Prognostic factors in patients with oligometastatic breast cancer – A systematic review

AimOligometastatic breast cancer (OMBC) is a disease-entity with potential for long-term remission in selected patients. Those with truly limited metastatic load (rather than occult widespread metastatic disease) may benefit from multimodality treatment including local ablative therapy of distant metastases. In this systematic review, we studied factors associated with long-term survival in patients with OMBC.MethodsEligible studies included patients with OMBC who received a combination of local and systemic therapy as multimodal approach and reported overall survival (OS) or progression-free survival (PFS), or both. The Quality in Prognosis Studies (QUIPS) tool was used to assess the quality of each included study. Independent prognostic factors for OS and/or PFS are summarized.ResultsOf 1271 screened abstracts, 317 papers were full-text screened and twenty studies were included. Eleven of twenty studies were classified as acceptable quality. Definition of OMBC varied between studies and mostly incorporated the number and/or location of metastases. The 5-year OS ranged between 30 and 79% and 5-year PFS ranged between 25 and 57%. Twelve studies evaluated prognostic factors for OS and/or PFS in multivariable models. A solitary metastasis, >24 months interval between primary tumor and OMBC, no or limited involved axillary lymph nodes at primary diagnosis, and hormone-receptor positivity were associated with better outcome. HER2-positivity was associated with worse outcome, but only few patients received anti-HER2 therapy.ConclusionsOMBC patients with a solitary distant metastasis and >24 months disease-free interval have the best OS and may be optimal candidates to consider a multidisciplinary approach.     

Comorbidities,timing of treatments,and chemotherapy use influence outcomes in stage III colon cancer: A population-based European study

IntroductionFor stage III colon cancer (CC), surgery followed by chemotherapy is the main curative approach, although optimum times between diagnosis and surgery, and surgery and chemotherapy, have not been established.Materials and methodsWe analysed a population-based sample of 1912 stage III CC cases diagnosed in eight European countries in 2009–2013 aiming to estimate: (i) odds of receiving postoperative chemotherapy, overall and within eight weeks of surgery; (ii) risks of death/relapse, according to treatment, Charlson Comorbidity Index, time from diagnosis to surgery for emergency and elective cases, and time from surgery to chemotherapy; and (iii) time-trends in chemotherapy use.ResultsOverall, 97% of cases received surgery and 65% postoperative chemotherapy, with 71% of these receiving chemotherapy within eight weeks of surgery. Risks of death and relapse were higher for cases starting chemotherapy with delay, but better than for cases not given chemotherapy. Fewer patients with high comorbidities received chemotherapy than those with low (P < 0.001). Chemotherapy timing did not vary (P = 0.250) between high and low comorbidity cases. Electively-operated cases with low comorbidities received surgery more promptly than high comorbidity cases. Risks of death and relapse were lower for elective cases given surgery after four weeks than cases given surgery within a week. High comorbidities were always independently associated with poorer outcomes. Chemotherapy use increased over time.ConclusionsOur data indicate that promptly-administered postoperative chemotherapy maximizes its benefit, and that careful assessment of comorbidities is important before treatment. The survival benefit associated with slightly delayed elective surgery deserves further investigation.     

Multidisciplinary treatment strategy for locally advanced gastric cancer: A systematic review

