Resection Of Primary Tumor Research Articles

Evaluating the Quality of Primary Transurethral Resection of Bladder Tumor: A Nine-Year Review at a Tertiary Healthcare Center.

This study aimed to assess the quality of primary transurethral resection of bladder tumor (TURBT) procedures performed at Aga Khan University Hospital (AKUH) over nine years, focusing on proper documentation, completeness of tumor resection, quality of histopathology reports, complication rates, and adherence to European Association of Urology (EAU) guidelines. A retrospective analysis of patients aged 25-75 who underwent primary TURBT at AKUH between 2010 and 2019 was done. Patients with incomplete records, concomitant procedures, or those who underwent emergency TURBT were excluded. Data was collected on patient demographics, clinical presentation, intraoperative details, and histopathology reports. Statistical analysis was performed using SPSS Version 27.0. 300 patients were initially identified, with 265 meeting the inclusion criteria. The mean age was 61.5 years, with 83% being male. Complete tumor resection was achieved in 35% (n=92) of cases, while deep biopsy was taken in 85% (n=226). Detrusor muscle (DM), a marker of resection quality, was noted in 75% (n=200) of histopathology reports. However, documentation quality varied, with 54% (n=143) of cases lacking clear information on resection completeness. The administration of a single instillation of a chemotherapeutic agent (SICA) was recorded in 79% (n=210) of patients, and the 30-day postoperative complication rate was monitored. The study highlights areas for improvement in the quality of TURBT procedures at AKUH, particularly in the documentation of resection completeness and adherence to established guidelines. Ensuring thorough resection and proper documentation is critical to optimizing patient outcomes and future management plans.

Shoulder Reconstruction Using a 3D Printed ‘Gigaprosthesis’ Following Resection of Massive Primary Bone Tumour

Shoulder Reconstruction Using a 3D Printed ‘Gigaprosthesis’ Following Resection of Massive Primary Bone Tumour

Improved survival after primary tumor resection in distant metastasis medullary thyroid carcinoma: a population-based cohort study with propensity score matching

Few studies have investigated the impact of primary tumor resection (PTR) on patients with distant metastasis medullary thyroid carcinoma (DMMTC). This population-based study aims to assess the application of PTR in DMMTC patients, ascertain its benefits, and identify optimal surgical indications. DMMTC Patients diagnosed between 2010 and 2020 were included through the Surveillance, Epidemiology, and End Results (SEER) program. Logistic regression analysis identified driving factors of surgical decision-making. Propensity score matching (PSM), Kaplan–Meier method, and Cox regression were utilized to compare overall survival (OS) and disease-specific survival (DSS) between surgical and non-surgical groups. Subgroup analyses were performed to determine optimal surgical indications. Of 238 DMMTC patients included, 122 (51.3%) patients underwent PTR. Extrathyroidal extension and N1 stage emerged as independent factors promoting the surgical decision. PSM-adjusted survival analyses revealed significant advantages in both OS and DSS for the surgical group. Moreover, subgroup analyses indicated that except for patients aged ≥ 65 years, tumors ≤ 20 mm, or with multiple metastasized sites (> 1), the others significantly benefit from PTR. PTR significantly improves prognosis in selected DMMTC patients. The decision to undergo PTR in other patients should be based on a comprehensive assessment of the disease, surgeon’s experience, and family discussions for potential survival benefits.

Efficacy of anti-epidermal growth factor antibody rechallenge in RAS/BRAF wild-type metastatic colorectal cancer: a multi-institutional observational study

