Surgical results of non-small cell lung cancer involving the heart and great vessels

BackgroundThe surgical treatment of advanced non-small-cell-lung-cancer (NSCLC) invading mediastinal organs and great vessels is still controversial. The aim of this multicentre study is to analyse oncological outcomes, surgical outcomes and prognostic factors of patients with NSCLC involving heart and great vessels.Methods362 patients treated surgically for locally advanced T4-NCSLC between 1990 and 2020 were retrospectively reviewed. Patients were divided into five subgroups: pulmonary artery(n = 129), left atrium(n = 82), superior vena cava(n = 80), aorta(n = 43), and multiple vascular structures(n = 28). Resection was complete in 327(90%) patients.ResultsOverall 90-day mortality was 8.8%, influenced by poly-transfusions, pneumonectomy, bronchopleural fistula and previous cardiovascular disease (4.5HR.p = 0.03, 3.7HR p = 0.01, 14.0HR.p < 0.001 and 3.0HR p < 0.01). One-, 3- and 5-year survival rates were 75%, 43%, 33%, respectively and there were significant differences among the five groups(p < 0.001). Survival was significantly affected by induction radiotherapy, nodal status, pTNM-stage and radicality (3.8HR p = 0.03, 2.6HR p = 0.001, 1.6HR p < 0.05 and 1.6HR p < 0.05).ConclusionsSurgery provided acceptable results in selected patients with T4-NSCLC with major vascular infiltration in expert centres. Nodal-status and radicality influenced the overall-survival and disease-free survival. Neoadjuvant chemotherapy appears to have a positive effect on long-term results, particularly in N2-patients.     

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

IntroductionThis 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).MethodsA 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.ResultsPatients 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).ConclusionsThe preoperative CONUT score independently predicts survival outcomes and may serve as a surrogate marker of aggressive systemic disease recurrence in patients with resectable BTC.     

Pelvic Ewing sarcoma: Should all patients receive pre-operative radiotherapy,or should it be delivered selectively?

BackgroundLocally recurrent disease following surgical resection of Ewing sarcoma (ES) confers a poor prognosis. Limited evidence is available evaluating non-selective use of pre-operative radiotherapy (RT) for patients with pelvic ES and its effect on local control and survival.Patients and methods49 consecutive patients with pelvic ES were identified retrospectively from a prospectively collated database. Patients either received non-selective pre-operative RT and surgery (n = 27), or selective post-operative RT (n = 22) (surgery alone (n = 11) or surgery and post-operative RT (n = 11)).ResultsPatients who had non-selective pre-operative radiotherapy appeared to have a higher LRFS, 88.0% compared to 66.5% in the selective RT group (p = 0.096, Kaplan Meier; p = 0.028, Chi-squared). Administration of non-selective, pre-operative RT to all patients with pelvic ES elevates the LFRS to that of the good responder group (≥90% tumour necrosis and margins, p = 0.880). There was no difference in metastasis-free survival, 60.0% and 54.5% (p = 0.728) and overall survival (OS), 57.7% and 63.6% (p = 0.893). The majority of pre-operative RT patients had both good necrosis (≥90%) (p = 0.003) and widely excised tumours, 81.5% vs 59.1% (p = 0.080). Tumour volume ≥250 ml was associated with worse LRFS (p = 0.045) and post-operative complications (p = 0.017). There may be improved LRFS (p = 0.057) with pre-operative proton-beam RT compared to surgery and selective post-operative RT.ConclusionPre-operative photon or proton-beam RT to all pelvic ES may improve LRFS compared to the selective delivery of post-operative RT. Radiotherapy delivered to all patients results in a greater percentage of highly necrotic tumours at surgical excision, enabling a greater proportion of patients with wide resection margins.     

Individualizing surgical treatment based on tumour response following neoadjuvant therapy in T4 primary rectal cancer