BackgroundMultidisciplinary management of patients with locally advanced gastric cancer (LAGC) remains unstandardized worldwide. We performed a systemic review to summarize the advancements, regional differences, and current recommended multidisciplinary treatment strategies for LAGC.MethodsEligible studies were identified through a comprehensive search of PubMed, Web of Science, Cochrane Library databases and Embase. Phase 3 randomized controlled trials which investigated survival of patients with LAGC who underwent gastrectomy with pre-/perioperative, postoperative chemotherapy, or chemoradiotherapy were included.ResultsIn total, we identified 11 studies of pre-/perioperative chemotherapy, 38 of postoperative chemotherapy, and 14 of chemoradiotherapy. In Europe and the USA, the current standard of care is perioperative chemotherapy for patients with LAGC using the regimen of 5-FU, folinic acid, oxaliplatin and docetaxel (FLOT). In Eastern Asia, upfront gastrectomy and postoperative chemotherapy is commonly used. The S-1 monotherapy or a regimen of capecitabine and oxaliplatin (CapOx) are used for patients with stage II disease, and the CapOx regimen or the S-1 plus docetaxel regimen are recommended for those with stage III Gastric cancer (GC). The addition of postoperative radiotherapy to peri- or postoperative chemotherapy is currently not recommended. Additionally, clinical trials testing targeted therapy and immunotherapy are increasingly performed worldwide.ConclusionsRecent clinical trials showed a survival benefit of peri-over postoperative chemotherapy and chemoradiotherapy. As such, this strategy may have a potential as a global standard for patients with LAGC. Outcome of the ongoing clinical trials is expected to establish the global standard of multidisciplinary treatment strategy in patients with LAGC.     

Laparoscopic versus open transhiatal approach for adenocarcinoma of the esophagogastric junction: A systematic review and meta-analysis

BackgroundThe incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide. Laparoscopic transhiatal approach (LTH) has gained growing popularity in the treatment of AEG. However, its safety and efficacy need to be evaluated.MethodsOriginal studies comparing LTH with open transhiatal approach (OTH) were searched. Meta-analysis was performed using RevMan 5.3.ResultsNine studies involving 2149 patients were eligible. Compared with OTH, LTH was associated with longer operation time (mean difference [MD] = 31min, 95%CI [20,41], P < 0.001) while less blood loss (MD = −103ml [-135, −72], P < 0.001), and harvested similar number of lymph nodes (MD = 0.1 [-1.2, 1.4], P = 0.89). There were no differences in time to ambulation (MD = −0.79 days [-1.77, 0.20], P = 0.12) or time to first flatus (MD = −0.82 days [-1.76, 0.11], P = 0.08); however, LTH was associated with shorter postoperative hospital stay (MD = −1.70 days [-2.34, −1.05], P < 0.001). The mortality after surgery was comparable for LTH and OTH (risk difference [RD] = -0.00 [-0.01, 0.01], P = 0.55). The incidence of total major complications was similar in LTH (6.1%) and OTH (8.4%) (RD = −0.02 [-0.05, 0.01], P = 0.12); there were no significant differences in the incidence of each complication. Furthermore, LTH achieved similar 2-year overall survival (OS) rate (risk ratio [RR] = 1.17 [0.86, 1.60], P = 0.31) while higher 5-year OS rate (RR = 1.43 [1.18, 1.73], P = 0.0003) and significant improvement of OS (univariable hazard ratio = 0.65 [0.50, 0.84], P = 0.0009; multivariable hazard ratio = 0.59 [0.44, 0.80], P = 0.0006).ConclusionsLTH is feasible and safe for AEG, and may provide more favorable short-term outcomes and potential long-term survival benefit, which needs to be confirmed by randomized trials.     

An Exploration of Trifluridine/Tipiracil Monotherapy and in Combination With Bevacizumab or Immune Checkpoint Inhibitors for Patients With Metastatic Colorectal Cancer: A Real-World Study