PurposeTo investigate circulating tumor DNA (ctDNA) RAS mutant (MT) incidence before salvage-line treatment and the clinicopathological features and molecular biological factors associated with the efficacy of anti-epithelial growth factor receptor (EGFR) monoclonal antibody (mAb) rechallenge for tissue RAS/BRAF wild type (WT) metastatic colorectal cancer (mCRC).MethodsThis multi-institutional retrospective observational study included 74 patients with mCRC with tissue RAS/BRAF WT refractory to first-line chemotherapy containing anti-EGFR mAb. ctDNA RAS status was assessed using the OncoBEAM™ RAS CRC Kit. We explored the clinicopathological features associated with ctDNA RAS status and the factors related to anti-EGFR mAb rechallenge efficacy in multivariate Cox proportional hazard regression.ResultsThe incidence of RAS MT in ctDNA was 40.5% (30/74), which was associated with primary tumor resection (P = 0.016), liver metastasis (P < 0.001), and high tumor marker levels (P < 0.001). Among the 39 patients treated with anti-EGFR mAb rechallenge, those with ctDNA RAS WT showed significantly longer progression-free survival (PFS) than those with ctDNA RAS MT (median 4.1 vs. 2.7 months, hazard ratio [HR] = 0.39, P = 0.045). Patients who responded to first-line anti-EGFR mAb showed significantly longer PFS (HR = 0.21, P = 0.0026) and overall survival (OS) (HR = 0.23, P = 0.026) than those with stable disease.ConclusionsThe incidence of ctDNA RAS MT mCRC was 40.5%, which was associated with liver metastases and high tumor volumes. Anti-EGFR mAb rechallenge may be effective for patients with mCRC who responded to first-line chemotherapy containing anti-EGFR mAb. No patients with RAS MT in ctDNA responded to anti-EGFR mAb rechallenge.

No survival benefit of primary tumor resection for non-small cell lung cancer patients with unexpectedly detected pleural disseminated nodules in the era of targeted therapy.

Non-small cell lung cancer (NSCLC) patients with pleural dissemination are generally contraindicated for surgery. This study aimed to investigate the survival benefits of primary tumor resection for NSCLC patients with unexpectedly detected pleural disseminated nodules during thoracotomy in the era of targeted therapy. Of the 4984 patients with NSCLC who underwent surgery without induction therapy between 2000 and 2021, we retrospectively evaluated 90 (1.8%) patients with unexpectedly detected pleural disseminated nodule. Survival analyses were performed with Kaplan-Meier methods and Cox proportional hazards regression. Among the evaluated patients, 58 were male, the median age was 67, and 77 (86%) were diagnosed with adenocarcinoma. Exploratory thoracotomy was performed in 21 (23%), and primary tumor resection was performed in 69 (77%) patients, including pneumonectomy in four, lobectomy in 39, and sublobar resection in 26. Epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase rearrangement were detected in 33 (37%) and 4 (4%) cases, respectively. Among them, 31 patients received targeted therapy. The overall survival (OS) was not significantly different between patients with primary tumor resection and exploratory thoracotomy (5-year OS rate: 30.2% vs. 27.8%, p = 0.81). Multivariable analysis revealed that sex (p = 0.02) and targeted therapy (p < 0.01) were independent prognostic factors for OS. Survival outcomes in patients who received targeted therapy were significantly better regardless of primary tumor resection. Primary tumor resection might not affect the survival in NSCLC patients with unexpectedly detected pleural disseminated nodules in the era of targeted therapy.

Predictive risk factors for resection surface-related complications after laparoscopic simultaneous resection of primary colorectal tumor and synchronous liver metastases: a single-center retrospective study.

Laparoscopic simultaneous resection (LSR) of primary colorectal tumors and synchronous colorectal liver metastases (sCRLM) has been recently performed. This study aimed to evaluate the postoperative outcomes after LSR and determine the risk factors for resection surface-related complications (RSRC), such as postoperative biliary fistula and liver-transection surface abscess. Between 2009 and 2022, consecutive patients with sCRLM who underwent LSR were included. We retrospectively analyzed clinicopathological data, including intraoperative factors and postoperative outcomes. The difficulty level of all liver resections was classified according to the IWATE difficulty scoring system (DSS). We then performed univariate and multivariate analyses to identify the risk factors for RSRC. Of the 112 patients, 94 (83.9%) underwent partial hepatectomy and colorectal surgery. The median DSS score was 5 points (1-11), with 12 (10.7%) patients scoring ≥ 7 points. Postoperative complications were observed in 41 (36.6%) patients, of whom 16 (14.3%) experienced severe complications classified as Clavien-Dindo grade IIIa or higher. There was no postoperative mortality. The most common complication was RSRC (19 patients, 17.0%). Multivariate analysis identified American Society of Anesthesiologists (ASA) classification ≥ 3 [odds ratio (OR) 10.3, 95% confidence interval (CI) 1.37-77.8; P = 0.023], DSS score ≥ 7 points (OR 5.08, 95% CI 1.17-20.0; P = 0.030), and right-sided colectomy (OR 4.67, 95% CI 1.46-15.0; P = 0.009) as independent risk factors for RSRC. Postoperative hospital stays were significantly longer for patients with RSRC than for those without RSRC (22 days vs. 11days; P < 0.001). Short-term outcomes of LSR for patients with sCRLM were acceptable in an experienced center. RSRC was the most common complication, and high-difficulty hepatectomy, right-sided colectomy, and ASA classification ≥ 3 were independent risk factors for RSRC.

