Efficacy and safety of systemic induction therapy in initially unresectable locally advanced intrahepatic and perihilar cholangiocarcinoma: A systematic review

BackgroundAccording to international guidelines, induction therapy may be considered in selected patients with initially unresectable locally advanced cholangiocarcinoma. The criteria for (un)resectability in cholangiocarcinoma varies between studies and no consensus-based agreement is available about these criteria. By performing a systematic literature review, we aimed to investigate the efficacy and safety of systemic induction therapy in initially unresectable locally advanced perihilar (pCCA) and intrahepatic cholangiocarcinoma (iCCA) and summarize resectability criteria used across studies.MethodsA literature search was performed in PubMed, EMBASE, Web of Science and Cochrane library to identify studies on systemic induction therapy in locally advanced pCCA and/or iCCA. The primary outcome was resection rate (RR) after induction therapy and secondary outcomes were overall survival (OS) and objective response rate (ORR).ResultsTen studies with a total of 1167 patients met the inclusion criteria and were included in this review. Among these patients, 334 (28.6%) were treated with systemic induction therapy. Across the studies, different types of chemotherapy regimens were administered (e.g., gemcitabine (based) chemotherapy and 5-FU (based) chemotherapy). Only six studies provided sufficient data and were used to analyze pooled (radical) resection rates. After induction therapy, 94 patients (39.2%) underwent a resection, of which R0 resections (22.9%). Pooled data on OS showed, better OS for chemotherapy plus resection versus chemotherapy only (pooled HR = 0.31, 95% CI = 0.19–0.50; P value < 0.0001).ConclusionAdequately selected patients with locally advanced pCCA or iCCA may benefit from induction therapy followed by surgical resection. Prospective randomized controlled trials are warranted.     

The prognostic role of lymphovascular invasion and lymph node metastasis in perihilar and intrahepatic cholangiocarcinoma

IntroductionCholangiocellular carcinoma (CCA) is an aggressive malignancy with a dismal prognosis. Among curative treatment options for CCA, radical surgical resection with extrahepatic bile duct resection, hepatectomy and en-bloc lymphadenectomy are considered the mainstay of curative therapy. Here, we aimed to identify prognostic markers of clinical outcome in CCA-patients who underwent surgical resection in curative intent.Material and methodsBetween 2011 and 2016, 162 patients with CCA (perihilar CCA (pCCA): n = 91, intrahepatic CCA (iCCA): n = 71) underwent surgery in curative intent at our institution. Preoperative characteristics, perioperative data and oncological follow-up were obtained from a prospectively managed institutional database. The associations of overall- (OS) and disease-free-survival (DFS) with clinico-pathological characteristics were assessed using univariate and multivariable cox regression analyses.ResultsThe median OS and DFS were 38 and 36 months for pCCA and 25 and 13 months for iCCA, respectively. Lymphovascular invasion (LVI) and lymph node metastasis as well as surgical complications as assessed by the comprehensive complication index (CCI) and tumor grading were independently associated with OS for the pCCA (LVI; RR = 2.36, p = 0.028; CCI; RR = 1.04, p < 0.001) and iCCA cohorts (N-category; RR = 3.21, p = 0.040; tumor grading; RR = 3.75, p = 0.013; CCI, RR = 4.49, p = 0.010), respectively. No other clinical variable including R0-status and Bismuth classification was associated with OS.ConclusionMajor liver resections for CCA are feasible and safe in experienced high-volume centers. Lymph node metastasis and LVI are associated with adverse clinical outcome, supporting the role of systematic lymphadenectomy. The assessment of LVI may be useful in identifying high-risk patients for adjuvant treatment strategies.     

