Validation of a supplementary condition of eighth AJCC staging system for stage II hepatocellular carcinoma

IntroductionThe eighth American Joint Committee on Cancer (AJCC) staging system was flawed regarding the prognosis of stage II hepatocellular carcinoma (HCC). The aims of this study were to reveal the defect and make updates.MethodsClinical and survival data of HCC patients from the Surveillance, Epidemiology, and End Results database were used. We re-classified stage II into T2aN0M0 (tumors >2 cm with vascular invasion) and T2bN0M0 (multiple tumors ≤5 cm). The Kaplan–Meier method and log-rank test were used to estimate differences in overall survival (OS). Three propensity score matching analyses without (PSM1) or with (PSM2 and PSM3) consideration of surgical treatment were performed. Cox regression was used to reveal risk factors.ResultsHCC patients identified as T1bN0M0, T2aN0M0, T2bN0M0, and T3N0M0 were recruited. OS in T2N0M0 was consistent with the eighth AJCC staging system after PSM1. T2bN0M0 had increased OS compared with T2aN0M0 after PSM2 (hazard ratio [HR] = 1.36; 95% confidence interval [CI] = 1.06–1.73; P = 0.0141) or PSM3 (HR = 1.18; 95%CI = 1.01–1.37; P = 0.0283). No survival benefit existed between T1bN0M0 and T2bN0M0 after PSM2 (HR = 0.92; 95%CI = 0.80–1.05; P = 0.2171) or PSM3 (HR = 0.92; 95%CI = 0.84–1.01; P = 0.0888). Compared with T2aN0M0, T3N0M0 had shorter OS after PSM2 (HR = 0.64; 95%CI = 0.50–0.82; P = 0.0003) or PSM3 (HR = 0.63; 95%CI = 0.54–0.73; P < 0.0001). Cox regression analysis revealed that surgical treatment was associated with better prognosis (HR = 0.3; 95%CI = 0.3–0.4; P < 0.001).ConclusionsThe current staging for T2N0M0 is imprecise because surgical treatment is not adequately evaluated and would be ineffective if the proportion of T2bN0M0 patients with surgical treatment was increased.     

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.     

Synergistic effect of clinicopathological factors on mortality risk in patients with differentiated thyroid cancer: An analysis using the SEER database

ObjectivesIn this study, we analyzed the effects of histology subtypes, lymph node N-stages, and the presence of extrathyroidal extensions on cancer-specific survival (CSS) and overall survival (OS) in patients with differentiated thyroid cancer.Materials and methodsCox proportional hazards regression analyses were carried out to evaluate the correlations between clinicopathological factors and CSS/OS. The combined effects of these factors on CSS and OS were then analyzed to determine the relative excess risk, attributable proportion, and synergy index. Kaplan-Meier curves were used to evaluate the mortality rate.ResultsA total of 86033 cases were included in the analysis. Histology subtype, N-stage, and extrathyroidal extension were all found to be risk factors for CSS (hazard ratio [HR] = 1.8, 95% confidence intervals [CI]: 1.4–2.3, p < 0.001; HR = 1.9, 95% CI: 1.6–2.3, p < 0.001; HR = 1.4, 95% CI: 1.0–1.9, p = 0.035, respectively). The risk factors for OS were histology subtype and N-stage (HR = 1.3, 95% CI; 1.2–1.5, p < 0.001; HR = 1. 4, 95% CI: 1.3–1.5, p < 0.001, respectively) but not extrathyroidal extension (HR = 1.1, 95% CI: 0.9–1.3, p = 0.228). Furthermore, histology subtype and N-stage, histology subtype and extrathyroidal extension, and N stage and extrathyroidal extension (relative excess risk, attributable proportion, and synergy index: 48.8, 0.9, 7.6; 50.2, 0.7, 3.9; 7.0, 0.3, 1.6; respectively) were found to have significant synergistic effects.ConclusionPatients with follicular thyroid carcinoma (FTC) and extrathyroidal extension or lymph node metastasis are at a higher risk of mortality. Histology subtype, N-stage, and extrathyroidal extension appear to have synergistic effects on the increased risk of poor CSS in patients. This result can in the further development of treatment guidelines to improve the outcome of FTC patients.     