Cancer histology in metastatic lymph node predicts prognosis in patients with node-positive stage IV colorectal cancer.

Appropriate prognostic indicators are required for patients with stage IV colorectal cancer (CRC). Lymph node metastasis mainly involves four histological types of CRC. Some metastatic lymph nodes (mLNs) showing cribriform carcinoma are associated with distant metastasis in patients with node-positive CRC and are correlated with recurrence and survival in stage III disease. However, the significance of mLN histology in the prognosis of patients with node-positive stage IV disease remains unclear. We enrolled 449 consecutive patients with CRC who underwent primary tumor resection with lymph node dissection between January 2011 and November 2018. This study included 88 patients with node-positive stage IV CRC and synchronous or metachronous distant metastases. We retrospectively investigated the association between cancer histology in the mLNs based on our classification and cancer-specific survival (CSS) in patients with node-positive stage IV CRC. Kaplan-Meier analysis showed that CSS was better in patients with CRC and all the mLNs showing tubular-type carcinoma. In contrast, patients with at least some mLNs showing poorly differentiated-type carcinoma had poor prognosis. Multivariate analysis showed that "all mLNs showing tubular-type carcinoma" was an independent good prognostic factor for CSS in patients with node-positive stage IV CRC. In addition, "at least some mLNs showing poorly differentiated-type carcinoma" was an independent poor prognostic factor for CSS in patients with node-positive stage IV disease. The histological type of the mLN may indicate a better or poor prognosis for patients with stage IV CRC.

Biphasic co-detection of melanoma aneuploid tumor cells and tumor endothelial cells in guidance of specifying the field cancerized surgical excision margin and administering immunotherapy

An optimum safety excision margin (EM) delineated by precise demarcation of field cancerization along with reliable biomarkers that enable predicting and timely evaluating patients’ response to immunotherapy significantly impact effective management of melanoma. In this study, optimized biphasic “immunofluorescence staining integrated with fluorescence insitu hybridization” (iFISH) was conducted along the diagnosis-metastasis-treatment-cellular MRD axis to longitudinally co-detect a full spectrum of intact CD31− aneuploid tumor cells (TCs), CD31+ aneuploid tumor endothelial cells (TECs), viable and necrotic circulating TCs (CTCs) and circulating TECs (CTECs) expressing PD-L1, Ki67, p16 and Vimentin in unsliced specimens of the resected primary tumor, EM, dissected sentinel lymph nodes (SLNs) and peripheral blood in an early-stage melanoma patient. Numerous PD-L1+ aneuploid TCs and TECs were detected at the conventional safety EM (2 cm), quantitatively indicating the existence of a field cancerized EM for the first time. Contrary to highly heterogeneous PD-L1 expression and degrees of Chr8 aneuploidy in TCs and TECs in the primary lesions as well as CTCs and CTECs in peripheral blood, almost all TCs and TECs in SLNs and EM were homogeneously PD-L1+ haploid cells. Dynamic monitoring and cellular MRD assessment revealed that, in contrast to PD-L1+ CTCs being responsive to the immune checkpoint inhibitor (ICI-anti-PD-1), multiploid (≥pentasomy 8) PD-L1+ and Ki67+ CTECs were respectively resistant to ICI-sensitized T cells. In therapeutically stressed lymphatic and hematogenous metastatic cascades, stratified phenotypic and karyotypic profiling of iFISH tissue and liquid biopsied TCs, TECs, CTCs and CTECs in future large-cohort studies will enable appropriate re-specification of the optimal safety EM and distribution mapping of in-depth characterized, subcategorized target cells to help illustrate their metastatic relevance, ultimately improving risk stratification and clinical intervention of tumor progression, metastases, therapy resistance and cancer relapse.

