Resection Therapy Research Articles

Survival analysis of laparoscopic surgery and open surgery for hilar cholangiocarcinoma: a retrospective cohort study

Background/purposeThis study compared the clinical efficacy and safety of laparoscopic versus open resection for hilar cholangiocarcinoma (HCCA) and analyzed potential prognostic factors.MethodsThe study included patients who underwent HCCA resection at our center from March 2012 to February 2022. Perioperative complications and postoperative prognosis were compared between the laparoscopic surgery (LS) and open surgery (OS) groups.ResultsAfter screening 313 HCCA patients, 68 patients were eligible for the study in the LS group (n = 40) and OS group (n = 28). Kaplan-Meier survival curve analysis revealed that overall survival > 2 years and 3-year disease-free survival (DFS) were more common in the LS than OS group, but the rate of 2-year DFS was lower in the LS group than OS group. Cox multivariate regression analysis revealed age (< 65 years), radical resection, and postoperative adjuvant therapy were associated with reduced risk of death (hazard ratio [HR] = 0.380, 95% confidence interval [CI] = 0.150–0.940, P = 0.036; HR = 0.080, 95% CI = 0.010–0.710, P = 0.024 and HR = 0.380, 95% CI = 0.150–0.960, P = 0.040), whereas preoperative biliary drainage was an independent factor associated with increased risk of death (HR = 2.810, 95% CI = 1.130–6.950, P = 0.026). Perineuronal invasion was identified as an independent risk factor affecting DFS (HR = 5.180, 95% CI = 1.170–22.960, P = 0.030).ConclusionsCompared with OS, laparoscopic HCCA resection does not significantly differ in terms of clinical efficacy. Age (<65 years), radical resection, and postoperative adjuvant therapy reduce the risk of death, and preoperative biliary drainage increases the risk of death.

Management of Intrahepatic Cholangiocarcinoma: A Narrative Review.

The management of resectable intrahepatic cholangiocarcinoma remains a challenge due to the high risk of recurrence. Numerous clinical trials have identified effective systemic therapies for advanced biliary tract cancer; however, fewer trials have evaluated systemic therapies in the perioperative period. The objective of this review is to summarize the current recommendations regarding the diagnosis, surgical resection, and systemic therapy for anatomically resectable intrahepatic cholangiocarcinoma. Our review demonstrates that surgical resection with microscopic negative margins and lymphadenectomy remains the cornerstone of treatment. High-level evidence regarding specific systemic therapies for use in resectable intrahepatic cholangiocarcinoma remains sparse, as most of the evidence is extrapolated from trials involving heterogeneous tumor populations. Targeted therapies are an evolving practice for intrahepatic cholangiocarcinoma with most evidence coming from phase II trials. Future research is required to evaluate the use of neoadjuvant therapy for patients with resectable and borderline resectable disease.

Novel Brain-Penetrant, Small-Molecule Tubulin Destabilizers for the Treatment of Glioblastoma.

Glioblastoma (GB) is the most lethal brain cancer in adults, with a 5-year survival rate of 5%. The standard of care for GB includes maximally safe surgical resection, radiation, and temozolomide (TMZ) therapy, but tumor recurrence is inevitable in most GB patients. Here, we describe the development of a blood-brain barrier (BBB)-penetrant tubulin destabilizer, RGN3067, for the treatment of GB. RGN3067 shows good oral bioavailability and achieves high concentrations in rodent brains after oral dosing (Cmax of 7807 ng/mL (20 μM), Tmax at 2 h). RGN3067 binds the colchicine binding site of tubulin and inhibits tubulin polymerization. The compound also suppresses the proliferation of the GB cell lines U87 and LN-18, with IC50s of 117 and 560 nM, respectively. In four patient-derived GB cell lines, the IC50 values for RGN3067 range from 148 to 616 nM. Finally, in a patient-derived xenograft (PDX) mouse model, RGN3067 reduces the rate of tumor growth compared to the control. Collectively, we show that RGN3067 is a BBB-penetrant small molecule that shows in vitro and in vivo efficacy and that its design addresses many of the physicochemical properties that prevent the use of microtubule destabilizers as treatments for GB and other brain cancers.