Prognostic and predictive effects of diabetes,hypertension, and coronary artery disease among women on extended adjuvant letrozole: NCIC CTG MA.17

BackgroundWomen with breast cancer and diabetes mellitus (DM) have poorer survival. Mechanisms include insulin dysregulation and/or DM related co-morbidities (CM). In MA.17 adjuvant letrozole (LET) after 5 years of tamoxifen (TAM) reduced the risk of recurrence and improved survival. We evaluated DM, hypertension (HTN), and coronary artery disease (CAD) as prognostic and predictive factors in MA.17.Patients and methodsDisease free survival, distant disease free survival (DDFS) and overall survival (OS) were compared using Cox regression model adjusting for other prognostic factors: in women treated by placebo (PLAC) based on the presence or absence of baseline DM (n = 462), HTN (n = 1627), CAD (n = 604) or any one of these CM (n = 2049), and between LET and PLAC groups in each CM. Analyses based on nodal status were performed.ResultsDM was neither prognostic nor predictive for women on extended LET. Women with one CM had similar outcomes on LET compared to women free of CM. For node positive women, the difference between LET and PLAC in DDFS was greater among women with one CM (hazard ratio [HR] = 0.30 [0.15–0.60], p = 0.001) compared to those without CM (HR = 0.72 [0.45–1.16], p = 0.17, p interaction = 0.04). Women on PLAC with HTN trended towards lower DDFS (HR = 1.50 [0.98–2.3], p = 0.06) and OS (HR = 1.61 [0.95–2.72], p = 0.08) than non-HTN women. HTN women had better DDFS on LET than non-HTN women. Women with one CM on PLAC had lower OS (HR = 2.10 [1.26–3.51], p = 0.004) than those free of CM.ConclusionsDM was not prognostic or predictive of outcomes. Women with CM who remain disease free after 5 years of TAM should be offered LET. HTN trended towards a negative prognosticator and outcomes among this group were improved on LET. More studies are needed to assess impact of adrenergic stimulation as a possible link to poorer breast cancer outcomes.     

Determining the role of adjuvant therapy in Invasive Intraductal Papillary Mucinous Neoplasms; a systematic review and meta-analysis

BackgroundConflicting evidence exists regarding the role of adjuvant therapy for Invasive Intraductal Papillary Mucinous Neoplasms (i-IPMN). This meta-analysis assessed whether adjuvant therapy improves Overall Survival (OS) in patients with resected i-IPMN.MethodsA systematic review and meta-analysis was performed. The primary endpoint was the effect of adjuvant therapy on OS. Secondary endpoint evaluated adjuvant therapy with regard to nodal disease, positive resection margins, tumour grade and differentiation. A meta-analysis of pooled hazard ratios (HRs) with an inverse variance and a random-effects model was performed. Risk of bias was determined with the GRADE approach and MINORS criteria.ResultsTen articles with a total of 3252 patients were included. No statistically significant difference in the OS was noted with adjuvant therapy for i-IPMN in the entire cohort (HR = 1; 95% CI = 0.75–1.35; P = 0.98). However, a survival benefit was noted in a subgroup of patients with an aggressive disease phenotype; nodal involvement (HR = 0.56; 95% CI = 0.39–0.79; P = 0.001) and advanced staged tumours (≥stage 2, HR = 1.42; 95% CI = 1.11–1.82; P = 0.005)ConclusionsThe concurrent evidence base for adjuvant therapy for i-IPMN is limited. After acknowledging the limitations of the data, the current literature suggests that adjuvant therapy should be reserved for patients with resected i-IPMN that have adverse tumour biology.     

