New Frontiers in Pancreatic Cancer Management: Current Treatment Options and the Emerging Role of Neoadjuvant Therapy.

Pancreatic ductal adenocarcinoma (PDAC) ranks among the 15 most prevalent cancers globally, characterized by aggressive growth and late-stage diagnosis. Advances in imaging and surgical techniques have redefined the classification of pancreatic PDAC into resectable, borderline resectable, and locally advanced pancreatic cancer. While surgery remains the most effective treatment, only 20% of patients are eligible at diagnosis, necessitating innovative strategies to improve outcomes. Therefore, traditional treatment paradigms, primarily surgical resection for eligible patients, are increasingly supplemented by neoadjuvant therapies (NAT), which include chemotherapy, radiotherapy, or a combination of both. By administering systemic therapy prior to surgery, NAT aims to reduce tumor size and increase the feasibility of complete surgical resection, thus enhancing overall survival rates and potentially allowing more patients to undergo curative surgeries. Recent advances in treatment protocols, such as FOLFIRINOX and gemcitabine-nab-paclitaxel, now integral to NAT strategies, have shown promising results in increasing the proportion of patients eligible for surgery by effectively reducing tumor size and addressing micrometastatic disease. Additionally, they offer improved response rates and survival benefits compared to traditional regimes. Despite these advancements, the role of NAT continues to evolve, necessitating ongoing research to optimize treatment regimens, minimize adverse effects, and identify patient populations that would benefit most from these approaches. Through a detailed analysis of current literature and recent clinical trials, this review highlights the transformative potential of NAT in managing PDAC, especially in patients with borderline resectable or locally advanced stages, promising a shift towards more personalized and effective management strategies for PDAC.

International Recommendations on Postoperative Management for Potentially Resectable Locally Recurrent Nasopharyngeal Carcinoma.

PURPOSE: Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. While postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. METHODS AND MATERIALS: A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. RESULTS: The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60Gy, and hyperfractionation has shown promise in reducing toxicity. CONCLUSION: These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for the clinical experts involved in the treatment of locally recurrent NPC. SUMMARY: This article provides international recommendations on postoperative management for potentially resectable locally recurrent nasopharyngeal carcinoma (NPC), with a special focus on postoperative re-irradiation (re-RT). The consensus guidelines highlight the importance of achieving clear surgical margins, suggest considering re-RT for patients with positive or close margins, recommend an optimal re-RT dose of around 60Gy, and propose the use of hyperfractionation to reduce toxicity. The aim is to improve patient outcomes in the management of resectable locally recurrent NPC.

Reappraisal of the current resectability criteria and optimal treatment strategies for pancreatic cancer.

Background: Recent advances in anticancer treatment and prolonged survival are the background of this study. The study aimed to reappraise the Japan Pancreas Society (JPS) resectability criteria in pancreatic cancer and to propose optimal treatment strategies. Methods: Three hundred ninety-six consecutive patients with curative-intent surgery for pancreatic cancer from April 2011 to December 2022 were included. Overall survival based on the resectability criteria was analyzed, and Cox regression analyses were performed to identify factors associated with overall survival. Results: The median survival times (MSTs) based on the current resectability status were 37.4, 20.1, and 26.6 months in resectable (R), in borderline resectable (BR), and unresectable (UR) disease, respectively (P<0.001), revealing an inversion phenomenon between BR and UR. Using the International Association of Pancreatology (IAP) criteria, the MST of biological BR disease was demonstrably worse than that of R disease (27.1 vs. 40.7 months, P=0.04), but no difference was observed between classical BR and UR locally advanced disease (18.8 vs. 18.7 months, P=0.97). Rather, ≤180° superior mesenteric artery (SMA) invasion was a more powerful prognostic factor than >180° SMA/celiac artery invasion in multivariate analysis (hazard ratio: 2.101, 95% confidence interval: 1.296-3.404, P=0.003). When biological BR was combined with BR, and BR with artery invasion was considered locally advanced disease as a new resectability criterion, the MSTs were 38.8, 23.5, and 18.5 months in the new R, new BR, and locally advanced groups, respectively (P<0.001). Conclusions: The decision-making and treatment strategies based on our new classification in pancreatic cancer are considered reasonable for clinical practice.