Outcomes of vascular resection associated with curative intent hepatectomy for intrahepatic cholangiocarcinoma

Background and aimsWe aimed to investigate the impact of vascular resection (VR) on postoperative outcomes and survival of patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC).MethodsA retrospective analysis of a multi-institutional series of 270 patients with resected ICC was carried out. Patients were divided into three groups: portal vein VR (PVR), inferior vena cava VR (CVR) and no VR (NVR). Univariate and multivariate analysis were applied to define the impact of VR on postoperative outcomes and survival.ResultsThirty-one patients (11.5%) underwent VR: 15 (5.6%) to PVR and 16 (5.9%) to CVR. R0 resection rates were 73.6% in NVR, 73.3% of PVR and 68.8% in CVR. The postoperative mortality rate was increased in VR groups: 2.5% in NVR, 6.7% in PVR and 12.5% in CVR. The 5-years overall survival (OS) rates progressively decreased from 38.4% in NVR, to 30.1% in CVR and to 22.2% in PVR, p = 0.030. However, multivariable analysis did not confirm an association between VR and prognosis. The following prognostic factors were identified: size ≥50 mm, patterns of distribution of hepatic nodules (single, satellites or multifocal), lymph-node metastases (N1) and R1 resections. In the VR group the 5-years OS rate in patients without lymph-node metastases undergoing R0 resection (VRR0N0) was 44.4%, while in N1 patients undergoing R1 resection was 20% (p < 0.001).ConclusionVascular resection (PVR and CVR) is associated with higher operative risk, but seems to be justified by the good survival results, especially in patients without other negative prognostic factors (R0N0 resections).     

Presence of low-grade IPMN at the pancreatic transection margin does not have prognostic significance after resection of IPMN-associated pancreatic adenocarcinoma

IntroductionResection margin status is a well-established prognosticator in pancreatic cancer. The prognostic impact of IPMN dysplasia at the pancreatic transection margin in IPMN-associated carcinoma (IPMN-Ca) remains unclear, hence institutional practices on additional resections vary.MethodsPatients undergoing partial pancreatectomy or attempted partial pancreatectomy converted to total pancreatectomy for IPMN-Ca between 04/2002 and 12/2018 were identified. Final pathology of the definitive pancreatic transection margin was identified. The association between the presence of IPMN dysplasia at the margin and overall survival (OS) was assessed.ResultsOf 302 patients with IPMN-Ca, 181 (59.9%) patients received partial pancreatoduodenectomy, 61 (20.2%) distal pancreatectomy, and 60 (19.9%) were converted to total pancreatectomy. Median OS was 98.6 months in R0 (≥1 mm), 39.3 months in R1 (<1 mm), and 22.0 months in R1(direct) resected patients, respectively (p < 0.0001). No IPMN dysplasia at the definitive margin was present in 103 (34.1%), low-grade in 131 (43.4%), and high-grade/R1 in 8 (2.6%) patients. Low-grade dysplasia or total pancreatectomy were not associated with shorter OS compared to dysplasia-free margin across the entire cohort. Sensitivity analyses confirmed a lack of prognostic relevance of low-grade IPMN dysplasia at the pancreatic margin in R0 resected IPMN-Ca and in R0 resected UICC stage IA/IB IPMN-Ca.ConclusionsLow-grade IPMN at the transection margin is not associated with shorter overall survival after partial pancreatectomy for IPMN-Ca. Additional resections for low-grade dysplasia, up to total pancreatectomy do not result in a survival benefit and should be omitted. Due to limited sample size, high-grade dysplasia could not be analyzed.     

Benefit of Metastasectomy in Renal Cell Carcinoma: A Propensity Score Analysis

IntroductionTo quantify the magnitude of benefit of metastasectomy as compared to medical treatment alone in patients with metastatic renal cell carcinoma (mRCC).Patients and MethodsWe therefore conducted a propensity score analysis of overall survival (OS) in 106 mRCC patients with metachronous metastasis, of whom 36 (34%) were treated with metastasectomy, and 70 (66%) with medical therapy alone.ResultsThe most frequent metastasectomy procedures were lung resections (n = 13) and craniotomies (n = 6). Median time-to-progression after metastasectomy was 0.7 years (25th-75th percentile: 0.3-2.7). After a median follow-up of 6.2 years and 63 deaths, 5-year OS estimates were 41% and 22% in the metastasectomy and medical therapy group, respectively (log-rank P = .00007; Hazard ratio (HR) = 0.38, 95%CI: 0.21-0.68). Patients undergoing metastasectomy had a significantly higher prevalence of favorable prognostic factors, such as fewer bilateral lung metastases and longer disease-free intervals between nephrectomy and metastasis diagnosis. After propensity score weighting for these differences and adjusting for immortal time bias, the favorable association between metastasectomy and OS became much weaker (HR = 0.62, 95%CI: 0.39-1.00, P = .050). Propensity-score-weighted 5-year OS estimates were 24% and 20% in the metastasectomy and medical therapy group, respectively (log-rank P = .001). In exploratory analyses, the benefit of metastasectomy was confined to patients who achieved complete resection of all known metastases.ConclusionWithin the limitations of an observational study, these findings support the concept of metastasectomy being associated with an OS benefit in mRCC patients. Metastasectomies not achieving complete resection of all known lesions are likely without OS benefit.     