Principles of Defect Reconstruction After Wide Resection of Primary Malignant Bone Tumors of the Calcaneus: A Contemporary Review.

Visual AbstractThis is a visual representation of the abstract.

Development and internal validation of individualized prediction models of overall survival and 6-month mortality among patients with synchronous early-onset colorectal liver metastases

BackgroundEarly-onset colorectal cancer with synchronous liver metastasis (EO-CRLM) is a growing concern with a grim prognosis. MethodsEO-CRLM patients were identified from the National Cancer Database. Random survival forest model and random forest (RF) model were developed for the prediction of overall survival (OS) and 6-month mortality, respectively. ResultsThe variables with top contributions for random survival forest model of OS included primary tumor resection, chemotherapy and bone metastases. The AUCs of 1-, 3- and 5-year OS were 0.787, 0.763 and 0.761, respectively. The individualized risk profile predicted by the models closely aligned with the actual survival outcomes observed for the patients. The variables with top contributions for RF model for 6-month mortality included chemotherapy, Charlson-Deyo comorbidity score and presence of tumor deposits. RF model for 6-month mortality resulted in an AUC of 0.821 in training set, 0.828 in cross-validation and 0.852 in testing cohort. RF models for OS and 6-month mortality exhibited great net benefit with favorable clinical utility. ConclusionThe models generated in this study accurately identified EO-CRLM patients at risk of worse OS and short-term mortality, which may complement standard clinical assessment and aid in creation of advanced care planning.

Patients with stage IV colorectal carcinoma selected for palliative primary tumor resection and systemic therapy survive longer compared with systemic therapy alone - A retrospective comparative cohort study.

To compare the survival of palliative stage IV colorectal cancer patients selected for primary tumor resection and systemic treatment (PTR+SYST) to patients with systemic treatment only (SYST). About 20-25% of all colorectal cancer patients are diagnosed with stage IV disease. The benefit of primary tumor resection in the palliative situation is therefore of high concern. However, empirical evidence from randomized and observational studies is inconsistent. Mortality after PTR and systemic treatment was compared to systemic treatment alone in a retrospective observational cohort of patients diagnosed 2012-2020 from the cancer registry in the federal state of Brandenburg (Germany), excluding patients with rectal cancer of the lower two-thirds, emergency procedures, unknown ECOG status, ECOG >2, unknown metastatic status or unclear grading. Of 480 patients, 416 died during an average follow-up of 23 months in mean. 12-months survival was 75% after PTR+SYST compared with 49% after SYST (HR=0.39, 95% CI 0.29-0.53, P<0.001). The difference persisted to 36 months (28% vs. 13%, HR=0.53, 95% CI 0.43-0.66, P<0.001). Results were similar after multivariate adjustment, propensity score matching and delayed entry. Patients with stage IV colorectal carcinoma who are selected for primary tumor resection in combination with systemic therapy and who receive such treatment survive longer compared with patients who receive only systemic treatment. Whether the difference is due to selection of patients or PTR remains unclear. At present, current practice of selecting patients for PTR appears to do no harm.

Three-dimensional reconstruction technology in the preoperative workup of complex hepatic resections. Our experience on 11 consecutive cases.

Three-dimensional liver modeling can be a useful tool when planning the preoperative strategy in liver surgery. The present study aims to review our case series of patients requiring complex hepatic resections for primary and secondary liver tumors, and for whom 3D models were built, to add further evidence in this direction. All consecutive patients undergoing complex liver resection were enrolled. Cross-sectional triphasic CT images were obtained for each patient. DICOM images were processed, and full virtual 3D models were generated. The additional details provided by 3D models were employed to better understand the anatomy, to define the most adequate surgical pathway, and, in case, to switch to a different surgical procedure. From January 2020 to September 2022, 11 complex hepatic resections requiring 3D reconstruction technology were performed. Eight 3D models scored ≥ 15 points in the quality control system. A detailed analysis of each case was reported. In three cases (27%) 3DVT helped to understand the anatomy and/or to detect vascular abnormalities. In six cases (54.5%) 3DVT led to a variation of the surgical planning. 3DVT may be helpful in planning preoperatively the most appropriate surgical procedure. Further large-scale, well-designed studies are needed to prove its true effectiveness in HPB surgical oncology.

