According to ESTRO target volume delineation guideline, the CTV was generated by adding a 2-cm margin to the GTV, defined as the resection cavity plus residual tumor. Patterns of failure were analyzed using dose-volume histogram. Recurrent lesions were defined as in-field, marginal, or distant if > 80 %, 20–80 %, or < 20 % of the intersecting volume was included in the 95 % isodose line.For each patient, a theoretical plan consisting of reduced 1-cm GTV-to-CTV margin was created to compare patterns of failure and radiation doses to normal brain. ResultsMedian overall survival and progression-free survival times were 15.3 months and 7.8 months, respectively, from the date of surgery. Recurrences were in-field in 180, marginal in 5, and distant in 22 patients. According to MGMT promoter methylation, distant recurrences occurred in 18.6 % of methylated and 6 % of unmethylated tumors (p = 0.0046). Following replanning with 1-cm reduced margin, dosimetric analysis showed similar patterns of failure. Recurrences were in-field, marginal, and distant in 177, 3, and 27 plans, respectively, although radiation doses to the healthy brain and hippocampi were significantly lower compared with standard target delineation (p = 0.0001). ConclusionCurrent provide the rationale for evaluating GTV-to-CTV margin reduction in future clinical trials with the aim of limiting the cognitive sequelae of GBM irradiation while maintaining survival benefits of standard chemoradiation.

HPB P67 Patterns of recurrence after pancreatoduodenectomy for pancreatic cancer and the effect of palliative chemotherapy on survival

Abstract Background Pancreatoduodenectomy (PD) is recommended in fit patients with suspected early pancreatic ductal adenocarcinoma (PDAC) affecting the pancreatic head. Unfortunately, recurrence rates are high and only a minority achieve long-term survival. This study aimed to study the patterns of recurrence in patients who undergo PD for PDAC and investigate the impact of palliative chemotherapy on survival. Methods Data was extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective cohort study of outcomes following PD performed for pancreatic head malignancy (29 centres in 8 countries, n=1,484). Patients with PDAC who developed recurrence within five years of their operation were identified. The site of recurrence and details of palliative chemotherapy (if any) was recorded for each patient. Overall survival (OS) and time from recurrence to time of death was compared between those that received palliative chemotherapy and those that did not using the Mann-Whitney U test. Results In total, 885 patients (59.4%) had PDAC. Excluding the 37 patients who died within 90-days, 583 (68.8%) developed recurrent disease within five years (on imaging). The median number of months from time of surgery to time of recurrence was ten months (range: 0–58). Of those with recurrence, 30.4% had local recurrence only, 28.4% had local and distal recurrence, and 41.7% had distant recurrence only. The most common sites of recurrence were the liver (40.7%), the superior mesenteric artery area (33.3%), locoregional lymph nodes (20.2%), the omentum/peritoneum (14.9%), the pancreatic anastomosis site (11.8%), the superior mesenteric vein/portal vein area (10.8%), and the coeliac trunk area (9.4%). Among those with recurrence, 46.1% received palliative chemotherapy. The median number of cycles was four (range: 1–12). Just 41.2% of patients completed their planned course; 28.0% stopped their treatment due to disease progression and 17.4% stopped their treatment due to toxicity. Patients who received palliative chemotherapy had similar median OS to those who did not (both 18 months, p=0.6), however, time from recurrence to time of death was significantly longer in the former (9 vs 3 months, p&amp;lt;0.0001). Conclusions In our multicentre study, over two thirds of PD patients with PDAC developed disease recurrence within five-years of their operation. Just under half of these received palliative chemotherapy. Time from recurrence to time of death was significantly longer in those who did receive palliative chemotherapy.

Recurrence Patterns for Regionally Metastatic Melanoma Treated in the Era of Adjuvant Therapy: A Systematic Review and Meta-Analysis.