Role of thoracic endovascular aortic repair in T4b esophageal cancer management: a systematic review.

The incidence of T4b esophageal cancer with aortic invasion but without distant metastasis is estimated to be between 3.8% and 4.6% of all esophageal cancer cases. Development of an aortoesophageal fistula in such cases is a rare but not unlikely event, leading to catastrophic consequences. The aim of this systematic review is to evaluate the importance of aortic stenting (Thoracic Endovascular Aortic Repair-TEVAR) and its optimal timing in the management of locally advanced esophageal cancer. A systematic literature search of the MEDLINE, Scopus, and Google Scholar databases was undertaken to identify relevant studies published up to March 2024. An individual patient data analysis was performed by forming a patient cohort with elective and salvage TEVAR subgroups, depending on the timing of the stenting. The study pool consisted of 25 studies incorporating 101 cases of locally advanced esophageal cancer, with a median age of 64 years (range 45-87 years). Of them, 50 patients underwent elective TEVAR compared with 51 patients receiving TEVAR in an acute salvage setting. Elective or prophylactic TEVAR was found to significantly increase esophageal resection rates (65.6% vs. 16.7% in the salvage subgroup, P < 0.001), concurrently reducing complication rates (8.3% vs. 36.1%, P < 0.001). Overall survival was also prolonged in the elective subgroup (8.3 vs. 4 months, P = 0.001), with elective stenting being the only independent predictor of improved survival. In conclusion, management with aortic stenting in high-risk patients may reduce the catastrophic consequences of massive bleeding, minimize complications, and enhance survival rates.

Surgical management of pancreatic neuroendocrine tumors - An EYSAC and E-AHPBA international survey of current practice.

INTRODUCTION: Pancreatic neuroendocrine tumors (pNET) exhibit a wide spectrum of clinical behavior, which makes their assessment and management quite challenging. The purpose of this study was to comprehensively assess the existing treatment landscape for patients with pNET. MATERIALS AND METHODS: The study was conducted with the support of the ESSO-EYSAC Research Academy in collaboration with the E-AHPBA. An online survey was distributed via email and social media to surgical networks across Europe and beyond (September 1-30, 2023). RESULTS: Overall, 155 complete responses were obtained. A specialized NET tumor board was present at the institutions of 94 (61 %) of the study participants. The most frequently applied guidelines were from ENETS (n = 97; 63 %), NCCN (n = 74; 48 %), and ESMO (n = 53; 34 %). For resectability, similar criteria as in pancreatic ductal adenocarcinoma were used by 111 (72 %) participants, even though 116 (75 %) participants believed that pNET/pNEC should have their own resectability criteria. Most respondents used somatostatin analogues (n = 126; 81 %) and chemotherapy (n = 85; 55 %) as neoadjuvant treatments, followed by molecularly targeted agents (n = 45; 29 %) and PRRT (n = 37; 24 %). Only 17 (11 %) participants agreed/strongly agreed that the management of pNET/pNEC is sufficiently addressed in surgical education programs. CONCLUSION: This international survey highlighted areas for improvement in the care of pNET, namely the lack of pNET-specific resectability criteria and educational programs addressing pNET management.

SCANPatient: study protocol for a multi-centre, batched, stepped wedge, comparative effectiveness, randomised clinical trial of synoptic reporting of computerised tomography (CT) scans assessing cancers of the pancreas.