Larger Tumor Size and Elevated Serum Chromogranin A Levels Predict Metastatic Disease on DOTATATE Imaging in Patients with Gastroenteropancreatic Neuroendocrine Tumors.

DOTATATE PET/CT (DOTATATE) is superior to conventional imaging in detecting metastasis for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, limited availability, high-cost, and additive radiation exposure necessitate guidelines for its use. This study seeks to investigate the relationship between clinical characteristics and metastasis on DOTATATE. This was a retrospective analysis of 815 patients who underwent DOTATATE at UCLA from 2014 to 2022. After applying inclusion and exclusion criteria, the study cohort consisted of 163 patients with pathologically diagnosed GEP-NETs, who either underwent primary tumor resection within 1-year prior, or had not undergone resection at the time of DOTATATE imaging. The presence of metastasis was determined using DOTATATE. Fisher's exact test, chi-squared test, and Mann-Whitney test were conducted to compare intergroup difference. Multivariate analysis was performed to identify clinical characteristics associated with metastasis on DOTATATE. Of patients with GEP-NETs, 40.5% (n = 66) were diagnosed with metastases by using DOTATATE. Those with metastatic disease were more likely to exhibit a larger primary tumor size (median 3.4 vs. 1.2, cm, P<0.001), elevated serum chromogranin A level (CgA, median 208 vs. 97, mg/ml, P = 0.005), and higher tumor grade (P < 0.001). Primary tumor size ≥2 cm and serum CgA level ≥150 ng/mL for metastatic disease had a sensitivity and specificity of 64% and 89%, and 72% and 59%, respectively. Multivariate analysis demonstrated that primary tumor size (≥2/<2, cm, odds ratio [OR] 47.90, P < 0.001), tumor functionality (functional/nonfunctional, adjusted OR 10.17 P = 0.008), serum CgA level (≥150/<150, ng/ml, OR 6.25, P = 0.005), and tumor grade G2 (G2/G1, OR 9.6, P < 0.001) were independently associated with metastases on DOTATATE. Among patients with GEP-NETs, primary tumor size ≥2 cm, serum CgA level ≥150 ng/mL, and tumor grade G2 are associated with an increased risk of metastases on DOTATATE, and these predictors may be helpful to identify patients where DOTATATE is indicated for complete staging.

Spatial proteomic landscape of primary and relapsed hepatocellular carcinoma reveals immune escape characteristics in early relapse.

Surgical resection serves as the principal curative strategy for hepatocellular carcinoma (HCC), yet the incidence of postoperative recurrence remains alarmingly high. However, the spatial molecular structural alterations contributing to postoperative recurrence in HCC are still poorly understood. We employed imaging mass cytometry to profile the in-situ expression of 33 proteins within 358,729 single cells of 92 clinically annotated surgical specimens from 46 patients who were treated with surgical resections for primary and relapsed tumors. We revealed the recurrence progression of HCC was governed by the dynamic spatial distribution and functional interplay of diverse cell types across adjacent normal, tumor margin, and intratumor regions. Our exhaustive analyses revealed an aggressive, immunosuppression-related spatial ecosystem in relapsed HCC. Additionally, we illustrated the prominent implications of the TME of tumor margins in association with relapse HCC. Moreover, we identified a novel subpopulation of dendritic cells (PDL1+CD103+ DCs) enriched in the peritumoral area that correlated with early postoperative recurrence, which was further validated in an external cohort. Through the analysis of scRNA-seq data, we found the interaction of PDL1+CD103+ DCs with regulatory T cells and exhausted T cells enhanced immunosuppression and immune escape via multiple ligand-receptor pathways. We comprehensively depicted the spatial landscape of single-cell dynamics and multicellular architecture within primary and relapsed HCC. Our findings highlight spatial organization is a prominent determinant of HCC recurrence and provide a valuable insight into the immune evasion mechanisms driving recurrence.

Influence of the COVID-19 Pandemic on Patients with Rectal Cancer.