The purpose of this systematic review was to examine the timing and patterns of recurrence for patients with regionally metastatic melanoma on the basis of nodal management and receipt of adjuvant therapy. We identified randomized controlled trials and non-randomized studies published between 2010 and 2020 that reported timing and/or patterns of recurrence. We evaluated recurrence-free survival (RFS), location of recurrence, and surveillance strategy on the basis of receipt of adjuvant systemic therapy and nodal management with observation versus completion dissection. We compared differences in patterns of recurrence across studies using RevMan. RFS was evaluated graphically using point estimates and confidence intervals. Among the 19 publications, there was wide variation in study populations, imaging surveillance regimens, and format of recurrence reporting. Patterns of disease recurrence did not differ between adjuvant and placebo/observation groups. A total of 11 studies reported RFS at variable time intervals, which ranged in adjuvant therapy groups (38-88% at 1 year, 29-67% at 2 years, 33-58% at 3 years, and 34-53% at 5 years) and placebo/observation groups (47-63% at 1 year, 39-47% at 2 years, 33-68% at 3 years, and 57% at 5 years). Anti-PD-1 immune therapy and BRAF/MEK inhibitor therapy were superior to placebo at year 1. We found that adjuvant treatment improved RFS but did not alter the patterns of disease recurrence compared with patients managed without adjuvant systemic treatment. Future studies should separately report sites of disease recurrence on the basis of specific adjuvant systemic treatment and surveillance practices to better advise patients about their patterns and risk of recurrence.

Recurrence patterns in bladder cancer patients with no residual disease (pT0N0) at radical cystectomy: A 20-year experience

ObjectiveTo examine the oncological outcomes and recurrence patterns in patients with no residual disease at the time of radical cystectomy (RC). MethodsA retrospective review of our IRB-approved bladder cancer database identified patients who underwent RC between 2000 and 2019 and were found to have no residual disease (pT0N0), either following neoadjuvant chemotherapy (NAC) or transurethral resection (TURBT) alone. The primary outcome was recurrence-free survival (RFS). Regression models assessed factors influencing recurrence, and a detailed description of recurrence patterns was compiled. ResultsFrom a total of 2222 patients, 234 (10.5%) were included with a median age of 67 years. NAC was used in 89 (38%) patients and 145 (62%) cases were rendered pT0 following TURBT alone. At a median follow-up of 44 months, there were 16 (6.8%) recurrences, 10 (63%) of which occurred in the ypT0 group. None of the patients with clinical Ta/Tis disease had a recurrence after RC. The median time to recurrence was 9 months. Ninety-one percent (10/11) of recurrences in the ypT0 group were within 2 years of cystectomy, while half of the recurrences in the pT0 group occurred after 2 years. Patients with ypT0 had worse 2- and 5-year RFS compared to the pT0 group (85% and 84% vs. 99% and 95%, respectively; P = 0.003). Variant histology was noted in 49 (21%) patients; the recurrence rate was higher in this subgroup compared to those with pure urothelial carcinoma (12.2% vs. 5.4%, P = 0.02). Lung metastasis and involvement of distant organs, while rare, were noted at similar rates in both groups. ConclusionPatients with pT0N0 pathology at the time of cystectomy should prudently undergo long-term surveillance as recurrence and metastasis can still develop up to 4 years after surgery. Patients achieving ypT0 after NAC exhibit worse prognosis and shorter times to recurrence, closer follow-up may be considered.