BACKGROUND: Complete surgical removal of pancreatic ductal adenocarcinoma (PDAC) is central to all curative treatment approaches for this aggressive disease, yet this is only possible in patients technically amenable to resection. Hence, an accurate assessment of whether patients are suitable for surgery is of paramount importance. The SCANPatient trial aims to test whether implementing a structured synoptic radiological report results in increased institutional accuracy in defining surgical resectability of non-metastatic PDAC. METHODS: SCANPatient is a batched, stepped wedge, comparative effectiveness, cluster randomised clinical trial. The trial will be conducted at 33 Australian hospitals all of which hold regular multi-disciplinary team meetings (MDMs) to discuss newly diagnosed patients with PDAC. Each site is required to manage a minimum of 20 patients per year (across all stages). Hospitals will be randomised to begin synoptic reporting within a batched, stepped wedge design. Initially all hospitals will continue to use their current reporting method; within each batch, after each 6-month period, a randomly selected group of hospitals will commence using the synoptic reports, until all hospitals are using synoptic reporting. Each hospital will provide data from patients who (i) are aged 18 or older; (ii) have suspected PDAC and have an abdominal CT scan, and (iii) are presented at a participating MDM. Non-metastatic patients will be documented as one of the following categories: (1) locally advanced and surgically unresectable; (2) borderline resectable; or (3) anatomically clearly resectable (Note: Metastatic disease is treated as a separate category). Data collection will last for 36 months in each batch, and a total of 2400 patients will be included. DISCUSSION: Better classifying patients with non-metastatic PDAC as having tumours that are either clearly resectable, borderline or locally advanced and unresectable may improve patient outcomes by optimising care and treatment planning. The borderline resectable group are a small but important cohort in whom surgery with curative intent may be considered; however, inconsistencies with definitions and an understanding of resectability status means these patients are often incorrectly classified and hence overlooked for curative options. TRIAL REGISTRATION: The SCANPatient trial was registered on 17th May 2023 in the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12623000508673).

The Role of Neoadjuvant and Adjuvant Chemotherapy in Pancreatic Cancer.

Pancreatic cancer is an aggressive malignancy. Recurrences are very high despite high-quality surgery necessitating adjuvant therapy. The evolution of adjuvant therapy took several decades and gradually evolved from single-agent chemotherapy to multi-agent chemotherapy. The two important agents that are active in pancreatic cancer are 5-fluorouracil and gemcitabine, and with several combinations showing better results in the subsequent trials, the most recent trial PRODIGE 24 shows a median survival of 54.4 months. The role of neoadjuvant therapy is still evolving in resectable cancers. The role of adjuvant radiotherapy is not well defined due to controversial results from historical trials.

Outcomes of chemotherapy/chemoradiation vs. R2 surgical debulking vs. palliative care in nonresectable locally recurrent rectal cancer.

Locally recurrent rectal cancer is resected with clear margins in only 50% of cases, and these patients achieve a three-year survival rate of 50%. Outcomes and therapeutic strategies for nonresectable locally recurrent rectal cancer have been much less explored. The aim of the study was to assess the three-year progression-free survival and the three-year overall survival in locally recurrent rectal cancer patients treated by chemotherapy/chemoradiation only vs. chemotherapy/chemoradiation and R2 surgical debulking vs. palliative care. A total of 86 patients affected by nonresectable locally recurrent rectal cancer were included: three-year progression-free survival was 15.8% with chemotherapy/chemoradiation vs. 20.3% with R2 surgical debulking (Log-rank p=0.567), but both rates were higher than best palliative care (0.0%, Log-rank p=0.0004). Three-year overall survival rates were respectively 62.0%, 70.8% and 0.0% (Log-rank p<0.0001). Chemotherapy/chemoradiation (HR 0.33, p=0.028) and R2 surgical debulking with or without chemotherapy/chemoradiation (HR 0.23, p=0.005) were independent predictors of improved progression-free survival on multivariate analysis. In conclusion, both chemotherapy/chemoradiation alone and R2 surgery with or without chemotherapy/chemoradiation provide a survival benefit over palliative care in nonresectable locally recurrent rectal cancer. However, considering that pelvic debulking is burdened by a high rate of complications, and considering its negligible impact on progression-free survival and overall survival when associated to medical therapy, surgery should be avoided in this setting.