Outcomes following synchronous liver resection,cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases: A bi-institutional study

PurposeSynchronous liver resection, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal liver (CRLM) and peritoneal metastases (CRPM) has traditionally been contraindicated. However, latest practice promotes specialist, multidisciplinary-led consideration for select patients. This study aimed to evaluate the perioperative and oncological outcomes of synchronous resection in the management of CRLM and CRPM from two tertiary referral centres.MethodThis bi-institutional, retrospective, cohort study included patients undergoing simultaneous liver resection, CRS and HIPEC for metastatic colorectal cancer from 2013 to 2020. Patients treated with ablative liver techniques, staged operative approaches and extra abdominal disease were excluded. Overall survival (OS) and disease-free survival (DFS) rates were assessed. Univariate and multivariate analyses identified variables associated with survival and major morbidity (Clavien-Dindo grade III/IV).ResultsTwenty-three patients were included. The median peritoneal carcinomatosis index (PCI) was 9 (range 0–22). There were two major liver resections and 21 minor resections. CC-0 resections were achieved in all patients. Major morbidity occurred in 7 patients. There were no deaths at 90 days. PCI was independently associated with morbidity (p = 0.04). PCI >10 (p = 0.069), major morbidity (p = 0.083) and presence of KRAS mutation (p = 0.052) approached significance for poor OS. Median follow up was 21 months (4–54 months). Median OS was 37 months, 3-year survival 54%, and median DFS 18 months.ConclusionSynchronous liver resection, cytoreductive surgery and HIPEC is feasible in selected patients with low-volume CRPM and CRLM. Increasing PCI is associated with postoperative major morbidity, and should be considered during operative planning.     

The Impact of Postoperative Conformal Radiotherapy after Radical Surgery on Survival and Recurrence in Pathologic T3N0M0 Esophageal Carcinoma: A Propensity Score-Matched Analysis

IntroductionThe role of conformal radiotherapy (cRT) in thoracic esophageal squamous cell carcinoma (TESCC) has not been addressed in adjuvant settings. The aim of this study was to investigate whether postoperative radiotherapy using cRT after an R0 resection improves outcomes in pT3N0M0 TESCC compared with resection alone.MethodsThis study included 678 patients with pT3N0M0 TESCC who were treated at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2004 to December 2011. The patients were divided into two groups: a surgery plus cRT group (S+cRT group) comprising patients who underwent cRT after an R0 resection and a surgery group (S group), comprising a control group of patients who underwent an R0 resection alone. Propensity score matching was used to create patient groups that were balanced across several covariates (n = 83 in each group). Outcome measures included overall survival (OS), disease-free survival (DFS), and recurrence.ResultsIn the overall study cohort, 5-year OS (75.2% versus 58.5%, p = 0.004) and DFS (71.8% versus 49.2%, p = 0.001) rates were significantly higher in the S+cRT group than in the S group. These data were confirmed in the matched samples (5-year OS, 75.7% versus 58.8% [p = 0.017]; DFS, 71.7% versus 50.3% [p = 0.009]). The overall (p = 0.001) and locoregional (p = 0.004) recurrence rates in the S+cRT group were significantly lower than in the S group. Multivariate Cox analyses in the matched samples revealed that surgery and postoperative cRT were independently associated with longer OS (hazard ratio = 0.505, 95% confidence interval: 0.291–0.876, p = 0.015) and longer DFS (hazard ratio = 0.513, 95% confidence interval: 0.309–0.854, p = 0.010) than resection alone.ConclusionsPostoperative radiotherapy using cRT is strongly associated with improved OS and DFS in patients with pT3N0M0 TESCC. A multicenter, randomized phase III clinical trial is warranted to confirm these findings.     