RAS Pathway Alterations in Pediatric AML Patients

RAS pathway alterations are highly prevalent in hematologic malignancies1,2, often involving gain of function KRAS, NRAS or HRAS mutations and have been linked to tumorigenesis and associated with poorer prognosis in different cancer entities3-5. In adult myeloid leukemia, RAS mutations are one of the most common mutations, yet show no clear prognostic value6. In a study of the Japanese pediatric AML cohort, NRAS mutations were associated with a favorable outcome, the effect of KRAS mutations could not be analyzed due to the limited patient size7. Here we report the outcome of 372 pediatric AML patients of the German AML-BFM study between 2016 and 2021 that were characterized by morphology, multicolor flow cytometry, classical cytogenetics and mutation analysis via panel sequencing. In total, 27% (n=102) of the patients showed a RAS pathway alteration, involving n=32 patients (9%) with a KRAS mutation and n=75 (20%) with a NRAS mutation. Notably, no HRAS mutation was detected in our cohort. Age distribution did not differ between the groups (Fig. A). Interestingly, the KRAS cohort consisted mostly of male patients (72%, p=0,0087), while the overall cohort was balanced (48,7% male patients). NRAS and KRAS mutations were strong predictors of therapy response and early death. Only 1/75 (1,3%) of all patients harboring a NRAS mutations showed poor response to induction therapy compared to patients without a NRAS mutation (10,10%, p=0,01). KRAS mutations on the opposite were strongly associated with non-response (21,9%; p<0,01) and subsequent early deaths (n=6/32; p=0,001) compared to patients without KRAS mutations (3,2%). Of note, only 1/75 (1,3%) of patients with NRAS mutation and 17/372 (4,6%) of all AML patients suffered early deaths. Risk stratification taking into account re-stratification after poor therapy response showed a significant higher proportion of high-risk patients in the KRAS-mutated cohort (43,8 %) compared to 20% in the patients with NRAS mutations (p=0,0022). KRAS mutations correlated with KMT2A-MLLT1 (15,6%; p=0,01) translocations, which were significantly rarer in patients without KRAS mutations (3,5%). NRAS mutations occurred frequently with CBFA2T3-RUNX1 (14,7%; p=0,0002) and CBFB-MYH11 translocations (12%; p=0,0068%) as well as KIT mutations (12%; p=0,026). Existence of RAS mutations showed overall no significant impact on event-free survival (EFS=69,6% ±4,8%) and overall survival (OS=82,8% ±4,2%) compared to RAS wildtype (EFS=66,4% ±3,1% ; OS=76,5% ±2,9%) (Fig. B). Multivariate analysis comparing outcome for several subgroups also showed no significant differences. In summary, we show worse therapy response and increased early death rates in patients with KRAS mutations, while NRAS mutations are associated with better therapy response. These findings warrant further analyses and longer follow-up on the cohort to determine long-term significances of RAS pathway alterations in pediatric AML patients. 1.de Luca, A., Maiello, M. R., D'Alessio, A., Pergameno, M. & Normanno, N. The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin Ther Targets16 Suppl 2, (2012). 2.Hobbs, G. A., Der, C. J. & Rossman, K. L. RAS isoforms and mutations in cancer at a glance. Journal of Cell Science129, 1287-1292 (2016). 3.Hsu, H. C. et al. Mutations of KRAS/NRAS/BRAF predict cetuximab resistance in metastatic colorectal cancer patients. Oncotarget7, 22257 (2016). 4.Vauthey, J., Zimmitti, G., Kopetz, S., ... J. S.-A. of & 2013, undefined. RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases. ncbi.nlm.nih.gov. 5.Dinu, D. et al. Prognostic significance of KRAS gene mutations in colorectal cancer - preliminary study. Journal of Medicine and Life7, 581 (2014). 6.Neubauer, A. et al. Patients With Acute Myeloid Leukemia and RAS Mutations Benefit Most From Postremission High-Dose Cytarabine: A Cancer and Leukemia Group B Study. Journal of Clinical Oncology26, 4603 (2008). 7.Kaburagi, T. et al. Clinical significance of RAS pathway alterations in pediatric acute myeloid leukemia. Haematologica107, 583-592 (2022). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

SURG-25. PATTERNS OF RECURRENCES ACCORDING TO THE EXTENT OF RESECTION IN PARIETNS WITH GLIOBLASTOMA, IDH-WILDTYPE: A RETROSPECTIVE STUDY