Abstract A074: Targeting dormant disseminated tumor cells and their permissive niche by pro-resolving mediators derived from resolution-phase macrophages

Abstract Metastatic breast cancer can recur years after primary tumor resection and adjuvant therapy and appears to arise from quiescent disseminated tumor cells (QDTC) that persist at distant sites and resist conventional therapies. To date there are no treatments to target QDTCs. Previously, the fibrotic-like microenvironment enriched with Type I collagen (Col-I) was shown to be required for the switch of QDTC to metastatic outgrowth in lungs of mice. Here, we examined whether soluble mediators secreted by ex-vivo generated pro-resolving CD11blow macrophages (CM-Mres) will reinstate resolution of inflammation thus inhibiting the establishment of the fibrotic-like-niche and in turn prevent the emergence of QDTC to metastatic outgrowth. Our findings indicate that CM-Mres promoted immune silencing of alveolar macrophages at the metastatic site where dormant DTCs reside. Immune silencing is one of the hallmarks of resolution of inflammation. Furthermore, CM-Mres inhibited the establishment of a fibrotic-like niche resulting in the inhibition of the metastatic outgrowth in vitro and in vivo. This was due to inhibition of fibroblasts differentiation to myofibroblasts independent of TGFbeta1 canonical signaling and abolishment of Col-I expression. Furthermore, CM-Mres deactivated myofibroblasts as part of the resolution process by inducing an increase in reactive oxygen species (ROS) via activation of NADPH oxidase. This in turn induced DNA damage leading to Go/G1 arrest and intrinsic apoptosis. Similarly, apoptosis mediated by oxidative stress was induced by CM-Mres in dormant and outbreaking QDTCs. Taken together our results demonstrate for the first time that by reinstating resolution of inflammation via physiological mediators, secreted by pro-resolving macrophages, can prevent metastatic outgrowth of QDTCs at their permissive site. Since conventional therapies fail to eradicate dormant DTCs and their transition to clinical metastasis, our findings hold great promise in the quest to identify novel strategies to prevent or treat recurrent metastatic disease. Citation Format: Odelya Gilon, Keren Weidenfeld, Hadell Samara, Yonatan Feuermann, Sagie Schif-Zuck, Sergei Butenko, Edmond Sabo, Amiram Ariel, Dalit Barkan. Targeting dormant disseminated tumor cells and their permissive niche by pro-resolving mediators derived from resolution-phase macrophages [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A074.

Comparison of outcomes following surgical resection, percutaneous ablation or stereotactic body radiation therapy in early-stage, solitary and small (≤3 cm) treatment-naïve hepatocellular carcinoma.

Stereotactic body radiation therapy (SBRT) is associated with high local control rates in hepatocellular carcinoma (HCC). This study reports the outcomes of SBRT compared to surgical resection (SR) and percutaneous ablation (PA) for treatment-naïve, solitary HCCs ≤3 cm. This was a retrospective study of patients with BCLC stage 0/A HCC with a single ≤3 cm lesion, treated with curative intent between 2016 and 2020. SBRT was used for patients considered unsuitable for SR or PA. The co-primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were treatment-related clinical toxicity rates and local control (LC) rates. There were 112 patients included in this study. SBRT was delivered in 36 patients (32.1%), 51 had PA (45.5%) and 25 underwent SR (22.3%). Median follow-up was 23 months (range, 3-60 months) from diagnosis. The 3-year PFS and OS were 67% and 69% following SBRT, 55% and 80% following PA, and 85% and 100% following SR, respectively. Patients in the SR cohort had significantly better 3-year PFS and OS compared to SBRT and PA groups (p = 0.03 and p = 0.04, respectively). There was no significant difference in PFS (p = 0.15) or OS (p = 0.23) between SBRT and PA treated patients. The 3-year LC rate for the entire cohort was 98%. In patients with treatment-naïve, early-stage solitary HCCs ≤3 cm, SBRT was associated with comparable PFS, OS and LC outcomes to PA. SBRT should be considered as a curative intent therapy to avoid treatment stage migration in this favourable prognostic cohort of patients.