BackgroundRectal cancer involving at least one adjacent organ (mrT4b) requires multi-visceral resection to achieve clear resection margin (R0). Performing pelvic compartment preservation according to the tumour response has not been considered. This study assesses the impact of changing the surgical strategy according to tumour response in rectal cancer mrT4b.MethodsPatients with non-metastatic T4b rectal cancer at two tertiary referral centres between 2008 and 2013 were grouped as “Responders” ypT0-3abNx versus “Non-responders” ypT3cd-4Nx and divided into three surgical procedures: total mesorectal excision (TME), extended-TME (eTME) and beyond-TME (b-TME). End-points were circumferential resection margin, postoperative morbidity, definitive stoma formation, 3-years local recurrence (3y-LR) and 3-years disease-free survival (3y-DFS) according to both tumours' response and surgical procedures.ResultsAmong 883 patients with rectal cancer, 101 were included. Responders had a higher rate of induction chemotherapy (59.7% vs. 38.2%; p = 0.04). Morbidity and definitive stoma formation were significantly higher in Non-responders. R0 was not impacted by either the tumour response or the surgical procedures. The 3y-LR was lower in Responders (14%) compared to Non Responders (32%) (HR 1.6; 95% CI: 1.02–2.59; p = 0.041), and was two-fold higher in e-TME compared to b-TME in Non-responders, whereas no difference was found in Responders. The 3y-DFS was higher in Responders irrespective to the surgery (71% vs. 47%; p = 0.07).ConclusionIn Responders, TME or e-TME are technically and oncollogically feasible and should be considered in preferrence to b-TME. In Non-responders, allowing for high rates of morbidity and local recurrence in patients with e-TME, b-TME procedures should be preferred.     

Navigation-assisted pelvic resections and reconstructions for periacetabular chondrosarcomas

ObjectivesSurvival in patients with chondrosarcomas has not improved over 40 years. Although emerging evidence has documented the efficacy of navigation-assisted surgery, the prognostic significance in chondrosarcomas remains unknown. We aimed to assess the clinical benefit of navigation-assisted surgery for pelvic chondrosarcomas involving the peri-acetabulum.MethodsWe studied 50 patients who underwent limb-sparing surgery for periacetabular chondrosarcomas performed with navigation (n = 13) without it (n = 37) at a referral musculoskeletal oncology centre between 2000 and 2015.ResultsThe intralesional resection rates in the navigated and non-navigated groups were 8% (n = 1) and 19% (n = 7), respectively; all bone resection margins were clear in the navigated group. The 5-year cumulative incidence of local recurrence was 23% and 56% in the navigated and non-navigated groups, respectively (p = 0.035). There were no intra-operative complications related to use of navigation. There was a trend toward better functional outcomes in the navigated group (mean MSTS score, 67%) than the non-navigated group (mean MSTS score, 60%; p = 0.412). At a mean follow-up of 63 months, the 5-year disease-specific survival was 76% and 53% in the navigated and non-navigated group, respectively (p = 0.085), whilst the 5-year progression-free survival was 62% and 28% in the navigated and non-navigated group, respectively (p = 0.032).ConclusionThis study confirmed improved local control and progression-free survival with the use of computer navigation in patients with limb-salvage surgery for periacetabular chondrosarcomas, although the advancement in other treatment modalities is required for improvement of disease-specific survival.     

Liver resection in elderly patients with extensive CRLM: Are we offering an adequate treatment? A propensity score matched analysis

BackgroundData on the management of elderly patients with extensive colorectal liver metastases (CRLM) are scarce and conflicting. This study assesses differences in management and long-term oncological outcomes between older and younger patients with CRLM and a high Tumour Burden Score (TBS).MethodsInternational multicentre retrospective study on patients with CRLM and a category 3 TBS, submitted to liver resection. Patients were divided into two groups according to their age (younger and older than 75) and were compared using propensity score matching (PSM) analysis and multivariable regression models. Differences in management and oncological outcomes including recurrence-free survival (RFS) and overall survival (OS) were assessed.ResultsThe study included 386 patients, median follow-up was 48 months. The unmatched comparison revealed a higher ASA score (p = 0.035), less synchronous CRLM (47% vs 68%, p = 0.003), a lower median number of lesions (1 vs 3, p = 0.004) and less perioperative chemotherapy (CTx) (66% vs 88%, p < 0.001) in the elderly group.Despite the absence of CTx being an independent predictor of decreased RFS and OS (HR 0.760, p = 0.044 and HR 0.719, p = 0.049, respectively), the elderly group still received less CTx (OR 0.317, p = 0.001) than the younger group.After PSM (n = 100 patients), the two groups were comparable, however, CTx administration was still significantly lower in the elderly group.ConclusionLiver resection should be considered in patients aged 75 and older, even if they present with extensive liver disease. Despite CTx being associated with improved oncological outcomes, a large percentage of elderly patients with CRLM are undertreated.     