Treatment patterns and clinical outcomes of resectable clinical stage III non-small cell lung cancer in a Japanese real-world setting: Surgery cohort analysis of the SOLUTION study.

BACKGROUND: To elucidate the treatment and surgery outcomes with or without perioperative therapies in Japanese patients with clinical stage III non-small cell lung cancer (NSCLC) in real-world settings. METHODS: We performed subset analyses of the SOLUTION study, a multicenter, noninterventional, observational study of Japanese patients diagnosed with clinical stage III NSCLC, for those who started first-line treatment (surgery±perioperative therapy) between January 2013 and December 2014 (study registration: UMIN000031385). Follow-up data were obtained using medical records from diagnosis to March 1, 2018. RESULTS: Of 149 eligible patients, 67 underwent surgery alone (median age 71 years) and 82 underwent surgery+perioperative therapy (median age 63 years). Lung resection was performed in 137 patients and the others underwent exploratory thoracotomy or other procedures. Perioperative therapies included adjuvant therapy only (n = 41), neoadjuvant therapy only (n = 24), and neoadjuvant+adjuvant therapy (n = 17). The median overall survival (OS) and 3-year OS rate were 29.3 months and 44.0%, respectively, in patients who underwent surgery alone, and not reached and 61.1%, respectively, in patients who underwent surgery+perioperative therapy. The 3-year progression-free survival (PFS) and disease-free survival (DFS) rates were 42.4% and 47.1%, respectively, in patients who underwent surgery+perioperative therapy and 28.5% and 28.9%, respectively, in patients who underwent surgery alone. In multivariable Cox regression, perioperative therapy was associated with improved OS (hazard ratio [95% confidence interval] 0.49 [0.29-0.81]), PFS (0.62 [0.39-0.96]), and DFS (0.62 [0.39-0.97]) versus surgery alone. CONCLUSIONS: Our study suggested that perioperative therapy may be associated with better survival among patients undergoing surgical treatment of clinical stage III NSCLC.

Preoperative CA19­9 level and dual time point FDG­PET/CT as strong biological indicators of borderline resectability in pancreatic cancer: A retrospective study.

Tumor resectability, which is increasingly determined based on preoperative chemotherapy, is critical in determining the best treatment for pancreatic cancers. The present study evaluated the usefulness of serum carbohydrate antigen 19-9 (CA19-9) and the preoperative 8F-fluorodeoxyglucose positron emission tomography/computed tomography standardized uptake value (SUV) percentage change (SUVmax%=[(SUVmax2-SUVmax1)/SUVmax1] ×100, where SUVmax1 and SUVmax2 represent the initial and delayed phases, respectively) as biological factors indicative of tumor resectability. The present study included patients with resectable pancreatic cancer who underwent complete surgical resection, for whom both CA19-9 and SUVmax% were documented using cut-off values of 500 U/ml and 24.25%, respectively. Patients were classified as follows: i) High CA19-9 and SUVmax%: both CA19-9 and SUVmax% were elevated; ii) high CA19-9 or SUVmax%: either CA19-9 or SUVmax% were elevated; or iii) low CA19-9 and SUVmax%: neither value met the cut-off. Relapse-free survival (RFS) and overall survival (OS) were calculated, for which univariate and multivariate analyses were performed. Of the 86 patients included, 39 were classified as high CA19-9 or SUVmax% and 12 as high CA19-9 and SUVmax%, with the former group having a significantly worse RFS (vs. low CA19-9 and SUVmax%; P<0.001; vs. high CA19-9 or SUVmax%; P=0.011) and OS (vs. low CA19-9 and SUVmax%, P=0.002; vs. high CA19-9 or SUVmax%, P<0.001). Therefore, high CA19-9 and SUVmax% was an independent predictor of worse RFS (P<0.001) and OS (P=0.003). In conclusion, CA19-9 and SUVmax% can be utilized as biological indicators of resectability.

Inter-reader agreement of pancreatic adenocarcinoma resectability assessment with photon counting versus energy integrating detector CT.