Cholangiocarcinoma Insights: Established Foundations and Cutting-Edge Innovations from Dr. James Cleary’s Pioneering Research

This paper provides insights into the conventional understanding of biliary tract malignancies, with a specific focus on cholangiocarcinoma (CCA). We then delve into the groundbreaking ideas presented by Dr. James Cleary. CCA, originating from biliary tree cells, manifests diverse subtypes contingent upon anatomical localization and differentiation status. These variants exhibit discrete genetic aberrations, yielding disparate clinical phenotypes and therapeutic modalities. Intrahepatic, perihilar, and distal CCAs intricately involve distinct segments of the biliary tree, further categorized as well-differentiated, moderately differentiated, or poorly differentiated adenocarcinomas based on their histological differentiation. Understanding the etiological factors contributing to CCA development assumes paramount importance. Stratifying these factors into two groups, those unrelated to fluke infestations (e.g., viral hepatitis and fatty liver conditions) and those associated with fluke infestations (e.g., chronic liver inflammation), facilitates predictive modeling. The epidemiology of CCA exhibits global variability, with Southeast Asia notably displaying higher incidences attributed primarily to liver fluke infestations. Jaundice resulting from bile duct obstruction constitutes a prevalent clinical manifestation of CCA, alongside symptoms like malaise, weight loss, and abdominal pain. Diagnostic challenges arise due to the symptomatic overlap with other biliary disorders. Employing comprehensive liver function tests and imaging modalities such as computed tomography assumes a pivotal role in ensuring accurate diagnosis and staging. However, the definitive confirmation of CCA necessitates a biopsy. Treatment modalities, predominantly encompassing surgical resection and radiation therapy, hold curative potential, although a considerable subset of patients is deemed unresectable upon exploration. Challenges intensify, particularly in cases classified as cancer of unknown origin, underscoring the imperative for early intervention. Advancements in genomic sequencing have revolutionized precision medicine in CCA. Distinct genomic markers, including fibroblast growth factor receptor 2 (FGFR2) alterations and isocitrate dehydrogenase 1 (IDH1) mutations, have emerged as promising therapeutic targets. FGFR2 alterations, encompassing mutations and rearrangements, play pivotal roles in oncogenesis, with FGFR inhibitors demonstrating promise despite identified resistance mechanisms. Similarly, IDH1 inhibitors face challenges with resistance, despite encouraging early clinical trial results, prompting exploration of novel irreversible inhibitors. Dr. James Cleary’s illuminating discourse underscores the significance of diverse FGFR2 alterations and the potential of IDH1 inhibition in reshaping the treatment landscape for CCA. These findings unveil critical avenues for targeted therapeutic interventions, emphasizing the critical need for ongoing research to optimize outcomes in this challenging cancer subtype, incorporating innovative insights from Dr. Cleary.

Development and validation of a computed tomography-based radiomics signature to predict "highest-risk" from patients with high-risk gastrointestinal stromal tumor.

Some patients with high-risk gastrointestinal stromal tumor (GIST) experience disease progression after complete resection and adjuvant therapy. It is of great significance to distinguish these patients among those with high-risk GIST. Radiomics has been demonstrated as a promising tool to predict various tumors prognosis. From January 2006 to December 2018, a total of 100 high-risk GIST patients (training cohort: 60; validation cohort: 40) from Guangdong Provincial People's Hospital with preoperative enhanced computed tomography (CT) images were enrolled. The radiomics features were extracted and a risk score was built using least absolute shrinkage and selection operator-Cox model. The clinicopathological factors were analyzed and a nomogram was established with and without radiomics risk score. The concordance index (C-index), calibration plot, and decision curve analysis (DCA) were used to evaluate the performance of the radiomics nomograms. We selected 11 radiomics features associated with recurrence or metastasis. The risk score was calculated and significantly associated with disease-free survival (DFS) in both the training and validation group. Cox regression analysis showed that Ki67 was an independent risk factor for DFS [P=0.004, hazard ratio 4.615, 95% confidence interval (CI): 1.624-13.114]. The combined radiomics nomogram, which integrated the radiomics risk score and significant clinicopathological factors, showed good performance in predicting DFS, with a C-index of 0.832 (95% CI: 0.761-0.903), which was better than the clinical nomogram (C-index 0.769, 95% CI: 0.679-0.859) in training cohort. The calibration curves and the DCA plot suggested satisfying accuracy and clinical utility of the model. The CT-based radiomics nomogram, combined with the clinicopathological factors and risk score, has good potential to assess the recurrence or metastasis of patients with high-risk GIST.