Impact of anatomic resection on long-term survival in patients with hepatocellular carcinoma with T1–T2 disease or microscopic vascular invasion

BackgroundThis study aimed to clarify potential candidates for anatomic resection (AR) among patients with pathological T1–T2 (pT1–T2) hepatocellular carcinoma (HCC) and to determine whether AR is effective for HCC with microscopic vascular invasion (MVI).MethodsWe retrospectively analyzed 288 patients with pT1a (n = 50), pT1b (n = 134) or pT2 (n = 104) HCC who underwent curative-intent resection between 1990 and 2010. Surgical outcomes were compared between patients who underwent AR (n = 189) and those who underwent nonanatomic resection (NAR; n = 99) according to pT category and MVI status.ResultsPatients who underwent AR were more likely to have good hepatic functional reserve and an aggressive primary tumor than those who underwent NAR. When patients were stratified according to pT category, AR had a more favorable impact on survival than NAR only in patients with pT2 HCC in univariate (5-year survival, 51.5% vs. 34.6%; p = 0.010) and multivariate analysis (hazard ratio 0.505; p = 0.014). However, AR had no impact on survival in patients with pT1a or pT1b HCC. In patients with MVI (n = 57), AR achieved better survival than NAR (5-year survival, 52.0% vs. 16.7%; p = 0.019) and was an independent prognostic factor (hazard ratio 0.335; p = 0.020). In patients without MVI (n = 231), there was no significant difference in survival between the two groups (p = 0.221).ConclusionAR was identified as an independent factor in improved survival in patients with pT2 HCC or HCC with MVI.     

Minimum radial margin in pelvic exenteration for locally advanced or recurrent rectal cancer

PurposeThe aim of this study was to clarify the suitable radial margin (RM) for favourable outcomes after pelvic exenteration (PE), focusing on the discrepancy between the concepts of circumferential resection margin (CRM) and traditional R status.MethodsSeventy-three patients with locally advanced (LARC, n = 24) or locally recurrent rectal cancer (LRRC, n = 49) who underwent PE between 2006 and 2018 were retrospectively analysed. Patients were histologically classified into the following 3 groups; wide RM (≥1 mm, n = 45), narrow RM (0–1 mm, n = 10), and exposed RM (n = 18). The analysis was performed not only in the entire cohort but also in each disease group separately.ResultsThe rates of traditional R0 (RM > 0 mm) and wide RM were 75.3% and 61.6%, respectively, resulting in the discrepancy rate of 13.7% between the two concepts. Preoperative radiotherapy was given in 12.3%. In the entire cohort, the local recurrence and overall survival (OS) rates for narrow RMs were significantly worse than those for wide RMs (p < 0.001 and p = 0.002), but were similar to those for exposed RMs. In both LARC and LRRC, RM < 1 mm resulted in significantly worse local recurrence and OS rates compared to the wide RMs. Multivariate analysis showed that RM < 1 mm was an independent risk factor for local recurrence in both LARC (HR 15.850, p = 0.015) and LRRC (HR 4.874, p = 0.005).ConclusionsNarrow and exposed RMs had an almost equal impact on local recurrence and poor OS after PE. Preoperative radiotherapy might have a key role to ensure a wide RM.     

Sarcopenia and primary tumor location influence patients outcome after liver resection for colorectal liver metastases

IntroductionRight-sided and left-sided colorectal cancer (CRC) is known to differ in their molecular carcinogenic pathways. The prevalence of sarcopenia is known to worsen the outcome after hepatic resection. We sought to investigate the prevalence of sarcopenia and its prognostic application according to the primary CRC tumor site.Methods355 patients (62% male) who underwent liver resection in our center were identified. Clinicopathologic characteristics and long-term outcomes were stratified by sarcopenia and primary tumor location (right-sided vs. left-sided). Tumors in the coecum, right sided and transverse colon were defined as right-sided, tumors in the left colon and rectum were defined as left-sided. Sarcopenia was assessed using the skeletal muscle index (SMI) with a measurement of the skeletal muscle area at the level L3.ResultsPatients who underwent right sided colectomy (n = 233, 65%) showed a higher prevalence of sarcopenia (35.2% vs. 23.9%, p = 0.03). These patients also had higher chances for postoperative complications with Clavien Dindo >3 (OR 1.21 CI95% 0.9–1.81, p = 0.05) and higher odds for mortality related to CRC (HR 1.2 CI95% 0.8–1.8, p = 0.03).On multivariable analysis prevalence of sarcopenia remained independently associated with worse overall survival and disease free survival (overall survival: HR 1.47 CI 95% 1.03–2.46, p = 0.03; HR 1.74 CI95% 1.09–3.4, p = 0.05 respectively).ConclusionSarcopenia is known to have a worse prognosis in patients with CRLM and CRC. Depending on the primary location sarcopenia has a variable effect on the outcome after liver resection.     