BackgroundTrifluridine/tipiracil (TAS-102) has achieved modest efficacy in the late-line treatment of metastatic colorectal cancer. The present study aimed to explore the clinical efficacy and drug toxicities of TAS-102 for patients with metastatic colorectal cancer in real-world clinical setting.MethodsFrom October 2020 to February 2022, patients with metastatic colorectal cancer who failed from 2 or more lines of prior therapy and treated with TAS-102 monotherapy, in combination with bevacizumab or immune checkpoint inhibitors (ICIs) were analyzed. The evaluation indicators were progression free survival (PFS), objective response rate , disease control rate (DCR), overall survival (OS) and drug toxicities.ResultsA total of 70 patients were enrolled. The objective response rate and DCR were 1.4% and 68.6%. The median PFS and OS were 6.0 (95% CI: 4.1-7.9) and 10.0 (95% CI: 8.3-11.7) months. Compared with TAS-102 monotherapy and TAS-102 plus ICIs, TAS-102 plus bevacizumab obtained superior DCR (75.9% vs. 50% vs. 40%, P = .047), PFS (6.3m vs. 3.0 m vs. 3.0 m, P = .041) and OS (12.0 m vs. 6.5 m vs. 6.0m, P = .013). Patients without prior regorafenib or fruquintinib therapy obtained better median PFS (6.3 vs. 4.3 m, P = .031) and OS (NR vs. 9.0 m, P = .036). Other indicators, including age, tumor site, KRAS status and use of fluoropyrimidine as last regimen before TAS-102, did not affect the clinical efficacy of TAS-102. The most frequent adverse events were leukopenia, neutropenia, anemia, fatigue, nausea, and vomiting.ConclusionIn real-world clinical setting, TAS-102 showed consistent clinical efficacy and manageable safety with previous prospective clinical studies. Compared with monotherapy and TAS-102 plus ICIs, TAS-102 plus bevacizumab demonstrated better clinical efficacy for metastatic colorectal cancer.     

Surgical treatment of pancreatic cancer: Currently debated topics on morbidity,mortality, and lymphadenectomy

This review will examine several aspects of pancreatic surgery. Over the past twenty years, the need for a standardized postoperative complication report after resective pancreatic surgery has led to the definition both of a postoperative complication severity score, a postoperative pancreatic fistula (POPF) severity grading, a fistula risk score (FRS) and a postoperative morbidity index to establish the burden of complications. Unfortunately, three problems have hindered the success of standardization: first, the failure to define a minimum postoperative follow-up period that needs to be reported; second, the lack of a clear definition of POPF-related morbidity and mortality; third, the often-incomplete reporting of postoperative complications. The debate on the extent of lymphadenectomy to associate to pancreaticoduodenectomy started in the late 1980s when, based on retrospective studies, Japanese surgeons reported better survival after extended” than after “standard” lymphadenectomy. Subsequently, eight prospective randomized controlled trials showed that “extended” lymphadenectomy offers no advantage over “standard” lymphadenectomy. Several consensus conference and reviews tried to define the optimal extent of lymphadenectomy to be associated to pancreaticoduodenectomy and distal pancreatectomy (DP). At least nineteen lymph nodes (LN) are required for optimal tumor staging, but eleven LN are considered the minimum to prevent under staging. There is no general agreement about aborting PD in LN16-positive patients; some authors perform PD in fit patients. Based on retrospective studies, a significant increase of R0 resections, a decrease of recurrence rate, a decrease of local recurrence rate and an increase of median or overall disease-free survival were reported after mesopancreas excision.     

A population-based study on incidence,treatment, and survival in ampullary cancer in the Netherlands

IntroductionAmpullary cancer is rare and as a result epidemiological data are scarce. The aim of this population-based study was to determine the trends in incidence, treatment and overall survival (OS) in patients with ampullary adenocarcinoma in the Netherlands between 1989 and 2016.MethodsPatients diagnosed with ampullary adenocarcinoma were identified from the Netherlands Cancer Registry. Incidence rates were age-adjusted to the European standard population. Trends in treatment and OS were studied over (7 years) period of diagnosis, using Kaplan-Meier and Cox regression analyses for OS and stratified by the presence of metastatic disease.ResultsIn total, 3840 patients with ampullary adenocarcinoma were diagnosed of whom, 55.0% were male and 87.1% had non-metastatic disease. The incidence increased from 0.59 per 100,000 in 1989–1995 to 0.68 per 100,000in 2010–2016. In non-metastatic disease, the resection rate increased from 49.5% in 1989–1995 to 63.9% in 2010–2016 (p < 0.001). The rate of adjuvant therapy increased from 3.1% to 7.9%. In non-metastatic disease, five-year OS (95% CI) increased from 19.8% (16.9–22.8) in 1989–1995 to 29.1% (26.0–31.2) in 2010–2016 (logrank p < 0.001). In patients with metastatic disease, median OS did not significantly improve (from 4.4 months (3.6–5.0) to 5.9 months (4.7–7.1); logrank p = 0.06). Cancer treatment was an independent prognostic factor for OS among all patients.ConclusionBoth incidence and OS of ampullary cancer increased from 1989 to 2016 which is most likely related to the observed increased resection rates and use of adjuvant therapy.     