Abstract OBJECTIVE In glioblastoma (GBM) patients, controlling the microenvironment around the tumor using various treatment modalities, including surgical intervention, is essential in determining the outcome of treatment. This study was conducted to elucidate whether recurrence patterns differ according to the extent of resection (EOR) and whether this difference affects prognosis. METHODS This single-center study included 358 eligible patients with histologically confirmed isocitrate dehydrogenase (IDH)-wild-type GBM from November 1, 2005, to December 31, 2018. Patients were assigned to one of three separate groups according to EOR: supratotal resection (SupTR), gross-total resection (GTR), and subtotal resection (STR) groups. The patterns of recurrence were classified as local, marginal, and distant based on the range of radiation. The relationship between EOR and recurrence pattern was statistically analyzed. RESULTS Observed tumor recurrence rates for each group were as follows: SupTR group, 63.4%; GTR group, 75.3%; and STR group, 80.5% (p = 0.072). Statistically significant differences in patterns of recurrences among groups were observed with respect to local recurrence (SupTR, 57.7%; GTR, 76.0%; STR, 82.8%; p = 0.036) and distant recurrence (SupTR, 50.0%; GTR, 30.1%; STR, 23.2%; p = 0.028). Marginal recurrence showed no statistical difference between groups. Both overall survival and progression-free survival were significantly increased in the SupTR group compared with the STR and GTR groups (p &amp;lt; 0.0001). CONCLUSIONS In this study, the authors investigated the association between EOR and patterns of recurrence in patients with IDH-wild-type GBM. The findings not only show that recurrence patterns differ according to EOR but also provide clinical evidence supporting the hypothesized mechanism by which distant recurrence occurs.

PN3b as an independent risk factor for poor prognosis and peritoneal recurrence in Borrmann type IV gastric cancer: A retrospective cohort study

The clinicopathological features and surgical treatment strategies of Borrmann type IV gastric cancer (GC) remain controversial. Peritoneal metastasis is the most common recurrence pattern in patients with Borrmann type IV GC. Among 2026 gastric cancer between January 2009 and August 2019, 159 cases of Borrmann type IV GC were included in this study (7.8%). We retrospectively analyzed the clinicopathological characteristics and prognosis of these patients. Univariate and multivariate Cox proportional hazards were applied to identify independent prognostic factors. Predictors related to peritoneal metastasis of type IV GC were analyzed by multivariate Cox regression analysis. Borrmann type IV gastric cancer was associated with more advanced clinicopathological features at diagnosis than the other Borrmann type GC. Of the 159 patients with Borrmann type IV GC, the median OS was 23 months. The number of patients with peritoneal metastasis was 43, accounted for 27.0% of all the patients and 87.8% of the patients with distant metastasis. Multivariate analyses revealed lymph node metastasis to be independent prognostic factor for survival in Borrmann type IV GC patients. pN3b and tumor size > 50 mm showed to be risk factors for peritoneal metastasis. Borrmann type IV GC is an important independent prognostic factor. pN3b is an independent prognostic factor and a predictor of peritoneal metastasis in patients with Borrmann type IV GC.

CA19.9 Response and Tumor Size Predict Recurrence Following Post-neoadjuvant Pancreatectomy in Initially Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma

BackgroundData on recurrence after post-neoadjuvant pancreatectomy are scant. This study investigated the incidence and pattern of recurrence in patients with initially resectable and borderline resectable pancreatic ductal adenocarcinoma who received post-neoadjuvant pancreatectomy. Furthermore, preoperative predictors of recurrence-free survival (RFS) and their interactions were determined.Patients and MethodsPatients undergoing post-neoadjuvant pancreatectomy at two academic facilities between 2013 and 2017 were analyzed using standard statistics. The possible interplay between preoperative parameters was scrutinized including interaction terms in multivariable Cox models.ResultsAmong 315 included patients, 152 (48.3%) were anatomically resectable. The median RFS was 15.7 months, with 1- and 3-year recurrence rates of 41.9% and 74.2%, respectively. Distant recurrence occurred in 83.3% of patients, with lung-only patterns exhibiting the most favorable prognostic outlook. Normal posttreatment CA19.9, ΔCA19.9 (both in patients with normal and elevated baseline levels), and posttreatment tumor size were associated with RFS. Critical thresholds for ΔCA19.9 and tumor size were set at 50% and 20 mm, respectively. Interaction between ΔCA19.9 and posttreatment CA19.9 suggested a significant risk reduction in patients with elevated values when ΔCA19.9 exceeded 50%. Moreover, posttreatment tumor size interacted with posttreatment CA19.9 and ΔCA19.9, suggesting an increased risk in the instance of elevated posttreatment CA19.9 values and a protective effect associated with CA19.9 response in patients with tumor size >20 mm.ConclusionRecurrence following post-neoadjuvant pancreatectomy is common. Preoperative tumor size <20 mm, normal posttreatment CA19.9 and ΔCA19.9 > 50% were associated with longer RFS. These variables should not be taken in isolation, as their interaction significantly modulates the recurrence risk.