Long-term oncological safety of minimally invasive surgery in high-risk endometrial cancer

BackgroundSeveral studies showed that women with low-risk endometrial cancers staged by minimally invasive surgery (MIS) experience fewer postoperative complications compared to those staged by laparotomy with similar disease-free survival (DFS) and overall survival (OS). However, high-risk patients were poorly represented. In this study, we compared DFS and OS in high-risk endometrial cancer patients who underwent surgical staging via MIS versus laparotomy.MethodsUsing a multicentric database, we compared DFS and OS between 114 patients with high-risk histology who underwent surgical staging via MIS and 114 patients who underwent laparotomy. Patients were matched for age, tumour type, FIGO stage and management criteria.ResultsAmong the 114 patients who underwent MIS, 93 underwent laparoscopy and 21 robotic surgery. Groups were comparable for stage, body mass index, histology and adjuvant therapies. However, patients in the MIS group underwent paraaortic lymphadenectomy less frequently (13% versus 29%; p = 0.01), had less lymph nodes removed (19.0 versus 28.6; p < 0.01) and had lower mean tumour size (30 versus 40 mm; p < 0.01). With a median follow-up time of 49 months, DFS and OS were not significantly different between the surgical cohorts. In multivariable analysis, both higher stage (hazard ratio [HR] = 2.2) and histology (HR = 4.9) were associated with DFS in contrast to surgical procedure (HR = 0.9).ConclusionsBeyond the benefit of MIS on immediate surgical outcome, our results show that fear for a poor long-term outcome should not be the reason to refrain from MIS in patients with high-risk endometrial cancer.     

Multimodality treatment of undifferentiated pleomorphic soft tissue sarcoma of the extremity (eUPS) in the elderly

IntroductionThis subgroup analysis of undifferentiated pleomorphic soft tissue sarcoma of the extremity (eUPS) from the PERSARC collaborative group aimed to achieve a more personalized multimodality treatment approach for primary eUPS in elderly patients.Material and methodsA multicenter retrospective study including primary high-grade eUPS surgically treated with curative intent between 2000 and 2016. Overall survival (OS), local recurrence (LR) and distant metastasis (DM) curves were calculated by Kaplan Meier analysis. Cox proportional hazard models were used to determine the effect of radiotherapy.ResultsFrom a total of 2511 patients with extremity soft tissue sarcoma (eSTS) of the PERSARC study collaborative; 703 patients with eUPS were included in this study. In elderly patients with eUPS 5-year OS, LR and DM were 35.4 (95%CI 29.3–42.8), 17.7 (95%CI 12.7–22.6) and 24.6 (95%CI 19.1–30.1). eUPS was significantly less treated with radiotherapy compared with other eSTS, especially in elderly patients. Patients with R1-R2 margins treated with radiotherapy had about half the risk of developing LR compared with patients treated without radiotherapy (HR = 0.454, p = 0.033).ConclusionElderly patients with eUPS were less often treated with radiotherapy and showed higher LR. Nowadays, given an increasing life expectancy in elderly patients, multimodality treatment should be considered.     

The importance of surgical resection in the management of rectal sarcoma: A national cancer database analysis of 133 cases

Background and purposeRectal sarcomas (RS) are rare malignant tumors with a very poor prognosis. This study aimed to assess the characteristics, treatment, and outcomes of RS in the United States.MethodsThis study was a retrospective analysis of the National Cancer Database (NCDB) from 2004 to 2019 of patients with a diagnosis of RS. The main outcome measures were overall survival (OS) and its predictors.Results133 RS patients (39.1% female) with a mean age of 65.7 ± 15.6 years were included in the study. Mean tumor size was 6.1 ± 3 cm. The crude OS rate was 22.5% and median survival duration was 10.1 (IQR: 3.2–21) months. Factors associated with an improved OS on were private insurance (HR = 0.23, p = 0.001) and undergoing surgery (HR 0.23, p < 0.001), Factors associated with poor survival were age (HR 1.02, p = 0.005), male sex (HR 2.27, p = 0.001), Charlson score of 3 (HR 5.17, p = 0.003), and positive resection margins (HR: 2.64, p = 0.01). Multivariate Cox regression analysis revealed that male sex (HR 2.16, p = 0.04) and positive resection margins (HR 2.31, p = 0.03) were predictors of poor survival whereas surgery was an independent predictor of improved OS (HR 0.321, p < 0.001)ConclusionsRS is a very rare rectal malignancy with an even poorer prognosis than previously reported. However, undergoing surgery with curative intent while obtaining negative margins may confer better OS.     