Intensification of Local Therapy With High Dose Rate,Intraoperative Radiation Therapy (HDR-IORT) and Extended Resection for Locally Advanced and Recurrent Colorectal Cancer

BackgroundWe report our long-term experience with high dose rate intraoperative radiotherapy (HDR-IORT) in a single, quaternary institution.Patients/MethodsFrom 2004 to 2020, 60 HDR-IORT procedures for locally advanced colorectal cancer (LACC) and 81 for locally recurrent colorectal cancer (LRCC) were done in our institution. Preoperative radiotherapy was done prior to majority of the resections (89%, 125/141). Sixty-nine percent (58/84) of the resections involving pelvic exenterations had >3 en bloc organs resected. HDR-IORT was delivered using a Freiburg applicator. A single 10 Gy fraction was delivered. Margin status was R0 and R1 in 54% (76/141) and 46% (65/141) of the resections, respectively.ResultsWith a median follow-up time of 4 years, 3-, 5-, and 7- year, overall survival (OS) rates were 84%, 58%, and 58% for LACC and 68%, 41%, and 37% for LRCC, respectively. Local progression-free survival (LPFS) rates were 97%, 93%, and 93% for LACC and 80%, 80%, 80% for LRCC, respectively. For the LRCC group, an R1 resection was associated with worse OS, LPFS, and progression-free survival (PFS), preoperative EBRT was associated with improved LPFS and PFS, and ≥2 years disease-free interval was associated with improved PFS. The most common severe adverse events were postoperative abscess (n = 25) and bowel obstruction (n = 11). There were 68 grade 3 to 4 and no grade 5 adverse events.ConclusionsFavorable OS and LPFS can be achieved for LACC and LRCC with intensive local therapy. In patients with risk factors for poorer outcomes, optimization of EBRT and IORT, surgical resection, and systemic therapy are required.     

Prognostic factors and outcomes of adult spermatic cord sarcoma. A study from the French Sarcoma Group

PurposeTo evaluate the outcomes of adult patients with spermatic cord sarcoma (SCS).MethodsAll consecutive patients with SCS managed by the French Sarcoma Group from 1980 to 2017 were analysed retrospectively. Multivariate analysis (MVA) was used to identify independent correlates of overall survival (OS), metastasis-free survival (MFS), and local relapse-free survival (LRFS).ResultsA total of 224 patients were recorded. The median age was 65.1 years. Forty-one (20.1%) SCSs were discovered unexpectedly during inguinal hernia surgery. The most common subtypes were liposarcoma (LPS) (73%) and leiomyosarcoma (LMS) (12.5%). The initial treatment was surgery for 218 (97.3%) patients. Forty-two patients (18.8%) received radiotherapy, 17 patients (7.6%) received chemotherapy. The median follow-up was 5.1 years. The median OS was 13.9 years. In MVA, OS decreased significantly with histology (HR, well-differentiated LPS versus others = 0.096; p = 0.0224), high grade (HR, 3 versus 1–2 = 2.7; p = 0.0111), previous cancer and metastasis at diagnosis (HR = 6.8; p = 0.0006). The five-year MFS was 85.9% [95% CI: 79.3–90.6]. In MVA, significant factors associated with MFS were LMS subtype (HR = 4.517; p < 10-4) and grade 3 (HR = 3.664; p < 10-3). The five-year LRFS survival rate was 67.9% [95% CI: 59.6–74.9]. In MVA, significant factors associated with local relapse were margins and wide reresection (WRR) after incomplete resection. OS was not significantly different between patients with initial R0/R1 resection and R2 patients who underwent WRR.ConclusionsUnplanned surgery affected 20.1% of SCSs. A nonreducible painless inguinal lump should suggest a sarcoma. WRR with R0 resection achieved similar OS to patients with correct surgery upfront.     