Objectives: The COVID-19 pandemic and its associated restrictions have resulted in delayed diagnoses across various tumor entities, including rectal cancer. Our hypothesis was based on the expectation of a reduced number of primary operations due to higher tumor stages compared to the control group. Methods: In a single-center retrospective study conducted from 1 March 2018 to 1 March 2022, we analyzed 120 patients with an initial diagnosis of rectal cancer. Among them, 65 patients were part of the control group (pre-COVID-19), while 55 patients were included in the study group (during the COVID-19 pandemic). We compared tumor stages, treatment methods, and complications, presenting data as absolute numbers or mean values. Results: Fewer primary tumor resections during the COVID-19 pandemic (p = 0.010), as well as a significantly lower overall number of tumor resections (p = 0.025) were seen compared to the control group. Twenty percent of patients in the COVID-19 group received their diagnosis during lockdown periods. These patients presented significantly higher tumor stages (T4b: 27.3% vs. 6.2%, p = 0.025) compared to the control group prior to the pandemic. In addition, more patients with angiolymphatic invasion (ALI) were identified in the COVID-19 group following neoadjuvant treatment compared to the control group (p = 0.027). No differences were noted between the groups regarding complications, stoma placement, or conversion rates. Conclusions: The COVID-19 pandemic, particularly during lockdown, appears to have contributed to delayed diagnoses, resulting in higher tumor stages and a decreased number of surgeries. The quality of rectal cancer treatment can be maintained under pandemic conditions.

Use of 3D-CT-derived psoas major muscle volume in defining sarcopenia in colorectal cancer

BackgroundSarcopenia is characterized by reduced skeletal muscle volume and is a condition that is prevalent among elderly patients and associated with poor prognosis as a comorbidity in malignancies. Given the aging population over 80 years old in Japan, an understanding of malignancies, including colorectal cancer (CRC), complicated by sarcopenia is increasingly important. Therefore, the focus of this study is on a novel and practical diagnostic approach of assessment of psoas major muscle volume (PV) using 3-dimensional computed tomography (3D-CT) in diagnosis of sarcopenia in patients with CRC.MethodsThe subjects were 150 patients aged ≥ 80 years with CRC who underwent primary tumor resection at Juntendo University Hospital between 2004 and 2017. 3D-CT measurement of PV and conventional CT measurement of the psoas major muscle cross-sectional area (PA) were used to identify sarcopenia (group S) and non-sarcopenia (group nS) cases. Clinicopathological characteristics, operative results, postoperative complications, and prognosis were compared between these groups.ResultsThe S:nS ratios were 15:135 for the PV method and 52:98 for the PA method. There was a strong positive correlation (r = 0.66, p < 0.01) between PVI (psoas major muscle volume index) and PAI (psoas major muscle cross-sectional area index), which were calculated by dividing PV or PA by the square of height. Surgical results and postoperative complications did not differ significantly in the S and nS groups defined using each method. Overall survival was worse in group S compared to group nS identified by PV (p < 0.01), but not significantly different in groups S and nS identified by PA (p = 0.77). A Cox proportional hazards model for OS identified group S by PV as an independent predictor of a poor prognosis (p < 0.05), whereas group S by PA was not a predictor of prognosis (p = 0.60).ConclusionsThe PV method for identifying sarcopenia in elderly patients with CRC is more practical and sensitive for prediction of a poor prognosis compared to the conventional method.

Chemotherapy and liver transplantation versus chemotherapy alone in patients with definitively unresectable colorectal liver metastases: A prospective multicentric randomized trial (TRANSMET).