Risk factors for local recurrence and long term survival after minimally invasive intersphincteric resection for very low rectal cancer: Multivariate analysis in 161 patients

IntroductionIntersphincteric resection (ISR) is the ultimate anal-sparing technique as an alternative to abdominoperineal resection in selected patients. Oncological safety is still debated. This study analyses long-term oncological results and evaluates risk factors for local recurrence (LR) and overall survival (OS) after minimally-invasive ISR.Materials and methodsRetrospective single-center data were collected from a prospectively maintained colorectal database. A total of 161 patients underwent ISR between 2008 and 2018. OS and local recurrence-free survival (LRFS) were assessed using Kaplan-Meier analysis (log-rank test). Risk factors for OS and LRFS were assessed with Cox-regression analysis.ResultsMedian follow-up was 55 months. LR occurred in 18 patients. OS and LRFS rates at 1, 3, and 5 years were 96%, 91%, and 80% and 96%, 89%, and 87%, respectively. Tumor size (p = 0.035) and clinical T-stage (p = 0.029) were risk factors for LRFS on univariate analysis. On multivariate analysis, tumor size (HR 2.546 (95% CI: 0.976–6.637); p = 0.056) and clinical T-stage (HR 3.296 (95% CI: 0.941–11.549); p = 0.062) were not significant. Preoperative CEA (p < 0.001), pathological T-stage (p = 0.033), pathological N-stage (p = 0.016) and adjuvant treatment (p = 0.008) were prognostic factors for OS on univariate analysis. Preoperative CEA (HR 4.453 (95% CI: 2.015–9.838); p < 0.001) was a prognostic factor on multivariate analysis.ConclusionsThis study confirms the oncological safety of minimally-invasive ISR for locally advanced low-lying rectal tumors when performed in experienced centers. Despite not a risk factor for LR, tumor size and, locally advanced T-stage with anterior involvement should be carefully evaluated for optimal surgical strategy. Preoperative CEA is a prognostic factor for OS.     

Gemcitabine–erlotinib versus gemcitabine–erlotinib–capecitabine in the first-line treatment of patients with metastatic pancreatic cancer: Efficacy and safety results of a phase IIb randomised study from the Spanish TTD Collaborative Group

BackgroundGemcitabine and erlotinib have shown a survival benefit in the first-line setting in metastatic pancreatic cancer (mPC). The aim of this study was to assess whether combining capecitabine (C) with gemcitabine + erlotinib (GE) was safe and effective versus GE in patients with mPC.Patients and methodsPreviously untreated mPC patients were randomised to receive G (1000 mg/m², days 1, 8, 15) + E (100 mg/day, days 1–28) + C (1660 mg/m², days 1–21) or GE, q4 weeks, until progression or unacceptable toxicity. Primary end-point: progression-free survival (PFS); secondary end-points: overall survival (OS), response rate, relationship of rash with PFS/OS and safety.Results120 patients were randomised, median age 63 years, ECOG status 0/1/2 33%/58%/8%; median follow-up 16.5 months. Median PFS in the gemcitabine–erlotinib–capecitabine (GEC) and GE arms was 4.3 and 3.8 months, respectively (hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.58–1.31; p = 0.52). Median OS in the GEC and GE arms was 6.8 and 7.7 months, respectively (HR: 1.09, 95% CI: 0.72–1.63; p = 0.69). Grade 3/4 neutropenia (GEC 43% versus GE 15%; p = 0.0008) and mucositis (GEC 9% versus GE 0%; p = 0.03) were the only statistically significant differences in grade 3/4 adverse events. PFS and OS were significantly longer in patients with rash (grade ≥1) versus no rash (grade = 0): PFS 5.5 versus 2.0 months (HR = 0.39, 95% CI: 0.26–0.6; p < 0.0001) and OS: 9.5 versus 4.0 months (HR = 0.51, 95% CI: 0.33–0.77; p = 0.0014).ConclusionPFS with GEC was not significantly different to that with GE in patients with mPC. Skin rash strongly predicted erlotinib efficacy.The study was registered with ClinicalTrials.gov: NCT01303029.     