Vinorelbine After Prior Treatment With Eribulin for Advanced Breast Cancer: A Single-Centre Experience Suggesting Cross-Resistance

IntroductionThe tubulin inhibitor, eribulin, improves survival for previously treated advanced breast cancer (ABC) compared to chemotherapy of physician's choice, including vinorelbine, an older anti-tubulin. Vinorelbine is commonly still used after eribulin, but potentially risks cross-resistance and its efficacy in this setting is unproven.Materials and MethodsA retrospective analysis of all patients who received vinorelbine after prior eribulin (VAE) 2011-2015 and a parallel cohort of consecutive patients who received vinorelbine without prior eribulin (VWE) for previously treated ABC between 2005 and 2011. Patient demographics, histopathological features, treatment duration and responses were recorded. The primary endpoint was progression-free survival from date of first vinorelbine for each cohort. Secondary endpoints included radiological response rate, and overall survival (OS).ResultsThirty-five VAE and 103 VWE patients were identified, all female, 71.4% and 78.6% were ER positive/HER2 negative, 8.6% and 6.8% HER2 positive, and 20.0% and 14.6% triple negative for VAE and VWE cohorts, respectively. The median number of lines of chemotherapy lines prior to vinorelbine was 4 (range 2-6) and 2 (range 0-4), respectively. Fifteen VAE patients (42.9%) received ≥1 line of chemotherapy between eribulin and vinorelbine. VAE and WWE Patients received a median of 3 cycles of vinorelbine (range 1-9 and 1-12, respectively). The median progression-free survival for VAE patients was 2.1 months and 2.0 months for VWE patients. No VAE patients were progression-free at 24 weeks, compared to 15.5% of VWE patients. Median OS from commencing vinorelbine was 4.3 months for VAE and 6.4 months for VWE patients.ConclusionVinorelbine was of limited benefit after prior eribulin in our study, suggesting cross-resistance. Even without prior eribulin, only 15% of patients experienced clinical benefit from vinorelbine monotherapy.     

A nationwide study on cancer recurrences,second primary tumours,distant metastases and survival after treatment for primary head and neck cancer in the Netherlands

IntroductionThere is no consensus on the optimal duration of post-treatment follow-up after head and neck cancer (HNC). To generate site-specific input for follow-up guidelines, this study describes the incidence and timing of manifestations of disease during five years of follow-up.MethodsAll patients diagnosed with HNC in the Netherlands in 2015 were selected from the Netherlands Cancer Registry. The follow-up events local recurrence (LR), regional recurrence (RR), second primary tumour (SPT), distant metastasis (DM) and death were studied per follow-up-year. The cumulative incidence of these events was calculated using competing risk analyses, with LR, RR and SPT of the head and neck (SPHNC) as events and SPT outside the head-neck (SPOHN), DM and death as competing events. Analyses were performed for oral cavity-, oropharynx-, larynx- and hypopharynx squamous cell carcinoma (SCC), and all HNC patients.ResultsThe 1-, 1.5-, and 2-year cumulative incidence of an event (LR, RR, SPHNC) were 10% (95%CI 8–13), 12% (95%CI 10–15), and 13% (95%CI 10–16) for oral cavity SCC; 6% (95%CI 4–9), 10% (95%CI 7–14), and 11% (95%CI 8–15) for oropharynx SCC; 7% (95%CI 5–10), 11% (95%CI 9–15), and 13% (95%CI 10–16) for larynx SCC and 11% (95%CI 6–19), 19% (95%CI 12–27), and 19% (95%CI 12–27) for hypopharynx SCC.ConclusionsOne year of follow-up for oral cavity SCC, and 1.5 years for oropharynx-, larynx-, and hypopharynx SCC suffices for the goal of detecting disease manifestations after treatment. More research into other aspects of follow-up care should be performed to determine the optimal follow-up regimen.     