Folate receptor-positive circulating tumor cells predict survival and recurrence patterns in patients undergoing resection for pancreatic cancer.

ObjectiveTo evaluate the prognostic impact of folate receptor (FR)-positive circulating tumor cells (FR+ CTCs) for patients with pancreatic cancer (PC).BackgroundRisk stratification before surgery for PC patients remains challenging as there are no reliable prognostic markers currently. FR+ CTCs, detected by ligand-targeted polymerase chain reaction (LT-PCR), have shown excellent diagnostic value for PC in our previous study and prognostic value in a variety of cancer types.MethodsPeripheral blood samples from 44 consecutive patients diagnosed with PC were analyzed for FR+ CTCs. 25 patients underwent tumor resection and were assigned to the surgical group. 19 patients failed to undergo radical resection because of local advance or distant metastasis and were assigned to the non-surgical group. The impact of CTCs on relapse and survival were explored.ResultsFor the prognostic stratification, the optimal cut-off value of CTCs analyzed by receiver operating characteristic (ROC) curve was 14.49 folate units (FU)/3 ml. High CTC levels (> 14.49 FU/3 ml) were detected in 52.0% (13/25) of the patients in the surgical group and 63.2% (12/19) in the non-surgical group. In the surgical group, median disease-free survival (DFS) for patients with high CTC levels versus low CTC levels (< 14.49 FU/3 ml) was 8.0 versus 26.0 months (P = 0.008). In multivariable analysis, CTCs were an independent risk factor for DFS (HR: 4.589, P = 0.012). Concerning the recurrence patterns, patients with high CTC levels showed a significantly frequent rate of distant and early recurrence (P = 0.017 and P = 0.011). CTC levels remained an independent predictor for both distant (OR: 8.375, P = 0.014) and early recurrence (OR: 8.412, P = 0.013) confirmed by multivariable logistic regression. However, CTCs did not predict survival in the non-surgical group (P = 0.220).ConclusionFR+ CTCs in resected PC patients could predict impaired survival and recurrence patterns after surgery. Preoperative CTC levels detected by LT-PCR may help guide treatment strategies and further studies in a larger cohort are warranted.

Clinical impact of surgical treatment for the spontaneously ruptured resectable hepatocellular carcinoma: A single institution experience

Spontaneously ruptured hepatocellular carcinoma (srHCC) is a fatal complication of hepatocellular carcinoma (HCC). In addition, emergency treatment is frequently fraught with difficulties. This study aimed to investigate the prognosis and recurrence pattern in patients undergoing hepatectomy for the srHCC. This retrospective study included 11 patients with srHCC treated using either emergency hepatectomy or emergency transarterial embolization (TAE) followed by staged hepatectomy between January 2015 and December 2019. The patients visited the emergency room because of a sudden rupture of HCC without being diagnosed with HCC. We analyzed the prognosis, recurrence rate, and survival in these patients after hepatectomy. Four of the 11 patients in this study were classified as Child–Pugh class A and 7 as Child–Pugh class B. Nine patients visited for sudden onset of abdominal pain, and 2 for sudden onset of shock. The median hemoglobin level at the time of the visit was 11.5 g/dL (interquartile range: 9.8–12.7). Five patients underwent one-stage hepatectomy and 6 underwent emergency TAE hemostasis followed by staged hepatectomy. Median overall survival and recurrence-free survivals were 23 and 15 months, respectively. Recurrence occurred in 7 patients (4 in the one-stage group and 3 in the staged group). Among patients with recurrence, 6 had intrahepatic recurrence and 3 peritoneal metastases. Patients with srHCC who undergo staged hepatectomy can achieve a relatively good prognosis. The most common sites of recurrence after hepatectomy are intrahepatic and peritoneal. Peritoneal metastases are more likely to occur after one-stage hepatectomy.

Effect of p16 Status on Survival Outcomes in Sinonasal Squamous Cell Carcinoma.