Treatment and outcome trends and predictors of overall survival of rectal melanoma: Analysis of the National Cancer Database

BackgroundWe aimed to assess characteristics, treatment, and outcomes of rectal melanoma (RM).MethodsThis retrospective cohort study looked at patients with RM from National Cancer Database (2004–2019) analyzed characteristics and outcomes of the entire cohort and across three time periods (2004–2009; 2010–2014; 2015–2019). Main outcome measures were change in treatment and survival trends across time periods and overall survival (OS).Results641 patients (58.5% female; mean age: 68.2 ± 13.6 years) were included. OS rate was 26%; median survival duration was 17.9 (IQR: 15.93–20.67) months. There was a significant decrease in the use of chemotherapy (17.3%–6.6%; p = 0.001) and surgery (62.9%–41.8%; p = 0.00004) but increased use of immunotherapy (11.9%–52%; p < 0.001) across time periods. OS was longer in the last time period than in the first two (21.8 vs 16.8 vs 16.5 months; p = 0.09). Surgical excision was an independent predictor of improved OS (HR = 0.266, 95%CI: 0.089–0.789, p = 0.017) whereas older age (HR = 1.039, 95%CI: 1.007–1.072, p = 0.016), positive resection margins (HR = 5.06, 95%CI: 1.902–13.48, p = 0.001) and metastasis (HR = 34.62, 95%CI: 3.973–301.6, p = 0.001) were predictors of poor survival.ConclusionsOver time, chemotherapy and surgery have been used less often in the treatment of RM while the use of immunotherapy increased by more than four-fold. Older age, surgical treatment, positive resection margins, and metastasis were predictive of survival of RM.     

Relevance of sentinel lymph node biopsy for thick melanoma in the era of immunotherapy

BackgroundSentinel lymph node biopsy provides prognostic information in patients with thick melanoma but is often underutilized. We examine regional lymph node evaluation (RLNE) in patients with thick melanoma and the effect on treatment and overall survival (OS).MethodsPatients with clinical T4N0M0 melanoma were selected from the National Cancer Database (2004–2015). Binary logistic regression analysis was used to identify factors associated with RLNE and treatment. Overall survival analysis was performed.ResultsA total of 14 286 patients with clinical T4N0M0 melanoma were identified; RLNE was performed in 70.2% of patients, and positive LNs were identified in 27.1%. RLNE was more likely in males (OR:1.44, 95%CI: 1.32–1.56, p < .001), and patients treated at academic centers (OR:1.58, 95%CI:1.46–1.71, p < .001). Immunotherapy was more commonly used in patients with RLNE (13.9% vs 3.4%, p < .001) and was associated with positive LNs (OR:2.50, 95%CI:2.19–2.86, p < .001). The 5-year OS for RLNE was 56.9% and for no RLNE was 32.7%. Independent factors associated with better OS were treatment at an academic center (HR:0.88, 95%CI:0.84–0.93, p < .001), and immunotherapy use (HR:0.86, 95%CI:0.76–0.96, p < .001).ConclusionThe use of RLNE in patients with thick melanoma is important for prognosis and to risk stratify patients for selection of adjuvant therapies and clinical trials.     

Perihilar cholangiocarcinoma: A different concept for radical resection

BackgroundLong-term outcomes depend heavily on the possibility of performing radical resection.PurposeTo evaluate long-term results in perihilar cholangiocarcinoma (PHC) patients from the perspective of a new understanding of radical resection.MethodsConsecutive PHC patients who underwent surgical resection at A.V. Vishnevsky Center of Surgery from 2011 to 2018 were retrospectively reviewed. Fifty eight (87.9%) patients underwent hemihepatectomy (14 extended hemihepatectomies), while 2 (3%) underwent extrahepatic bile duct resection only, 6 (9.1%) underwent S4b, and 5 underwent en bloc resection of the extrahepatic bile duct. The influence of the bile duct wedge R status, nodal status, microvascular invasion, microlymphatic invasion, perineural invasion, liver invasion, and surrounding adipose tissue invasion on survival was tested by Cox's models. Survival rates depending on pathological parameter numbers were compared by log-rank tests.ResultsWedge resection, nodal status, microvascular invasion, microlymphatic invasion, perineural invasion, liver invasion, and surrounding adipose tissue invasion served as extended criteria for curability (R+, 1 to 7 parameters). For R0 resection status and R1 resection status (R+1, R+2), 7 and 5 parameters were negative, respectively. For R1+ resection status (R+3, R+4, R+5, R+6, R+7), 3 to 7 parameters were positive. Patients who underwent R0 and R1 resections had 5-year survival rates of 100%; the 1- 2- 3-year survival rates were 63%, 49%, 33% for patients who underwent R1+ resections, respectively. The expanded criteria for determining radical resection levels correlated with long-term outcomes (р = 0.0001).ConclusionThe new concept for radical resection can accurately reflect surgical treatment results and contribute to selecting appropriate adjuvant therapies in PHC patients.Trial registrationThe study was carried out in accordance with the framework of the “Multimodal treatment of primary and secondary malignant tumors of the liver and pancreas” (state registration № 315030310062).     