PURPOSE: To compare the inter-reader agreement of pancreatic adenocarcinoma resectability assessment at pancreatic protocol photon-counting CT (PCCT) with conventional energy-integrating detector CT (EID-CT). METHODS: A retrospective single institution database search identified all contrast-enhanced pancreatic mass protocol abdominal CT performed at an outpatient facility with both a PCCT and EID-CT from 4/11/2022 to 10/30/2022. Patients without pancreatic adenocarcinoma were excluded. Four fellowship-trained abdominal radiologists, blinded to CT type, independently assessed vascular tumor involvement (uninvolved, abuts ≤ 180°, encases > 180°; celiac, superior mesenteric artery (SMA), common hepatic artery (CHA), superior mesenteric vein (SMV), main portal vein), the presence/absence of metastases, overall tumor resectability (resectable, borderline resectable, locally advanced, metastatic), and diagnostic confidence. Fleiss's kappa was used to calculate inter-reader agreement. CTDIvol was recorded. Radiation dose metrics were compared with a two-sample t-test. A p < .05 indicated statistical significance. RESULTS: 145 patients (71 men, mean[SD] age: 66[9] years) were included. There was substantial inter-reader agreement, for celiac artery, SMA, and SMV involvement at PCCT (kappa = 0.61-0.69) versus moderate agreement at EID-CT (kappa = 0.56-0.59). CHA had substantial inter-reader agreement at both PCCT (kappa = 0.67) and EIDCT (kappa = 0.70). For metastasis identification, radiologists had substantial inter-reader agreement at PCCT (kappa = 0.78) versus moderate agreement at EID-CT (kappa = 0.56). CTDIvol for PCCT and EID-CT were 16.9[7.4]mGy and 29.8[26.6]mGy, respectively (p < .001). CONCLUSION: There was substantial inter-reader agreement for involvement of 4/5 major peripancreatic vessels (celiac artery, SMA, CHA, and SMV) at PCCT compared with 2/5 for EID-CT. PCCT also afforded substantial inter-reader agreement for metastasis detection versus moderate agreement at EID-CT with statistically significant radiation dose reduction.

Surgery for Oligometastatic Pancreatic Cancer: Defining Biologic Resectability.

Pancreatic ductal adenocarcinoma (PDAC) is most often metastatic at diagnosis. As systemic therapy continues to improve alongside advanced surgical techniques, the focus has shifted toward defining biologic, rather than technical, resectability. Several centers have reported metastasectomy for oligometastatic PDAC, yet the indications and potential benefits remain unclear. In this review, we attempt to define oligometastatic disease in PDAC and to explore the rationale for metastasectomy. We evaluate the existing evidence for metastasectomy in liver, peritoneum, and lung individually, assessing the safety and oncologic outcomes for each. Furthermore, we explore contemporary biomarkers of biological resectability in oligometastatic PDAC, including radiographic findings, biochemical markers (such as CA 19-9 and CEA), inflammatory markers (including neutrophil-to-lymphocyte ratio, C-reactive protein, and scoring indices), and liquid biopsy techniques. With careful consideration of existing data, we explore the concept of biologic resectability in guiding patient selection for metastasectomy in PDAC.

Advances in Surgery and (Neo) Adjuvant Therapy in the Management of Pancreatic Cancer.

A multimodality approach, which usually includes chemotherapy, surgery, and/or radiotherapy, is optimal for patients with localized pancreatic cancer. The timing and sequence of these interventions depend on anatomic resectability and the biological suitability of the tumor and the patient. Tumors with vascular involvement (ie, borderline resectable/locally advanced) require surgical reassessments after therapy and participation of surgeons familiar with advanced techniques. When indicated, venous reconstruction should be offered as standard of care because it has acceptable morbidity. Morbidity and mortality of pancreas surgery may be mitigated when surgery is performed at high-volume centers.

A Podcast on Pre- or Perioperative Chemoimmunotherapy for Stage III Non-Small Cell Lung Cancer: Shared Agreement from the Thoracic Surgeon and Oncologist Perspectives.