3500 Background: Despite the increasing efficacy of chemotherapy (CT) and advances in surgical techniques for initially unresectable colorectal liver metastases (uCLM), secondary resection rate remains low. For definitively uCLM, CT remains the standard of care but liver transplantation (LT) has shown promising results. This first randomized trial aimed to assess the efficacy of CT combined to LT for uCLM. Methods: Patients with definitively uCLM from resected BRAF non mutated colorectal cancer, having responded to CT (≥ 3 months and ≤ 3 lines) in the absence of extrahepatic disease, were validated by an independent experts’ committee and randomly assigned (1:1) to receive CT and LT (CT+LT arm) or CT alone (CT arm). The primary endpoint was 5-year overall survival (OS). Secondary endpoints were progression free survival (PFS) and patterns of recurrence. In order to detect a 40% difference in OS from 10% (CT) to 50% (CT+LT) (2-sided α level 5% - 90% power), 29 events were initially needed, secondly re-estimated to 50 according to the rate of patients not receiving LT in the CT+LT arm during the study. Results: Between February 2016 and July 2021, 94 patients (median age 54 years, IQR 47-59) were randomly assigned to CT+LT arm (n = 47) or CT arm (n = 47). Median number and maximal diameter of uCLM at diagnosis were 20 (13-25) and 51.5 (37-78) mm, respectively. At randomization, objective response was obtained after a median number of 20 (14-27) CT cycles during 1 (44%), 2 (40%) or 3 (16%) lines. Median delay between primary tumour resection and randomisation was 14.6 (10.6-22.3) months. In CT+LT arm, 38 (81%) underwent LT after a median of 51 (30-65) days from randomization. Nine patients did not receive LT because of tumour progression during the waiting time or intraoperative finding of extrahepatic disease. Three (8%) of the 38 transplanted patients were retransplanted, one of whom (3%) died postoperatively. Post-transplant CT was administered in 26 (68%) patients. In CT arm, 9 (19%) patients unexpectedly underwent partial hepatectomy (7) or LT (2). In intent-to-treat analysis, 5-year OS was 57% in CT+LT arm and 13% in CT alone arm (log-rank test: p = 0.0003 - HR 0.37; 95%CI 0.21-0.65). In per protocol analysis, 5-year OS rate was 73% and 9%, respectively (HR 0.16; 95%CI 0.07-0.33). Median PFS was 17.4 months versus 6.4 months (HR 0.34; 95%CI 0.20-0.58), respectively. Among transplanted patients, 28 (74%) had lung (39%), liver (3%), other (21%) or multisite (11%) recurrence, optionally treated by surgery (36%) or local ablation (11%). Fifteen (40%) patients were ultimately disease-free. Conclusions: LT combined with CT significantly improved survival in selected patients with uCLM compared to CT alone. These results argue for validating LT as a new standard option that may change the treatment strategy for liver-only uCLM patients. Clinical trial information: NCT02597348 .

Association of lung cancer-associated cachexia with the metastatic spread to pleura.

12095 Background: Cancer-associated cachexia (CAC), a major contributor to mortality in patients with non-small cell lung cancer (NSCLC), is characterized by alterations in body composition. Here, we explore the associations between body composition changes and the pattern of lung cancer metastatic spread. Methods: Computer tomography (CT) images from cancer diagnosis and recurrence were used to quantify subcutaneous and visceral adipose tissue (SAT, VAT) and skeletal muscle (SKM) tissue areas at the 3rd lumbar vertebrae level, using an DAFS AI-based software, Voronoi Analytics, in 101 NSCLC pts, who relapsed after surgical treatment of the primary tumor at the Medical University of Gdansk Hospital. The decrease in SKM, SAT and VAT of more than 5% or 10% at cancer relapse was compared with the pattern of cancer recurrence. Results: The median time to recurrence after primary tumor resection was 1.6 years (0.4–6.4 years). There were 38% local or regional recurrences, 59% distant recurrences, and 13% second primary lung cancers. Among the cases with distant recurrence, there were 19% brain recurrences, 22% pleural metastases, 34% lung metastases, 17% bone metastases, and 11% cases of liver relapse. More than one site of distant recurrence occurred in 51 (50%) of patients. Loss of &gt; 5% of SKM, SAT and VAT occurred in 61%, 33% and 41% respectively. Loss of &gt;5% or &gt;10% of SKM was associated with the pleural metastases at the time of cancer recurrence, ( P &lt; 0.001). Median muscle loss was –11.6% for patients with pleural relapse and –5.3 % for patients with other metastatic locations ( P &lt; 0.001). There were no significant associations between other body composition changes and the pattern of recurrences, tumor histology or age. Conclusions: NSCLC relapse to the pleura after surgical treatment of the primary tumor, appears to be associated with a decrease in the skeletal muscle compartment. This finding may inform the design of the future studies aiming to investigate molecular correlates of sarcopenia and cancer-associated cachexia.