Implementation of a regional video multidisciplinary team meeting is associated with an improved prognosis for patients with oesophageal cancer A mixed methods approach

BackgroundStudies have shown that multidisciplinary team meetings (MDTM) improve diagnostic work-up and treatment-decisions. This study aims to evaluate the influence of implementing a regional-video-Upper-GI-MDTM (uMDTM) for oesophageal cancer (OC) on the number of patients discussed, treatment-decisions, perspectives of involved clinicians and overall survival (OS) in the Eindhoven Upper-GI Network consisting of 1 resection hospital and 5 referring hospitals.MethodsBetween 2012 and 2018, patients diagnosed with OC within this region, were selected from the Netherlands Cancer Registry(n = 1119). From 2014, an uMDTM was gradually implemented and a mixed-method quantitative and qualitative design was used to analyse changes. Quantitative outcomes were described before and after implementation of the uMDTM. Clinicians were interviewed to assess their perspectives regarding the uMDTM.ResultsAfter participation in the uMDTM more patients were discussed in an MDTM (80%–89%,p < 0.0001) and involvement of a resection centre during the uMDTM increased (43%–82%,p < 0.0001). The proportion of patients diagnosed with potentially curable OC (cT1-4a-x, any cN, cM0) remained stable (59%–61%, p = 0.452). Endoscopic or surgical resections were performed more often (28%–34%,p = 0.034) and the use of best supportive care decreased (21%–15%,p = 0.018). In the qualitative part an improved knowledge, collaboration and discussion was perceived due to implementation of the uMDTM. Three-year OS for all OC patients increased after the implementation of the uMDTM (24%–30%,p = 0.025).ConclusionsImplementation of a regional Upper-GI MDTM was associated with an increase in patients discussed with a resection centre, more curative resections and a better OS. It remains to be elucidated which factors in the clinical pathway explain this observed improved survival.     

Long-Term Outcomes After Sublobar Resection Versus Lobectomy in Patients With Clinical Stage IA Lung Adenocarcinoma Meeting the Node-Negative Criteria Defined by High-Resolution Computed Tomography and [18F]-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography

PurposeTo evaluate long-term outcomes after sublobar resection for patients with clinical stage IA lung adenocarcinoma who met our proposed node-negative (N0) criteria, namely solid component size < 0.8 cm on high-resolution computed tomography (HRCT) or a maximum standardized uptake value (SUV_max) of < 1.5 on [¹⁸F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT).Patients and MethodsBetween April 2006 and December 2010, a total of 347 patients with clinical stage IA lung adenocarcinoma underwent complete resection in two medical centers. Long-term outcomes of patients with disease that met the N0 criteria after sublobar resection were evaluated.ResultsThe disease of 201 patients (57.9%) met the N0 criteria. Meeting N0 criteria was significantly associated with low-grade adenocarcinoma subtype (P < .001) and absence of lymphatic invasion (P < .001), vascular invasion (P < .001), and pleural invasion (P < .001). One patient (0.5%) had lymph node metastasis. The median follow-up period was 86.1 months. There was a significant difference in the overall survival (OS) rates between patients with disease that met the N0 criteria (5-year OS, 93.9%; 10-year OS, 90.3%) and disease that did not (5-year OS, 81.5%; 10-year OS, 64.3%; P < .001). Among patients with disease that met the N0 criteria, there was no significant difference in the OS between those who underwent lobectomy (5-year OS, 94.3%; 10-year OS, 92.6%) and those who underwent sublobar resection (5-year OS, 93.8%; 10-year OS, 89.3%; P = .64).ConclusionsSublobar resection of clinical stage IA lung adenocarcinoma is feasible in selected patients with disease that meets the N0 criteria, with excellent long-term survival.     