CAR T-Cells for the Treatment of Refractory or Relapsed Large B-Cell Lymphoma: A Single-Center Retrospective Canadian Study

Background: Chimeric antigen receptor (CAR) T-cells are an important new third-line treatment option for large B-cell lymphoma (LBCL). The objective response rates in pivotal early phase clinical trials with CAR T-cells were very promising. The objective of this study was to describe the efficacy results obtained with CAR T-cells infusions in our institution and to compare the toxicities of our cohort with those of pivotal trials and studies conducted in a real-life setting.Patients and Methods: Efficacy and safety data were retrospectively collected from 25 patients with LBCL treated with CAR T-cells therapy at CHU de Québec-Université Laval. A literature search was then performed to identify other efficacy or safety data from a real-life setting. Results: At 3 months post infusion, the objective response rate (ORR) in our population with tisagenlecleucel and axicabtagene-ciloleucel were 20% and 47%, respectively. Bulky disease was the only negative predictor of poor response at 3 months (0% vs. 53%, P = .03). Bulky disease was associated with a median PFS of 2 months compared to 5 months for non-bulky disease (P = .0009). Grade ≥ 3 hematological toxicities were greater in patients treated with axi-cel (60% vs. 20%, P = .048), without bone marrow involvement (55% vs. 0%, P =.046), without stage IV disease (72% vs. 21%, P =.02), with refractory disease (67% vs. 10%, P =.01) or having been affected by cytokine release syndrome (58% vs. 0%, P =.02).Conclusion: The poor response rate at 3 months after infusion in our cohort was influenced mainly by bulky disease. Further studies are needed to better characterize the loss of efficacy of CAR T-cells because the majority of patients will relapse over time.     

Association of Apatinib and Breast Cancer: A systematic review and meta-analysis

BackgroundBreast cancer (BC) is a common malignant tumor. Apatinib in combination with other treatments has been used for BC; however, its safety and efficacy are not well-known. Therefore, this meta-analysis was performed to assess the efficacy and safety of apatinib in the treatment of BC.MethodsStudies comparing the effects of apatinib-based therapy versus control among BC patients were included. On January 21, 2022, a systematic search was performed in 9 databases. The risk ratio (RR) with 95% confidence interval (CI) was used to estimate efficacy and safety. The I square value (I²) was used to assess heterogeneity. A leave-one-out sensitivity analysis was also conducted. Publication bias was assessed by funnel plots and Egger's and Begg's tests.ResultsA total of 31 studies including 2,258 BC patients were included. The results showed that apatinib group had a significant improvement in disease control rate (DCR, RR = 1.43, 95% CI = 1.35–1.52, I² = 43.8%) and objective response rate (ORR, RR = 1.79, 95% CI = 1.51–2.13, I² = 61.8%) compared to the control group. Except for hemorrhage, hypertension, and hand-foot syndrome, the adverse events were similar between apatinib group and control group. Subgroup analyses found statistically significant differences in DCR in all subgroups except for apatinib combined with radiation therapy and with paclitaxel liposome plus S1. For ORR, there were statistically significant differences in all subgroups except for the radiation therapy, and apatinib monotherapy subgroups.ConclusionsOur study shown apatinib showed good efficacy and acceptable safety in the treatment of BC patients. More high-quality randomized controlled trials from different regions and countries are needed to confirm our findings.     

Impact of concurrent splenectomy and esophagogastric devascularization on surgical outcomes of partial hepatectomy for hepatocellular carcinoma in patients with clinically significant portal hypertension: A multicenter propensity score matching analysis

PurposePortal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED).Patients and methodsFrom a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM).ResultsOf the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9% vs. 36.5%, P = 0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4% vs. 21.7%, P = 0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P < 0.001).ConclusionHepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.     