The role of surgery for locally recurrent and second recurrent rectal cancer with metastatic disease

BackgroundThe role of surgery for locally recurrent rectal cancer (LRRC) with resectable distant metastases or second LRRC remains unclear. This study aimed to clarify the influence of synchronous distant metastases (SDMs), a history of distant metastasis resection (HDMR), and a second LRRC on the outcome.MethodsThe long-term outcomes of 70 surgically treated patients with LRRC between 2006 and 2018 were compared by SDM (n = 10), HDMR (n = 17), and second LRRC (n = 7).ResultsAmong the 10 patients with SDM, 4 patients underwent simultaneous resection, whereas the other 6 underwent staged resection with distant first approach. Recurrence developed in 9 patients, of which 2 patients with liver re-resection achieved long-term survival without cancer. The patients with and without SDM had equivalent 5-year overall survival rate (40.5% vs. 53.3%, p = 0.519); however, patients with SDM had a worse 3-year recurrence-free survival rate than those without SDM (10.0% vs. 37.5%, p = 0.031). Multivariate analysis showed that primary non-sphincter-preserving surgery, second LRRC, and R1 resection were independent risk factors for overall survival. Similarly, primary non-sphincter-preserving surgery, second LRRC, SDM, and R1 resection were risk factors for recurrence-free survival.ConclusionsPatients with SDM might still be suitable to undergo salvage surgery and achieve favourable overall survival. Distant metastasectomy should be performed first, followed by a sufficient interval to avoid unnecessary LRRC resection in uncurable patients. An HDMR should not be taken into consideration when making surgical plans. Surgical indication of second LRRC should be strict, especially in referred patients.     

IOeRT in retroperitoneal sarcoma: Towards more organ preservation with comparable oncological outcomes

BackgroundRetroperitoneal sarcomas (RPS) present a surgical challenge with high rates of local recurrence (LR). We investigated the role of intraoperative electron radiotherapy (IOeRT) in reducing LR after surgical resection of RPS.MethodsA retrospective analysis of all patients who underwent surgical resection for RPS between 2014 and 2021 at a tertiary academic referral center (n = 172). Patients included underwent surgical resection of their RPS and received IOeRT (n = 36) and were compared by case control matching to patients with similar tumor characteristics (recurrence status and tumor grade) that did not receive IOeRT (n = 36).ResultsThe median length of hospitalization was 8 days (range, 4–34) in the IOeRT group and 10 days (range, 2–42) in the non-IOeRT group (p = 0.25). The mean operating room (OR) time was 4h (±1.3) and 4h (±1.9) in the IOeRT and non-IOeRT groups respectively, (p = 0.37). Complete resection with R0 margins was achieved in 30 patients (83.3%) and 24 patients (66.6%) in the IOeRT and non-IOeRT groups, respectively (p = 0.1). R1 resection was achieved in 6 patients (16.6%) and 12 patients (33.3%) respectively, (p = 0.1). The resected organ weighted score was significantly different between the groups; score 0 observed in 19 (52.7%) patients in the IOeRT group and 3 (8.3%) in the non-IOeRT group (p < 0.001), score 1 observed in 7 (19.4%) in the IOeRT group and 17 (47.2%) in the non-IOeRT group (p = 0.012). The rate of severe complications (CD score>3) did not differ between the groups, 5 (13.8%) patients in the IOeRT group and 9 (25%) patients in the non-IOeRT group (p = 0.23). No radiation associated complications were noted. The 2-year local recurrence free survival (LRFS) was 75.9% in the IOeRT group and 60.3% in the non-IOeRT group (p = 0.4). The 2-year IOeRT field recurrent free survival (IRFS) was 88.4% in the IOeRT group and 60.3% in the non-IOeRT group (p = 0.04).ConclusionsThe use of IOeRT did not increase the rate of surgical complications and was associated with superior local control in the radiation field, improved organ preservation without an impact on overall survival.     