Long-term outcomes of resection for locoregional recurrence of colon cancer: A retrospective descriptive cohort study

IntroductionResection for isolated distant recurrence of colon cancer is well accepted. Resection for locoregionally recurrent colon cancer (LRCC) is not well studied. We evaluated the long-term outcomes of curative-intent resection for LRCC.MethodsAll patients undergoing curative-intent resection for LRCC at three specialized cancer centers affiliated with the University of Toronto were identified (1993-2017). Follow-up included serial clinical assessment, colonoscopy, CEA, and cross-sectional imaging. Overall survival (OS), cancer-specific survival (CSS) and time to re-recurrence were estimated using Kaplan-Meier method and cumulative incidence function. The association between resection margins and outcome was assessed with Cox models.Results117 patients were included in the study cohort. Median follow-up was 53 months (IQR: 34-101). OS was 75% (95% CI: 68-84) at 5 years, and 69% (95% CI: 59-79) at 10 years. CSS was 78% (95% CI: 70-86) at 5 years and 72% (95% CI: 63-83) at 10 years. The rate of re-recurrence was 22% (95% CI: 14-31) at 5 years, and 27% (95% CI: 16-39) at 10 years. Negative resection margin (R0) was associated with improved OS (HR 3.33, 95% CI: 1.85–6.00, p < 0.01). There were no postoperative deaths; complications with Clavien-Dindo grade > II occurred in 12% of patients. Perioperative chemotherapy was used in 63% of patients and radiotherapy in 37%.ConclusionIn selected patients with LRCC, excellent OS, CSS and low re-recurrence rates were observed, and R0 resection predicted better outcomes. These findings support consideration of resection for LRCC in fit patients after review at a multidisciplinary cancer conference.     

Surgical treatment of primary locally advanced rectal cancer in Norway

AimsMost reports on locally advanced rectal cancer come from specialized centres, with a selected patient material. The purpose of this study was to examine the results after surgical treatment of patients with locally advanced rectal cancer at a population level.MethodsNational cohort study of 896 patients undergoing surgery for a locally advanced primary adenocarcinoma of the rectum from November 1993 to December 2001.ResultsSurgery with resection was undertaken in 724 patients and 172 patients underwent palliative procedures. Of 557 patients treated for cure, a R0 resection was achieved in 342 (61%). In a multivariate analysis, pre-operative radiotherapy was the only factor with a positive association with R0 status (odds ratio 3.7, 95% confidence interval (CI) 2.1–6.4). Five-year local recurrence rates were 18% (CI 14–23) for R0 resections and 40% (CI 26–52) for R1 resections. Overall 5-year survival rate was 23%; for the group of patients with a R0 resection the survival rate was 49%.ConclusionThe radical resection rate and survival rates in this national study were similar to those reported from specialized centres.     

Association between factor of parotid lymph node and prognosis in parotid cancer

IntroductionSurvival significance of parotid lymph node (LN) factors in parotid cancer remains unclear, our goal was to assess the impact of number, size, and extranodal extension (ENE) of metastatic parotid LNs on prognosis in parotid cancer.Materials and methodsPatients with surgically treated parotid cancer were retrospectively enrolled. Primary outcome variable was recurrence-free survival (RFS) and overall survival (OS). The hazard ratios (HRs) of main predictive variables including the number, size, and ENE of positive parotid LNs on RFS and OS were analyzed using Cox model. The secondary outcome variable was ENE of metastatic parotid LN, its association with clinicopathologic variables were evaluated using Chi-square test.ResultsIn total, 453 patients (186 male and 267 female) were included. The 10-year RFS and OS rates were 73% (95%CI: 69%–77%) and 61% (95%CI: 55%–67%), respectively. In Cox model, compared none parotid LN metastasis, one metastatic parotid LN did not offer additional compromise of RFS (p = 0.224) or OS (p = 0.135), but two or more positive LNs decreased the control of RFS (HR: 2.017; 95%CI: 1.378–4.632) and OS (HR: 2.173; 95%CI: 1.367–4.275). When accounting for the number of metastatic LNs, LN size or ENE was no longer related to RFS or OS. ENE of parotid LN tended to develop if there was presence of T3/4 stage, lymphovascular invasion, high histologic grade, N2/3 stage, and three or more positive parotid LNs.ConclusionQuantitative parotid LN burden but not ENE or LN size is an important determinant of survival in patients with parotid cancer.     