Pre- and postoperative prognostic factors for resectable esophageal adenocarcinoma

BackgroundPrognostication for esophageal cancer has traditionally relied on postoperative tissue specimens. This study aimed to use a histologically homogenous cohort to investigate the relationship between clinical, pathological or radiological variables and overall survival in patients undergoing esophagectomy for adenocarcinoma.MethodsA single-centre study of patients who underwent esophagectomy for adenocarcinoma over 10 years in a tertiary centre was performed. By regression analysis, variables available preoperatively and postoperatively were studied for prognostication. The primary outcome was overall survival.Results254 cases were analyzed. Over a median follow-up period of 31.8 months (IQR = 42.5), overall survival was 51.5 months (95% confidence interval: 33.0–69.9). According to hazard ratios (HR) for all-cause death, adverse prognostic factors included: a higher postoperative N-stage (HR ≥ 1.29; p ≤ 0.024), histopathological tumor length ≥25 mm (HR = 2.04; p = 0.03), poorer tumor differentiation (HR ≥ 2.86; p ≤ 0.042), and R1 status (HR = 2.33; p = 0.02). A lymph node yield ≥35 was a favorable prognostic factor (HR = 0.022; p < 0.001). Demographic and radiological variables, preoperative TNM stages, postoperative T-stage, and neoadjuvant/adjuvant treatment were not associated with overall survival.ConclusionsThis study identifies several postoperatively factors which are available for the prognostication and identifies factors that should not be used to exclude patients from curative surgery.     

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.     

Improved Overall Survival With Comprehensive Local Consolidative Therapy in Synchronous Oligometastatic Non–Small-Cell Lung Cancer

BackgroundLocal consolidative therapy (LCT) to optimize disease control is an evolving management paradigm in non–small-cell lung cancer (NSCLC) patients who present with a limited metastatic disease burden. We hypothesized that LCT to all sites of disease would be associated with improved overall survival (OS) among patients with synchronous oligometastatic NSCLC.Patients and MethodsPatients presenting to a single institution (2000-2017) with stage IV NSCLC and ≤ 3 synchronous metastases were identified. Intrathoracic nodal disease was counted as one site. Landmark and propensity-adjusted Cox regression analyses were performed to identify factors associated with OS.ResultsOf 194 patients, 143 (74%) had 2 or 3 sites of metastasis. LCT was delivered to all sites of disease in 121 patients (62%), to some but not all sites in 52 (27%), and were not used in 21 (11%). Comprehensive LCT was independently associated with improved OS (hazard ratio [HR] = 0.67; 95% confidence interval [CI], 0.46-0.97; P = .034), with the greatest therapeutic effect among patients without thoracic nodal disease, bone metastases, or > 1 metastatic site. Among patients who underwent comprehensive LCT, tumor histology (squamous: HR = 2.32; 95% CI, 1.28-4.22; P = .006), intrathoracic disease burden (T3-4: HR = 1.67; 95% CI, 0.97-2.86; P = .065; N3: HR = 1.90; 95% CI, 0.90-4.03; P = .093), and bone metastases (HR = 1.74; 95% CI, 1.02-3.00; P = .044) were associated with poor OS.ConclusionComprehensive LCT was associated with improved OS in this large cohort of patients with synchronous oligometastatic NSCLC. These results support ongoing prospective efforts to characterize the therapeutic benefits associated with this management strategy.     