Days alive and out of hospital after surgical treatment of epithelial ovarian cancer: A Danish nationwide cohort study

ObjectiveDays alive and out of hospital (DAOH) is a validated outcome measure in perioperative trials integrating information on primary hospitalization, readmissions, and mortality. It is negatively associated with advanced age. However, DAOH has not been described for surgical treatment of epithelial ovarian cancer (EOC), primarily diagnosed in older patients.MethodsWe conducted a Danish nationwide cohort study including patients undergoing debulking surgery for EOC from 2013 to 2018. DAOH was explored for 30 (DAOH30), 90 (DAOH90), and 180 (DAOH180) postoperative days in younger (<70 years) and older (≥70 years) patients with advanced-stage disease stratified by surgical modality (primary (PDS) or interval debulking surgery (IDS)). We examined the associations between patient- and surgical outcomes and low or high DAOH30.ResultsOverall, 1168 patients had stage IIIC-IV disease and underwent debulking surgery. DAOH30 was 22 days [interquartile range (IQR): 18, 25] and 23 days [IQR: 18, 25] for younger and older patients treated with PDS, respectively. For IDS, DAOH30 was 25 days [IQR: 22, 26] for younger and 25 days[IQR: 21, 26] for older patients. We found no significant differences between age cohorts regarding DAOH30, DAOH90, and DAOH180. Low DAOH30 was associated with poor performance status, PDS, extensive surgery, and long duration of surgery in adjusted analysis.ConclusionsDAOH did not differ significantly between age cohorts. Surgical rather than patient-related factors were associated with low DAOH30. Our results likely reflect a high selection of fit older patients for surgery, reducing the patient-related differences between younger and older patients receiving surgical treatment.     

Risk factors for late-onset lower limb lymphedema after gynecological cancer treatment: A multi-institutional retrospective study

IntroductionLate-onset lower limb lymphedema (LLL) is a significant clinical challenge for physicians dealing with patients that undergo treatment involving the pelvic cavity. We aimed to clarify the prevalence of and risk factors for late-onset LLL after treatment for gynecological cancer.MethodsWe conducted a multicenter retrospective study using records of cases in which LLL diagnosed by physical findings and measurement of limbs girths. Patients with LLL after treatment for uterine cervical, endometrial, and ovarian cancer were sequentially enrolled. We examined the timing of LLL onset and the associations between the time to onset and clinical characteristics, including age, type of cancer, lymphadenectomy sites, and performance of radiotherapy. We also investigated the risk factors for late-onset LLL and their effects on the cumulative incidence of late-onset LLL.ResultsIn total, 711 patients fulfilled the required criteria. Mean age of was 50.2 years old and median follow-up period was 5.05 years. More than half of them (50.5%) presented with LLL ≥5 years after undergoing treatment for gynecological cancer. A substantial number of patients (29.4%) developed LLL ≥10 years after undergoing treatment for gynecological cancer. Being aged <50 years [(odds ratio (OR): 1.919, P = 0.001), cervical cancer (OR: 1.912, P = 0.001), and radiotherapy (OR: 1.664, P = 0.017) were identified as significant risk factors for late-onset LLL in multivariate logistic regression analysis.ConclusionsA substantial number of patients present with LLL ≥5 years after receiving treatment for gynecological malignancies. Clinicians are required to identify high-risk patients and inform them of the risk of late-onset LLL.     