Surgical treatment of breast cancer liver metastases - A nationwide registry-based case control study

IntroductionThe benefit of liver resection or ablation for breast cancer liver metastases (BCLM) remains unclear. The aim of the study was to determine survival after isolated BCLM in nationwide cohorts and compare surgical versus systemic treatment regimens.Materials and methodsThe Swedish register for cancer in the liver and the bile ducts (SweLiv) and the National register for breast cancer (NBCR) was studied to identify patients with 1–5 BCLM without extrahepatic spread diagnosed 2009–2016. Data from the registers were validated and completed by review of medical records. A Kaplan-Meier plot and log rank test were used to analyse survival. Prognostic and predictive factors were evaluated by Cox regression analysis.ResultsA surgical cohort (n = 29) was identified and compared to a control cohort (n = 33) receiving systemic treatment only. There was no 90-day mortality after surgery. Median survival from BCLM diagnosis was 77 months (95% CI 41–113) in the surgical cohort and 28 months (95% CI 13–43) in the control cohort, (p = 0.004). There was a longer disease-free interval and more oestrogen receptor positive tumours in the surgical cohort. Surgery was a significant positive predictive factor in univariate analysis while a multivariable analysis resulted in HR 0.478 (CI 0.193–1.181, p = 0.110) for surgical treatment.ConclusionSurgery for BCLM is safe and might provide a survival benefit in selected patients but prospective trials are warranted to avoid selection bias.     

Therapeutic neck dissection in head and neck melanoma patients: Comparing extent of surgery and clinical outcome in two cohorts

BackgroundThe extent of surgical management of regional lymph nodes in the treatment of cutaneous head and neck melanoma on and anterior to O'Brien's watershed line is controversial. By comparing patients' cohorts of two separate melanoma expert centers we investigate the effectiveness of comprehensive versus (super-) selective neck dissection approach.MethodsSixty patients with macroscopic (palpable) neck node metastases (N2b) from anterior scalp and face melanoma were retrospectively studied. Forty therapeutic modified radical neck dissections (MRND; levels I–V) combined with elective parotidectomy from The Netherlands Cancer Institute (NCI) were compared with 16 (super-) selective neck dissections [(S)SND; 3–4 levels] and 4 solely MRNDs from Erasmus Medical Center (EMC). Cohorts were analyzed for site of recurrence, overall survival (OS), melanoma-specific survival (MSS), and disease-free survival (DFS).ResultsClinical characteristics of patients were equal in both groups. In the NCI cohort 62.5% (n = 25) of patients recurred versus 65% (n = 13) in the EMC cohort. None of the NCI recurrences affected the parotid gland in contrast to 3 patients in the EMC group. Survival characteristics were not different between the two groups: OS (p = 0.56), MSS (p = 0.98), DFS (p = 0.92).ConclusionThis study does not support to continue the practice of routine elective parotidectomy and MRND in melanoma patients undergoing a lymph node dissection for macroscopic (palpable) nodal disease and justifies (S)SND.     

Pancreatectomy with venous vascular resection for pancreatic cancer: Impact of types of vein resection on timing and pattern of recurrence

IntroductionFew studies analysed the impact of different venous resection techniques on recurrence in patients with pancreatic ductal adenocarcinoma (PDAC). Primary aim was to compare local recurrence rate and disease-free survival (DFS) between patients who underwent pancreatectomy with tangential versus segmental resection of portal vein/superior mesenteric vein.Materials and methodsAll consecutive patients who underwent pancreatectomy with venous resection for PDAC between 2009 and 2019 were included. A propensity score matching (PSM) was used to reduce the effect of treatment selection bias.ResultsOverall, 120 patients (68%) underwent pancreatectomy with tangential venous resection and 57 patients (32%) were submitted to pancreatectomy with segmental venous resection. After a median follow-up of 24 months, local recurrence was comparable between the two groups (tangential: n = 32/120, 26.7% versus segmental: n = 10/57, 17.5%; p = 0.58). The median DFS was 17 months (IQR 9–31) in patients who underwent tangential resection, as compared to 12 months (IQR 5–21) in those who underwent segmental resection (p = 0.049). After PSM (n = 106), the median DFS was 18 months (IQR 9–26) in the tangential resection group, and 12 months (IQR 5–21) in the segmental resection group (p = 0.17). In the PSM population, lymph node ratio (HR 4.83; p = 0.028) and tumor size >25 mm (HR 3.26; p = 0.007) were identified as determinants of local recurrence.ConclusionTangential venous resections are not associated with a higher rate of local recurrence. Long-term outcomes are more related to tumors characteristics than to venous resection techniques. A step-up approach to vein resection, with tangential resection being performed whenever technically feasible, should be strongly encouraged.     