Clinical management of adolescents and young adults suffering from sarcoma in the French Rhône-Alpes region: A prospective exhaustive cohort with 10 years follow up

IntroductionSurvival of adolescents and young adults (AYA) with sarcoma is lower than in younger patients. The objective of this study was to describe the regional healthcare circuits, the differences in the management between adult, paediatric and mixed units and to assess the prognostic impact of compliance with clinical practice guidelines (CPGs) on overall survival (OS) and on relapse free survival (RFS).Materials and methodsRetrospective analysis of the management and long term follow-up of all 13–25 year old patients with a sarcoma diagnosed in the Rhône-Alpes area between 2000 and 2005.Results140 patients satisfied inclusion criteria and were selected. The majority of 13–25 year old patients were treated in paediatric units. Joint management resulted in a higher rate of discussion in multidisciplinary tumour board, inclusion in clinical trials, and fertility preservation. Non-compliance with guidelines was observed in 65% of cases. Overall compliance was not reported to correlate to survival. Compliance of radiotherapy with CPG's seemed associated with a better prognosis for OS (HR = 0.20, 95% CI = [0.10–0.40]; p < 0.0001) and RFS (HR = 0.18, 95% CI = [0.09–0.37; p < 0.0001) as well as compliance of surgery for OS (HR = 0.43, 95% CI = [0.23–0.81]; p = 0.01). Multivariate Cox regression analysis revealed other independent predictors of OS like age at diagnosis, stage and histological subtype.ConclusionsManagement of AYA in joint units seems to improve the quality of care. Compliance of surgery and radiotherapy with CGP's seems to improve survival.     

Prognostic value of primary tumor sidedness in patients with non-metastatic IBD related CRC – Is it the exception to the rule?

BackgroundAlthough primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC.MethodsAll eligible patients with surgically treated, non-metastatic IBD-CRC were retrospectively identified from institutional databases at ten European and Asian academic centers. Long term endpoints included recurrence–free (RFS) and overall survival (OS). Multivariable Cox proportional hazard regression as well as propensity score analyses were performed to evaluate whether PTS was significantly associated with RFS and OS.ResultsA total of 213 patients were included in the analysis, of which 32.4% had right-sided (RS) tumors and 67.6% had left-sided (LS) tumors. PTS was not associated with OS and RFS even on univariable analysis (5-year OS for RS vs LS tumors was 68.0% vs 77.3%, respectively, p = 0.31; 5-year RFS for RS vs LS tumors was 62.8% vs 65.4%, respectively, p = 0.51). Similarly, PTS was not associated with OS and RFS on propensity score matched analysis (5-year OS for RS vs LS tumors was 82.9% vs 91.3%, p = 0.79; 5-year RFS for RS vs LS tumors was 85.1% vs 81.5%, p = 0.69). These results were maintained when OS and RFS were calculated in patients with RS vs LS tumors after excluding patients with rectal tumors (5-year OS for RS vs LS tumors was 68.0% vs 77.2%, respectively, p = 0.38; 5-year RFS for RS vs LS tumors was 62.8% vs 59.2%, respectively, p = 0.98).ConclusionsIn contrast to sporadic CRC, PTS does not appear to have a prognostic role in IBD-CRC.     