The effect of the American Joint Committee on Cancer eighth edition on breast cancer staging and prognostication

IntroductionBreast cancer staging has been developed to quantify prognosis and guide treatment. The American Joint Committee on Cancer eighth edition manual (AJCC8) departed from traditional anatomic staging by incorporating biological factors such as grade, hormone and HER2 receptor status into a novel prognostic staging model. The aim of this study was to externally validate AJCC8 prognostic staging.MethodsThis retrospective cohort investigated patients diagnosed between 2010 and 2013 at the McGill University Health Center. Patients were classified using both anatomic and prognostic staging systems according AJCC8. Overall survival analysis using a multivariate Cox-proportional hazard model was performed and model accuracy was evaluated using the Harrell concordance index (C-index) and Akaike Information Criterion (AIC).ResultsThe cohort included 1703 women. Anatomic and prognostic stage assignments displayed discrepancies for 46.2% of patients, where 38.8% were downstaged and 7.5% were upstaged with prognostic staging. Patients with anatomic stages IB, IIA, IIB, IIIA and IIIC had high rates of downstaging (64.6–96.5%), as opposed to anatomic stages IA and IIIB where 93.1% and 75.0% of patients stage remained unchanged, respectively. The prognostic stage displayed increased prognostic accuracy with respect to overall survival, where the C-index was significantly higher compared to anatomic staging (0.810 vs 0.799, p < 0.05). In addition, prognostic staging displayed an improved model fit with a lower AIC (983.9) compared to anatomic staging (995.2).ConclusionPrognostic and anatomic staging differ in their classification of patients, where prognostic staging displays improved accuracy, supporting its use in informing patient prognosis and guiding treatment decisions.     

Technical,functional, and oncological validity of robot-assisted total-intersphincteric resection (T-ISR) for lower rectal cancer

BackgroundFew studies fairly compared anorectal function and prognostic outcomes between patients undergoing abdominoperineal resection (APR) and anorectal-function-saving operations (ASO) under the equivalent conditions. By contrast, surgeons used to be somewhat hesitant to conduct total intersphincteric resection (T-ISR) as maximal ASO, due to its technical complexity and potential anorectal dysfunction.MethodsPropensity-score matched cohorts undergoing robot-assisted R0 surgery [T-ISR vs APR vs partial-subtotal ISR (PS-ISR)/lower anterior resection (LAR)] for rectal cancer (n = 1361) were included. Operative outcomes, recurrence, and disease-free/overall survival (DFS/OS) were analyzed. Anorectal function was evaluated based on fecal incontinence score and high-resolution manometry between the T-ISR and other ASO groups.ResultsFew differences were detected between the T-ISR and APR groups. More patients undergoing APR had T4 stage disease, while the lowest tumor margin was the same in both groups (mean, 1.5 cm from anal verge). Prognostic outcomes did not differ between the T-ISR and APR groups, including local (5.1% vs 7.7%, p = 1) or systemic (15.4% vs 25.6%, p = 0.401) recurrence, and 5-year DFS (78.7% vs 61.5%, p = 0.1) and OS (89% vs 82.1%, p = 0.434) rates, nor were there differences between the T-ISR and PS-ISR/LAR groups. The PS-ISR group generally showed less anorectal dysfunction than the T-ISR group, but maximal tolerance volume did not differ between these two groups and was within the range for the healthy population.ConclusionsT-ISR can replace most traditional APR, except for advanced T4 disease with aggressive infiltration into the levator-sphincters, and can provide tolerable anorectal dysfunction.     

Perioperative nutritional assessment and interventions in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC): A systematic review

BackgroundPeritoneal carcinomatosis is a catabolic state and cytoreductive surgery (CRS) is a high morbidity operation. Optimising perioperative nutrition is crucial to improve outcomes. This systematic review sought to examine literature describing clinical outcomes related to preoperative nutrition status and nutrition interventions in patients undergoing CRS with hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsA systematic review was registered with PROSPERO (300326). A search of eight electronic databases was undertaken on 8th May 2022 and reported according to the PRISMA statement. Studies reporting nutrition status through use of screening and assessment tools, nutrition interventions or nutrition-related clinical outcomes for patients undergoing CRS with HIPEC were included.ResultsOf 276 screened studies, 25 studies were included for review. Commonly used nutrition assessment tools for CRS-HIPEC patients included Subjective Global Assessment (SGA), sarcopenia assessment with computed tomography, preoperative albumin, and body mass index (BMI). Three retrospective studies compared SGA with postoperative outcomes. Malnourished patients were more likely to have postoperative infectious complications (p = 0.042 SGA-B, p = 0.025 SGA-C). Malnutrition was significantly associated with increased hospital length of stay (LOS) in two studies (p = 0.006, p = 0.02), and with overall survival in another study (p = 0.006). Eight studies analysing preoperative albumin levels reported conflicting associations with postoperative outcomes. BMI in five studies was not associated with morbidity. One study did not support routine nasogastric tube (NGT) feeding.ConclusionsPreoperative nutritional assessment tools, including SGA and objective sarcopaenia measures, have a role in predicting nutritional status for CRS-HIPEC patients. Optimisation of nutrition is important for preventing complications.     