Use of circulating tumor DNA (ctDNA) to affect the adjuvant or post-adjuvant treatment of patients with stage III and high-risk stage II resected colon cancer: The ERASE-CRC project by GONO.

TPS3644 Background: Three or 6 months of fluoropyrimidines plus oxaliplatin is the standard adjuvant therapy for stage III and high-risk stage II colon cancer, but 20-25% of patients relapse. CtDNA is a promising biomarker of minimal residual disease (MRD) after primary tumor resection and a potential guide in the adjuvant treatment decision-making process. Indeed, ctDNA-positivity after surgery or at the end of adjuvant therapy is associated with higher risk of recurrence. Intensifying the adjuvant and/or the post-adjuvant treatment could be a valuable strategy in these cases. CtDNA clearance has been suggested as a predictor of long-term clinical outcome. Methods: ERASE-CRC is a prospective, open-label, multicentre study, including three phase 2 trials enrolling ctDNA-positive patients with radically resected stage III or high-risk stage II (one major prognostic factor or at least two minor prognostic factors) adenocarcinoma of the colon or intraperitoneal rectum. CtDNA is centrally assessed through a tissue-informed method, F1Tracker. In the phase II ERASE-CRC Part 1 study, patients that are ctDNA-positive after surgery (2-6 weeks) are randomized 1:1 to 6 months of either FOLFOX or CAPOX at investigators’ choice (standard arm) versus FOLFOXIRI (experimental arm). In the phase II single arm ERASE-HER2 study, ctDNA-positive patients with HER2 amplified and RAS wild-type tumors received FOLFOX plus trastuzumab and tucatinib for 12 cycles. In the phase II ERASE-CRC Part 2 study, ctDNA-positive patients after the end of an oxaliplatin-based adjuvant therapy (either in the context or outside ERASE-CRC Part 1 or ERASE-HER2) are randomized 1:2 to observation (standard arm) or trifluridine/tipiracil for 6 cycles (experimental arm). The primary endpoint is the clearance rate of ctDNA after the adjuvant (ERASE-CRC Part 1 and ERASE-HER2) or the post-adjuvant treatment (ERASE-CRC Part 2). 300 patients will be randomized in ERASE-CRC Part 1 to detect a 15% difference in ctDNA clearance rate between the experimental and the standard arm with expected clearance rates of 65% and 50%, respectively, and 1-sided alpha and beta errors of 0.05 and 0.2, respectively. 18 patients will be enrolled in ERASE-HER2 to observe a ctDNA clearance rate of 80% with the targeted treatment ( versus 50% expected), and ctDNA clearance should be observed in 13 cases to consider the strategy promising. Finally, 159 patients will be randomized in ERASE-CRC Part 2 to detect a 15% difference in ctDNA clearance rate between the experimental and the standard arm with 20% and 5% expected clearance rates respectively, and 1-sided alpha and beta errors of 0.05 and 0.2, respectively. Approximately 40 Italian Oncology Units are participating in the study. Currently, 19 and 8 patients have been randomized in ERASE-CRC Part 1 or 2, respectively. NCT05062889. Clinical trial information: NCT05062889 .

Transoral robotic surgery in the diagnosis and treatment of primary unknown head and neck squamous cell carcinoma: A preliminary single centre experience.

Squamous cell carcinoma of unknown primary (CUP) in the head and neck is difficult to diagnose and treat. This report outlines 11 cases of CUP treated with transoral robotic surgery (TORS), aimed at investigating the diagnostic efficiency of primary tumour and radical resection effectiveness of TORS. 11 cases of CUP among 68 oropharyngeal cancer patients treated by TORS were analysed retrospectively. All the 11 cases received TORS with cervical lymph node dissection. Primary tumours were found in 8 cases (72.7%), 4 cases in the palatine tonsil and 4 cases in the base of the tongue. The average diameter of the primary tumour was 1.65cm. All patients resumed eating by mouth within 24h, no tracheotomy, no pharyngeal fistula and no postoperative death. The 3-year disease-free survival rate was 91%. TORS can improve the diagnostic efficiency of primary tumour of CUP and achieve good oncology and functional results.