Rapid and objective CT scan prognostic scoring identifies metastatic patients with long-term clinical benefit on anti-PD-1/-L1 therapy

BackgroundDrugs targeting programmed death receptor-1 (PD-1) and its ligand PD-L1 have shown activity in multiple malignancies. Considering their novel mechanism of action, whether traditional prognostic scores also apply to patients treated with these drugs is unknown. We investigated whether a baseline 3-point (pt) computed tomography (CT) scan (PS3-CT) score and a 7-pt prognostic (PS7) score allowed identifying long-term survivors on anti-PD-1/-L1 therapy.Materials and methodsWe reviewed 251 consecutive patients enrolled in phase I trials evaluating anti-PD-1/-L1 agents between 26th December 2011 and 7th September 2015. PS3-CT was calculated using high tumour burden (TB_1D-RECIST > 9 cm), low skeletal muscle index (SMI < 53 cm² m⁻²) and non-pulmonary visceral metastases (NPVM) (1 pt each). PS7 was calculated by adding lower performance status, decreased serum albumin, increased serum lactate dehydrogenase and more than two distant metastases (1 pt each). Effect on overall survival (OS) of each parameter was tested using Kaplan–Meier and multivariable Cox analyses.ResultsPS3-CT was a significant independent predictor of OS (hazard ratio [HR] = 1.39 [95% confidence interval {CI} = 1.07–1.81], p = 0.01) when compared to the Royal Marsden Hospital, Barbot and American Joint Committee on Cancer scores. High TB (n = 78), low SMI (n = 55) and NPVM (n = 146) were associated with poorer survival (p < 0.01). High TB and low SMI were independent predictors of OS (respective HR of death: 2.00 [95% CI = 1.38–2.88], p < 0.01 and 1.75 [95% CI = 1.15–2.66], p < 0.01). PS7 was a significant predictor of OS (HR = 1.40 [95% CI = 1.25–1.56], p < 0.01).ConclusionObjective and rapid-risk scoring based on three CT scan parameters allows identifying patients with prolonged OS on anti-PD-1/-L1 therapy, independently from conventional clinical–biological prognostic scores.     

Prognostic Role of Low-Skeletal Muscle Mass on Staging Computed Tomography in Metastasized Colorectal Cancer: A Systematic Review and Meta-Analysis

BackgroundLow-skeletal muscle mass (LSMM) is defined as skeletal muscle loss, which can be assessed by imaging. Our aim was to establish the effect of LSMM on overall survival (OS) in metastasized colorectal cancer patients based on a large patient sample.Patients and MethodsMEDLINE library, EMBASE, and SCOPUS databases were screened for the associations between LSMM and mortality in metastasized colorectal cancer patients up to March 2022. The primary aim of the systematic review was to investigate the influence of LSMM on overall survival (OS) by means of the effect of measure hazard ratio. Fifteen studies were included into the present analysis.ResultsThe included studies comprised 1744 patients. The frequency of LSMM was 46.2%. Associations between LSMM and OS were as follows: hazard ratio (HR) = 1.34 (95% confidence interval [CI] 0.94-1.91), P = .10 in univariable analysis and HR = 2.05 (95% CI 1.18-3.56), P = .01 in multivariable analysis. LSMM influenced OS in patients undergoing first-line chemotherapy, HR = 1.51 (95% CI 1.20-1.89), P = .0004. In patients undergoing second- and third-line chemotherapy, LSMM was not associated with OS, HR = 1.43 (95% CI 0.65-3.14), P = .37 Also, LSMM did not affect OS in patients with resection of hepatic metastases, HR = 0.93 (95% CI 0.70-1.24), P = .63. LSMM tended to affect progression-free survival, HR = 1.49 (95% CI 0.94-2.35), P = .09. LSMM did not predict treatment toxicity, odds ratio (OR) = 1.52 (95% CI 0.84-2.72), P = .16.ConclusionLSMM occurs in 46.2% of patients with metastasized colorectal cancers. LSMM is associated with OS in patients undergoing first-line chemotherapy. LSMM does not affect OS in second- and third-line chemotherapy and in patients undergoing resection of hepatic metastases. LSMM is not associated with progression-free survival and treatment toxicity.     