Evaluate the effect of p16 status on disease-free survival (DFS) and overall survival (OS) in patients with sinonasal squamous cell carcinoma (SCC) undergoing treatment with curative intent; and to assess how p16 status may affect patterns of recurrence. Retrospective cohort study. Tertiary medical center. Patients with sinonasal SCC treated with curative intent from 2012 to 2018 were identified. Independent variable of interest was p16 status, which was assessed using immunohistochemistry (IHC) with a 70% staining cutoff for positivity. Kaplan Meier survival curve was plotted to assess correlation between p16 status and DFS and OS. Association between recurrence patterns and p16 status was conducted using chi square and fisher's exact tests. Multivariable Cox proportional hazard analysis was conducted to assess association between independent variables and DFS. Fifty patients with sinonasal SCC met inclusion criteria. Patients were p16 positive in 28/50 (56%) of cases. Kaplan Meier survival curve revealed no statistically significant association between p16 status and DFS or OS survival (P = .780, P = .474). There was no difference in recurrence patterns in patients with p16 positive versus negative tumors. p16 status did not have prognostic value on DFS and OS in our cohort of patients with sinonasal SCC undergoing treatment with curative intent. There was no difference in recurrence patterns between the 2 populations. Based on the results of this study, p16 status should not impact counseling of patients as it relates to their prognosis from SNM.

Patterns of recurrence according to the extent of resection in patients with IDH-wild-type glioblastoma: a retrospective study.

In glioblastoma (GBM) patients, controlling the microenvironment around the tumor using various treatment modalities, including surgical intervention, is essential in determining the outcome of treatment. This study was conducted to elucidate whether recurrence patterns differ according to the extent of resection (EOR) and whether this difference affects prognosis. This single-center study included 358 eligible patients with histologically confirmed isocitrate dehydrogenase (IDH)-wild-type GBM from November 1, 2005, to December 31, 2018. Patients were assigned to one of three separate groups according to EOR: supratotal resection (SupTR), gross-total resection (GTR), and subtotal resection (STR) groups. The patterns of recurrence were classified as local, marginal, and distant based on the range of radiation. The relationship between EOR and recurrence pattern was statistically analyzed. Observed tumor recurrence rates for each group were as follows: SupTR group, 63.4%; GTR group, 75.3%; and STR group, 80.5% (p = 0.072). Statistically significant differences in patterns of recurrences among groups were observed with respect to local recurrence (SupTR, 57.7%; GTR, 76.0%; STR, 82.8%; p = 0.036) and distant recurrence (SupTR, 50.0%; GTR, 30.1%; STR, 23.2%; p = 0.028). Marginal recurrence showed no statistical difference between groups. Both overall survival and progression-free survival were significantly increased in the SupTR group compared with the STR and GTR groups (p < 0.0001). In this study, the authors investigated the association between EOR and patterns of recurrence in patients with IDH-wild-type GBM. The findings not only show that recurrence patterns differ according to EOR but also provide clinical evidence supporting the hypothesized mechanism by which distant recurrence occurs.

Prognosis and recurrence patterns in patients with early stage lung cancer: a multi-state model approach

BackgroundWe aimed to assess whether recurrence patterns affect survival and to use a multi-state model to predict the prognosis of early stage non-small cell lung cancer in patients who underwent surgical resection.MethodsPatients with early stage non-small cell lung cancer who underwent surgical resection at two tertiary medical centers between 2010 and 2015 were retrospectively analyzed. A multi-state model was employed with one initial state (surgery), two intermediate states (locoregional recurrence, distant metastasis), and one absorbing state (death), comprising five transitions: surgery to locoregional recurrence, surgery to distant metastasis, surgery to death without recurrence, locoregional recurrence to death, and distant metastasis to death. Cox proportional hazards models stratified for these transitions were performed with the risk factors; transition probabilities for each patient were predicted.ResultsA total of 949 patients were identified [median age: 67 years, male: 614 (64.6%)]. Recurrence occurred in 194 (20.4%) patients (locoregional recurrence: 7.3%, distant metastasis: 13.1%). Hazard ratios for distant metastasis after surgery were higher for older age (hazard ratio: 1.03, 95% confidence interval: 1.01–1.06) and adenocarcinoma (hazard ratio: 1.67, 95% confidence interval: 1.06–2.61). Lower lobe location exhibited a higher hazard ratio for death after surgery without recurrence (hazard ratio: 1.59, 95% confidence interval: 1.00–2.53). Stage IIB lung cancer showed a higher probability of transition to distant metastasis after surgery than other stages. Cumulative transition hazards rapidly increased in both recurrence patterns until approximately two years after surgery (locoregional recurrence: 0.052; distant metastasis: 0.104). Patients with distant metastasis were more likely to die within 5 years of surgery than those with locoregional recurrence (6.8% and 2.6%, respectively).ConclusionsWith the multi-state model, risk factors and post-relapse survival probabilities differed between locoregional recurrence and distant metastasis. These findings may enable clinicians to establish personalized follow-up strategies for patients undergoing curative resection for early stage non-small cell lung cancer.