External validation study of the 8th edition of the American Joint Committee on Cancer staging system for perihilar cholangiocarcinoma: a single-center experience in China and proposal for simplification

BackgroundSeveral changes have been made to the primary tumor (T) and lymph node (N) categories in the new 8^th edition of the American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (pCCA). This study was conducted to validate the 8^th edition of the AJCC staging system for pCCA in China.MethodsA total of 335 patients who underwent curative-intent resection for pCCA between January 2010 and December 2018 were retrospectively enrolled. The overall survival (OS) of groups of patients was calculated using the Kaplan-Meier method. The log-rank test was used to compare OS between groups. The concordance index (C-index), Akaike information criteria (AIC), and time-dependent area under receiver operating characteristic (ROC) curve (AUC) were computed to evaluate the discriminatory power of the 8^th and 7^th editions of the AJCC staging system.ResultsThe T category changed in 25 (7.5%) patients, the N category changed in 39 (11.6%) patients, and the tumor-node-metastasis (TNM) stage changed in 157 (46.9%) patients when the 8^th and 7^th editions were compared. No statistically significant difference in survival was observed between T2aN0M0 and T2bN0M0. The C-index of the 8^th edition was 0.609 [95% confidence interval (CI): 0.568–0.650], which was slightly higher than that of the 7^th edition (C-index, 0.599, 95% CI: 0.558–0.640). The time-dependent AUC value also corroborated that the 8^th edition had a better performance than the 7^th edition.ConclusionsThe 8^th edition of the AJCC staging system for pCCA showed a better ability than the 7^th edition to discriminate patient survival. However, further simplification of the 8^th edition is still needed.     

The postoperative part of perioperative chemotherapy fails to provide a survival benefit in completely resected esophagogastric adenocarcinoma

BackgroundBased on two benchmark studies perioperative chemotherapy (CTx) has become standard treatment for locally advanced esophagogastric adenocarcinoma (EGA) in Europe. However, only half of the patients in both studies actually received postoperative CTx (aCTx). Thus, we evaluated the prognostic impact of preoperative CTx (nCTx) and aCTx combined versus nCTx alone. Furthermore, we aimed to identify subgroups potentially beneficial of aCTx and factors associated with its non-administration.MethodsWe retrospectively analyzed 299 consecutive patients with EGA, who underwent complete resection (all M0, R0) after nCTx in our institution and were eligible for aCTx. Patients with and without aCTx were compared regarding clinicopathological data, treatment, morbidity, and long-term prognosis.Results129 patients (43.1%) did not receive aCTx. Administration of aCTx did not significantly improve overall (OS) and recurrence free survival (RFS) (median OS: 78.2 months vs. not reached, p = 0.331; RFS: 43.3 vs. 41.1 months, p = 0.118), but was an independent positive predictor of RFS (HR 1.6 95%CI 1.1–2.5, p = 0.024). aCTx improved RFS in non-intestinal tumors (p = 0.023) and patients receiving FLOT regimen (p = 0.038). By logistic regression analysis factors predictive of non-administration of aCTx were older age (>65 years: OR 3.2, p = 0.028), longer hospital stay (15–28 days: OR 2.6, p = 0.001; >28 days: OR 5.2, p < 0.001), and histopathologic non-response (OR 1.9, p = 0.023).ConclusionAdvanced age, histopathologic non-response, and prolonged convalescence due to postoperative morbidity lead to omission of aCTx. However, this study could not provide evidence to support the beneficial role of aCTx in perioperative chemotherapy regimens for a selected patient collective with EGA and excellent prognosis.