Survival following surgical treatment for anorectal melanoma seems similar for local excision and extensive resection regardless of nodal involvement

BackgroundAnorectal melanoma is a rare malignancy with a dismal prognosis. The purpose of this study was to investigate whether the survival per stage is influenced by the surgical approaches (local excision or extensive resection), to assess prognostic factors of survival, and to answer the question whether the practiced surgical approaches changed over time.MethodsDutch cancer registry organizations (IKNL and PALGA) were queried for all patients with a diagnosis of anorectal melanoma (1989–2019). Patients with disseminated disease at diagnosis were excluded. Survival outcomes were compared for the two surgical approaches stratified by stage (clinical node negative (cN0) and clinical node positive (cN+)) and date of diagnosis.ResultsA total of 103 patients were included in this study. In both cN0 and cN+ patients the surgical strategy did not significantly influence survival (cN0: 21.7% 5-year survival, median 25 months for local excision versus 13.7% 5-year survival, median 17 months for extensive resection (p = 0.228), cN+: 11.1% 5-year survival for local excision, median 17 months versus 8.7% 5-year survival, median 14 months for extensive resection (p = 0.741)). Stage and date of diagnosis showed to be prognostic factors of survival. The ratio between the two surgical approaches was unchanged over three decades.ConclusionsExtensive resection does not seem to improve survival in both cN0 and cN+ anorectal melanoma patients compared to local excision. However in the past three decades no shift towards local excision has been found. cN+ stage and an older date of diagnosis are predictors for worse survival.     

Upfront primary tumour resection and survival in synchronous metastatic colorectal cancer according to primary tumour location and RAS status: Pooled analysis of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

IntroductionRetrospective studies and meta-analyses suggest that upfront primary tumour resection (UPTR) confers a survival benefit in patients with asymptomatic unresectable metastatic colorectal cancer (mCRC) undergoing chemotherapy, however a consensus of its role in routine clinical practice in the current era of targeted therapies is lacking. This retrospective study aimed to analyse the survival benefit of UPTR in terms of tumour location and mutational status, in patients with synchronous mCRC receiving chemotherapy and targeted therapy.Patients and methodsSurvival was analysed in a pooled cohort of synchronous mCRC patients treated with a first-line anti-VEGF or anti-EGFR inhibitor in seven trials of the Spanish TTD group, according to UPTR, tumour-sidedness and mutational profiling.ResultsOf 1334 eligible patients, 642 (48%) had undergone UPTR. UPTR was associated with significantly longer overall survival (OS; 25.0 vs 20.3 months; HR 1.30, 95%CI 1.15–1.48; p < 0.0001). UPTR was associated with significant OS benefit in both left-sided (HR 1.38, 95%CI 1.13–1.69; p = 0.002) and right-sided (HR 1.39, 95%CI 1.00–1.94; p = 0.049) tumours, RASwt (HR 1.29, 95%CI 1.05–1.60; p = 0.016) and BRAFwt (HR 1.49, 95%CI 1.21–1.84; p = 0.0002) tumours, and treatment with anti-EGFRs (HR 1.47, 95%CI 1.13–1.92; p = 0.004) and anti-VEGFs (HR 1.25, 95%CI 1.08–1.44; p = 0.003). Multivariate analysis identified number of metastatic sites, RAS status, primary tumour location and UPTR as independent prognostic factors for OS.ConclusionConsidering the selection bias inherent to this study, our results support UPTR before first-line anti-EGFR or anti-VEGF targeted therapy in right and left-sided asymptomatic unresectable synchronous mCRC patients. RAS/BRAF mutational status may also influence UPTR function.     