A Prospective Observational Study of the Recurrence Characteristics of Hunner Lesion After Repeated Transurethral Ablation in Patients With Interstitial Cystitis/Bladder Pain Syndrome.

PurposeThe aim of this study was to investigate the rate and pattern of recurrence for patients with Hunner lesion (HL) type interstitial cystitis/bladder pain syndrome (IC/BPS) after transurethral ablation.MethodsThis prospective study included 210 patients with HL type IC/BPS. The primary outcomes were the recurrence rate according to 3 patterns of recurrence: pattern A (according to the relationship with the previous surgical site), pattern B (according to the bladder zone), and pattern C (according to the number of lesions). The secondary outcomes were recurrencefree time after treatment according to pattern A and pattern C.ResultsThe pattern A recurrence rate was 50.8% in the same site (A1), 6.7% at a new site (A2), and 42.5% at mixed sites (A3). The pattern B recurrence rate was 10.5% for the anterior wall, 59.0% for the posterior wall, 69.5% for the lateral wall, and 69.0% for the dome area. Multiple lesions recurred as multiple lesions in 75.8% of cases. The pattern C recurrence rate was 10.8% for C1 (single → single), 6.7% for C2 (single → multiple), 6.7% for C3 (multiple → single), and 75.8% for C4 (multiple → multiple). The recurrence-free time in pattern A was 13 months for A1, 12.5 months for A2, and 8 months for A3, with a significant difference between A1 and A3 (P=0.008). There was no significant difference in recurrence-free time in pattern C, either with single or multiple HLs.ConclusionsThe distinct recurrence characteristics of HLs was not predictable despite repeated ablations. Complete remission should not be expected because the whole bladder was to have the potential to develop the HLs even after repeated transurethral ablation.

Clinical prediction model of pathological response following neoadjuvant chemoradiotherapy for rectal cancer

Patients with pathologic complete response (pCR) achievement can consider local excision or “watch and wait” strategy instead of a radical surgery. This study analyzed the predictive factors of pCR in rectal cancer patients who underwent radical operation after neoadjuvant chemoradiotherapy (nCRT). This study also analyzed the recurrence patterns in patients who achieved pCR and the oncologic outcomes and prognostic factors by ypStage. Between 2000 and 2013, 1,089 consecutive rectal cancer patients who underwent radical resection after nCRT were analyzed. These patients were classified into two groups according to pCR. The clinicopathologic and oncologic outcomes were analyzed and compared between the two groups. Multivariate analysis was conducted on factors related to pCR. The proportion of patients achieving pCR was 18.2% (n = 198). The pCR group demonstrated earlier clinical T and N stages, smaller tumor size, better differentiation, and a lower percentage of circumferential resection margin (CRM) involvement than did the non-pCR group. The prognostic factors associated with poorer disease-free survival were high preoperative carcinoembryonic antigen levels, non-pCR, poor histology, lymphatic/perineural invasion, and involvement of CRM. Multivariate analysis revealed that clinical node negativity, tumor size < 4 cm, and well differentiation were significant independent clinical predictors for achieving pCR. Patients with pCR displayed better long-term outcomes than those with non-pCR. The pCR-prediction model, based on predictive factors, is potentially useful for prognosis and for prescribing a treatment strategy in patients with advanced rectal cancer who need nCRT.