Management of stage II-III non-small cell lung cancer (NSCLC) has been dramatically revolutionized by studies testing the addition of immunotherapy (IO) to chemotherapy in the pre- or perioperative setting. That is because the integration of chemoimmunotherapy (chemo-IO) with surgery has consistently shown a significant improvement in pathological complete response (path CR) rate, event-free survival, and, more recently, overall survival, versus preoperative chemotherapy alone. Particularly, resectable stage III NSCLCs represent a disease entity with a high risk of distant recurrence after radical surgery, for whom pre- or perioperative chemo-IO should be considered as the preferential treatment option. However, owing to the heterogeneity of stage III NSCLC, a standard definition of resectability is not established yet, being often subjective according to the expertise and clinical background of the thoracic surgeon. In addition, careful patient selection on the basis of tumor biomarkers, meticulous staging of the disease, and accurate monitoring of treatment-related adverse events are critical factors that could prevent the ineligibility for surgery of patients treated with pre- or perioperative chemo-IO. Finally, the impact of downstaging for initially borderline resectable tumors, as well as the exact number of preoperative chemo-IO cycles needed and the indications for adjuvant IO, still need to be fully elucidated. In this podcast, we will touch upon the above-mentioned topics from the perspectives of the thoracic surgeon and the oncologist, and suggest a shared agreement between two of the main actors involved in the treatment of resectable stage III NSCLCs.Podcast audio available for this publication.

Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis.

Colorectal cancer liver metastasis (CRLM) presents a clinical challenge, and optimizing treatment strategies is crucial for improving patient outcomes. Surgical resection, a key element in achieving prolonged survival, is often linked to a heightened risk of recurrence. Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases, this approach has gained attention for its role in tumor downsizing, assessing biological behavior, and reducing the risk of postoperative recurrence. However, the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates. The balance between tumor reduction and the risk of hepatic injury, coupled with concerns about delaying surgery, necessitates a nuanced approach. This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases. Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion. Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative. The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing, such as RAS/BRAF and PIK3CA, in tailoring neoadjuvant regimens. Furthermore, the review emphasizes the need for a multidisciplinary approach to navigate the complexities of CRLM. Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies. The management of progression following neoadjuvant chemotherapy requires a tailored approach, acknowledging the diverse biological behaviors that may emerge. In conclusion, this review aims to provide a comprehensive perspective on the considerations, challenges, and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM. By combining evidence-based insights with practical experiences, we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.

Perioperative Chemotherapy Including Bevacizumab in Potentially Curable Metastatic Colorectal Cancer: Long-Term Follow-Up of the ASSO-LM1 Trial.

In 2007, the ASSO-LM1 trial, a multicenter prospective study, was initiated to investigate the resectability (R0) rate following preoperative combination therapy with XELOX and bevacizumab in patients with potentially resectable colorectal liver metastases. Six cycles of systemic therapy were administered preoperatively, although the sixth cycle did not include bevacizumab, resulting in 5 weeks between the last bevacizumab dose and surgery. Treatment with bevacizumab plus XELOX was restarted for another six cycles postoperatively. In total, 43 patients were enrolled in the ASSO-LM1 trial. Eight patients were ineligible for resection due to protocol violation and progression in two patients. The resectability of operated patients was 97% with 34 R0 resections and one R1 resection. Postoperative morbidity occurred in 22% of patients, of which three operative revisions were related to the primary tumor resection. Efficacy results for response in 38 eligible patients confirmed an ORR of 66%, 31% SD and 3% PD according to RECIST. Preoperative grade 3/4 adverse events were 17% diarrhea, 5% HFS and 5% thromboembolic events. Overall survival significantly differed depending upon the fulfillment of adjuvant treatment in curative resected patients (59.1 mo vs. 30.8 mo). In conclusion, the ASSO-LM1 trial is a hypothesis-generating study confirming the prognostic benefits of perioperative therapy with XELOX and bevacizumab in patients with metastatic colorectal cancer confined to the liver.