Laparoscopic versus open resection for rectal cancer: An individual patient data meta analysis of randomized controlled trials

Background and aimsThe role of laparoscopic rectal cancer resection remains controversial. Thus, we aimed to conduct a one-stage meta-analysis with reconstructed patient-level data using randomized trial data to compare long-term oncologic efficacy of laparoscopic and open surgical resection for rectal cancer.MethodsMedline, EMBASE and Scopus were searched for articles comparing laparoscopic with open surgery for rectal cancer. Primary outcome was disease free survival (DFS) while secondary outcome was overall survival (OS). One-stage meta-analysis was conducted using patient-level survival data reconstructed from Kaplan-Meier curves with Web Plot Digitizer. Shared-frailty and stratified Cox models were fitted to compare survival endpoints.ResultsSeven randomized trials involving 1767 laparoscopic and 1293 open resections for rectal cancer were included. There were no significant differences between both groups for DFS and OS with respective hazard ratio estimates of 0.91 (95% CI: 0.78–1.06, p = 0.241) and 0.86 (95% CI:0.73–1.02, p = 0.090). Sensitivity analysis for non-metastatic patients and patients with mid and lower rectal cancer showed no significant differences in OS and DFS between both surgical approaches. In the laparoscopic arm, improved DFS was noted for stage II (HR: 0.73, 95% CI:0.54–0.98, p = 0.036) and stage III rectal cancers (HR: 0.74, 95% CI:0.55–0.99, p = 0.041).ConclusionsThis meta-analysis concludes that laparoscopic rectal cancer resection does not compromise long-term oncologic outcomes compared with open surgery with potential survival benefits for a minimal access approach in patients with stage II and III rectal cancer.     

Outcome of Patients With Resected Early-Stage Non-small Cell Lung Cancer and EGFR Mutations: Results From the IFCT Biomarkers France Study

IntroductionMolecular profile of resected stage I–II non-small cell lung cancer (NSCLC) would help refine prognosis and personalize induction or adjuvant strategies. We sought to report the molecular profile of resected stage I–II NSCLC and analyzed the impact of epidermal growth factor receptor (EGFR) mutations on outcomes in a Western population.Patients and MethodsSurgical cases were identified from Biomarkers France study, a nationwide prospective study including NSCLC patients screened for EGFR, HER2, KRAS, BRAF, PIK3CA, ALK alterations from 2012 to 2013. Among surgical patients, clinical charts of the largest centers were reviewed in order to analyze the prognostic impact of EGFR mutations.ResultsIn the BMF database (n = 17.636), surgical patients (n = 854) were characterized by a higher proportion of EGFR mutations than nonsurgical patients (12.9% vs. 10.2%, P = .025), while the other molecular alterations did not differ. The proportion of EGFR mutations was 27% in women undergoing surgery. In the study group (n = 293; EGFR wild type, n = 235; usual mutation, n = 50; rare mutation, n = 8), after a median follow-up of 67 months, 215 patients (74.4%) had not relapsed. No difference was found between EGFR-mutant and EGFR-wt tumors regarding recurrence site, disease-free survival, and overall survival. The 5-year disease-free survival and overall survival after surgical resection of stage I-II EGFR-mutated tumors were 65% and 75%, respectively.ConclusionIn resected stage I to II NSCLC, EGFR mutations were found in 12.9% of cases, associated with a 5-year overall survival of 75%, with no impact on recurrence site, disease-free survival, and overall survival.     

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.     

Quality of treatment and surgical approach for rectal gastrointestinal stromal tumour (GIST) in a large European cohort

BackgroundRectal gastrointestinal stromal tumours (GISTs) are rare tumours. Variability in the management may influence outcome, but there is a lack of understanding regarding contemporary variance in care. A multicenter, international, retrospective cohort study was performed to elucidate characteristics and outcomes of rectal GIST in European practice, with particular reference to surgical approach.MethodsAll rectal GIST patients diagnosed between 2009 and 2018 were identified from five European databases. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. Possible confounders were identified using Cox regression analyses.ResultsFrom 210 patients, 155 patients had surgery. The three main types of surgery were local tumour resection (LTR, n = 46), low anterior resection (LAR, n = 31) and abdomino-perineal resection (APR, n = 32). Most patients received neoadjuvant (65%) and/or adjuvant imatinib therapy (66%). Local recurrence rate after surgery was 15% and overall recurrence rate 28%. No significant differences were found in terms of RFS nor OS between LTR, LAR and APR. However, locally resected tumours were smaller, while LAR and APR patients more often received perioperative imatinib. General hospitals treated smaller GISTs, offered imatinib less frequently, and had a higher tumour rupture rate. In the multivariate analysis in the group having LTR, APR or LAR, the only significant prognostic factor for local recurrence was higher age (HR 1.06, CI 1.00–1.12, p = 0.048).ConclusionsIn European clinical practice for rectal GIST, LTR, LAR and APR have comparable local control. Multimodal approach is higher and tumour rupture less frequent in specialist centres compared to general hospitals.