Evaluation of radical surgical treatment in the management of 58 locally advanced rectal neuroendocrine neoplasms,one multicenter retrospective study

BackgroundLocally advanced rectal neuroendocrine neoplasms (NENs) are rare, and the therapeutic effects of surgery in improving the prognosis have been questioned in previous reports.Materials and methodsThe research included 58 consecutive patients with locally advanced rectal NENs from three Chinese medical centers between 2000 and 2020. All have received radical surgical treatment. The clinicopathological and survival data were collected. Kaplan-Meier methods and a Cox proportional hazards regression model were used to evaluate the prognosis and identify independent prognostic factors.ResultsAll patients were followed up for a median period of 36 (2–125) months. Of the 58 patients, 13 (22.4%) had G1 neuroendocrine tumors (NETs), 15 (25.9%) had G2 NETs, 6 (10.3%) had G3 NETs, and the remaining 24 (41.4%) patients had G3 neuroendocrine carcinomas (NECs). The 1-year and 3-year disease-free survival (DFS) rates were 64.5% and 48.8%, respectively. The 1-year and 3-year overall survival (OS) rates were 90.5% and 75.4%, respectively. Univariate analysis demonstrated that tumor differentiation (p = 0.002), gross morphology (p = 0.009), T stage (p = 0.024), and extramural vascular invasion (p = 0.009) were associated with the OS. The subsequent multivariate analysis confirmed that tumor differentiation [hazard ratio (HR) = 6.002, 95% confidence interval (CI): 1.210–29.767, p = 0.028] and gross morphology (HR = 3.438, 95% CI: 1.038–11.382, p = 0.043) were independent prognostic factors affecting the clinical outcomes.ConclusionsRectal NENs are a heterogeneous group of diseases. The survival benefits obtained from surgery vary widely based on the tumor clinicopathological features. Patients with G3 NECs and ulcerative mass are at high risks of poor prognosis.     

Surgical Prognosis of Synchronous Multiple Primary Lung Cancer: Systematic Review and Meta-Analysis

BackgroundWe evaluated the long-term prognosis of synchronous multiple primary lung cancer (SMPLC) patients after surgical treatment and explored prognostic factors for overall survival (OS).Materials and MethodsA systematic review and meta-analysis was performed regarding the surgical prognosis of SMPLC. A literature search was performed using online databases. All studies were rigorously categorized following the 8th edition of the tumor, node, metastasis classification (TNM) staging rules for multiple lung cancers: SMPLC and multifocal ground-glass/lepidic (GG/L) lung cancers. Five-year OS after surgery was pooled, and hazard ratios (HRs) for prognostic factors were synthesized. Specific subgroup analysis and sensitivity analysis were conducted (PROSPERO registration CRD42019142420).ResultsAn analysis of 26 studies including 1788 patients was performed. The pooled 5-year OS was 45% (95% confidence interval [CI], 37-53) of true SMPLC patients and 62% (95% CI, 57-67) of patients with pathologic stage I disease, which was different from the 5-year OS of 93% (95% CI, 85-100) of patients with multifocal GG/L lung cancers. Poor prognostic factors for SMPLC were lymph node metastasis (HR = 2.36; 95% CI, 1.75-3.20; P < .001) and pneumonectomy (HR = 2.96; 95% CI, 1.36-6.45; P = .006], whereas histology (HR = 1.11; 95% CI, 0.82-1.50; P = .508), laterality (HR = 1.16; 95% CI, 0.93-1.44, P = .190), sublobar resection (HR = 1.29; 95% CI, 0.90-1.84; P = .159), and adjuvant therapy (HR = 1.07; 95% CI, 0.64-1.80; P = .791) were not found to influence the outcome.ConclusionThe long-term prognosis of SMPLC patients after surgery is acceptable, especially in patients with early-stage disease. Sublobar resection can be applied, although pneumonectomy should be avoided. Advanced criteria are needed to diagnose SMPLC and distinguish it from multifocal GG/L lung cancer to perform accurate surgical evaluation.     

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.