Impact of Primary Tumor Location on Demographics, Resectability, Outcomes, and Quality of Life in Finnish Metastatic Colorectal Cancer Patients (Subgroup Analysis of the RAXO Study).

The primary tumor location (PTL) is associated with the phenotype, metastatic sites, mutations, and outcomes of metastatic colorectal cancer (mCRC) patients, but this has mostly been studied according to sidedness (right vs. left sided). We studied right colon vs. left colon vs. rectal PTL in a real-life study population (n = 1080). Health-related quality of life (HRQoL) was assessed multi-cross-sectionally with QLQ-C30, QLQ-CR29, EQ-5D, and 15D. A chi-square, Kaplan-Meier, and Cox regression were used to compare the groups. The PTL was in the right colon in 310 patients (29%), the left colon in 396 patients (37%), and the rectum in 375 patients (35%). The PTL was associated with distinct differences in metastatic sites during the disease trajectory. The resectability, conversion, and resection rates were lowest in the right colon, followed by the rectum, and were highest in the left colon. Overall survival was shortest for right colon compared with left colon or rectal PTL (median 21 vs. 35 vs. 36 months), with the same trends after metastasectomy or systemic therapy only. PTL also remained statistically significant in a multivariable model. The distribution of symptoms varied according to PTL, especially between the right colon (with general symptoms of metastases) and rectal PTL (with sexual- and bowel-related symptoms). mCRC, according to PTL, behaves differently regarding metastatic sites, resectability of the metastases, outcomes of treatment, and HRQoL.

Preoperative predictors for non-resectability in perihilar cholangiocarcinoma.

INTRODUCTION: Explorative laparotomy without subsequent curative-intent liver resection remains a major clinical problem in the treatment of perihilar cholangiocarcinoma (pCCA). Thus, we aimed to identify preoperative risk factors for non-resectability of pCCA patients. MATERIAL AND METHODS: Patients undergoing surgical exploration between 2010 and 2022 were eligible for the analysis. Separate binary logistic regressions analyses were used to determine risk factors for non-resectability after explorative laparotomy due to technical (tumor extent, vessel infiltration) and oncological (peritoneal carcinomatosis, distant nodal or liver metastases)/liver function reasons. RESULTS: This monocentric cohort comprised 318 patients with 209 (65.7%) being surgically resected and 109 (34.3%) being surgically explored [explorative laparotomy: 87 (27.4%), laparoscopic exploration: 22 (6.9%)]. The median age in the cohort was 69 years (range 60-75) and a majority had significant comorbidities with ASA-Score ≥ 3 (202/318, 63.5%). Statistically significant (p < 0.05) risk factors for non-resectability were age above 70 years (HR = 3.76, p = 0.003), portal vein embolization (PVE, HR = 5.73, p = 0.007), and arterial infiltration > 180° (HR = 8.05 p < 0.001) for technical non-resectability and PVE (HR = 4.67, p = 0.018), arterial infiltration > 180° (HR = 3.24, p = 0.015), and elevated CA 19-9 (HR = 3.2, p = 0.009) for oncological/liver-functional non-resectability. CONCLUSION: Advanced age, PVE, arterial infiltration, and elevated CA19-9 are major risk factors for non-resectability in pCCA. Preoperative assessment of those factors is crucial for better therapeutical pathways. Diagnostic laparoscopy, especially in high-risk situations, should be used to reduce the amount of explorative laparotomies without subsequent liver resection.

Surgical and Interventional Management of Liver Metastasis.

Colorectal cancer is one of the most common cancers diagnosed worldwide. While the incidence of colorectal cancer has been declining since the adoption of screening colonoscopy, the findings of liver metastasis are still found in up to 25% of patients at diagnosis. The management of liver metastasis has evolved over the past two to three decades, and survival rates have improved secondary to improved systemic therapy, surgical options, and local therapies. In this article, we aim to review the available surgical and ablative options for management of colorectal liver metastasis, as well as appropriate imaging and patient selection.