The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R): Real-World Data on Stage III Non-Small Cell Lung Cancer Patients Treated With Curative Chemoradiation

IntroductionChemoradiotherapy (CRT) is the standard of care in inoperable non–small-cell lung cancer (NSCLC) patients, favoring concurrent (cCRT) over sequential CRT (seqCRT), with adjuvant immunotherapy in responders. Elderly and frail NSCLC patients have generally been excluded from trials in the past. In elderly patients however, the higher treatment related morbidity of cCRT, may outweigh the possible lower tumor control of seqCRT. For elderly patients with locally advanced NSCLC real-world data is essential to be able to balance treatment toxicity and treatment outcome. The aim of this study is to analyze acute toxicity and 3-month mortality of curative chemoradiation (CRT) in patients with stage III NSCLC and to analyze whether cCRT for elderly stage III NSCLC patients is safe.MethodsThe Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) is a national lung cancer audit that started in 2013 for patients treated with curative intent radiotherapy. All Dutch patients treated for stage III NSCLC between 2015 and 2018 with seqCRT or cCRT for (primary or recurrent) stage III lung cancer are included in this population-based study. Information was collected on patient, tumor- and treatment characteristics and the incidence and severity of acute non-hematological toxicity (CTCAE-4 version 4.03) and mortality within 3 months after the end of radiotherapy. To evaluate the association between prognostic factors and outcome (acute toxicity and mortality within 3 months), an univariable and multivariable analysis was performed. The definition of cCRT was:radiotherapy started within 30 days after the start of chemotherapy.ResultsOut of all 20 Dutch departments of radiation oncology, 19 centers participated in the registry. A total of 2942 NSCLC stage III patients were treated with CRT. Of these 67.2% (n = 1977) were treated with cCRT (median age 66 years) and 32.8% (n = 965) were treated with seqCRT (median age 69 years). Good performance status (WHO 0-1) was scored in 88.6% for patients treated with cCRT and in 71.0% in the patients treated with seqCRT. Acute nonhematological 3-month toxicity (CTCAE grade ≥3 or radiation pneumonitis grade ≥2) was scored in 21.9% of the patients treated with cCRT and in 17.7% of the patients treated with seqCRT. The univariable analysis for acute toxicity showed significantly increased toxicity for cCRT (P = .008), WHO ≥2 (P = .006), and TNM IIIC (P = .031). The multivariable analysis for acute toxicity was significant for cCRT (P = .015), WHO ≥2 (P = .001) and TNM IIIC (P = .016). The univariable analysis for 3-month mortality showed significance for seqCRT (P = .025), WHO ≥2 (P < .001), higher cumulative radiotherapy dose (P < .001), higher gross tumor volume total (P = .020) and male patients (p < .001). None of these variables reached significance in the multivariable analysis for 3-month mortality.ConclusionIn this national lung cancer audit of inoperable NSCLC patients, 3-month toxicity was significantly higher in patients treated with cCRT (21.9% vs. 17.7% for seqCRT) higher TNM stage IIIC, and poor performance (WHO≥2) patients.The 3-months mortality was not significantly different for tested parameters. Age was not a risk factor for acute toxicity, nor 3 months mortality.