Multimodal Imaging of Solitary Fibrous Tumor in the CNS, Head and Neck, and Spine, with Pathologic Correlation

Solitary fibrous tumor is a rare mesenchymal neoplasm arising from the serosal membranes, dura, and deep soft tissues. A solitary fibrous tumor of the CNS, head, neck, and spine can be challenging to diagnose on imaging. Preoperative consideration of a solitary fibrous tumor is critical, especially in the setting of a high-grade solitary fibrous tumor, which has a high recurrence rate and metastatic potential. This review highlights multimodal imaging features of solitary fibrous tumors, including CT, MR imaging (SWI, MRA, MRS, DWI, and perfusion), FDG PET, and catheter-directed angiography. Radiologic pathologic correlations are also provided. The management of solitary fibrous tumor is a team effort orchestrated with surgery, radiation oncology, and neurointerventional and diagnostic radiology. For high-grade solitary fibrous tumors, preoperative tumor embolization followed by surgical resection and adjuvant radiation therapy improves patient outcomes. Additional whole-body staging and follow-up MR imaging are important to evaluate recurrence or distal metastasis.Learning Objective: To recognize the multimodal imaging appearance of solitary fibrous tumor in the CNS, head and neck, and spine

Hepatocellular carcinoma: signaling pathways, targeted therapy, and immunotherapy.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a high mortality rate. It is regarded as a significant public health issue because of its complicated pathophysiology, high metastasis, and recurrence rates. There are no obvious symptoms in the early stage of HCC, which often leads to delays in diagnosis. Traditional treatment methods such as surgical resection, radiotherapy, chemotherapy, and interventional therapies have limited therapeutic effects for HCC patients with recurrence or metastasis. With the development of molecular biology and immunology, molecular signaling pathways and immune checkpoint were identified as the main mechanism of HCC progression. Targeting these molecules has become a new direction for the treatment of HCC. At present, the combination of targeted drugs and immune checkpoint inhibitors is the first choice for advanced HCC patients. In this review, we mainly focus on the cutting-edge research of signaling pathways and corresponding targeted therapy and immunotherapy in HCC. It is of great significance to comprehensively understand the pathogenesis of HCC, search for potential therapeutic targets, and optimize the treatment strategies of HCC.

Novel Flowchart Guiding the Non-Surgical and Surgical Management of Peri-Implant Complications: A Narrative Review.

Peri-implant diseases, such as peri-implant mucositis and peri-implantitis, are induced by dysbiotic microbiota resulting in the inflammatory destruction of peri-implant tissue. Nonetheless, there has yet to be an established protocol for the treatment of these diseases in a predictable manner, although many clinicians and researchers have proposed various treatment modalities for their management. With the increase in the number of reports evaluating the efficacy of various treatment modalities and new materials, the use of multiple decontamination methods to clean infected implant surfaces is recommended; moreover, the use of hard tissue laser and/or air abrasion techniques may prove advantageous in the future. Limited evidence supports additional effects on clinical improvement in antimicrobial administration for treating peri-implantitis. Implantoplasty may be justified for decontaminating the implant surfaces in the supracrestal area. Surgical treatment is employed for advanced peri-implantitis, and appropriate surgical methods, such as resection therapy or combination therapy, should be selected based on bone defect configuration. This review presents recent clinical advances in debridement methods for contaminated implant surfaces and regenerative materials for treating peri-implant bone defects. It also proposes a new flowchart to guide the treatment decisions for peri-implant disease.

P329 Sarcopenia is a risk factor of post-operative recurrence of Crohn’s disease

Abstract Background Sarcopenia is defined as reduction in skeletal muscle mass and muscle strength; it was found in up to 50% of patients with Crohn's disease (CD) in several studies.In CD patients sarcopenia is a risk factor for surgery, post-operative complications and worse surgical outcomes; furthermore, it is a negative prognostic factor for endoscopic remission in patients treated with biologics.The aim of our study was to evaluate the impact of sarcopenia on endoscopic recurrence at 6-12 months follow-up in CD patients after ileo-colic resection. Methods CD patients undergoing primary elective ileo-colic resection surgery between 2013 and 2023 were enrolled. Patients with previous intestinal surgery, pre-operative complications (abscess, perforation) and immunosuppressive or biologic therapy after surgery were excluded. Sarcopenia was defined as the sex- and height-adjusted Total Psoas Area Index (TPAI) lower than 5.4 cm2/m2 (men) and 3.56 cm2/m2 (women), calculated at the level of the third lumbar vertebra on MRI scans performed within 3 months before surgery. Already known risk factors for post-surgical disease recurrence were considered. Uni- and multi-variate analyses were performed to evaluate if sarcopenia before surgery could influence endoscopic recurrence (Rutgeers score ≥ i2) of disease 6-12 months after surgery. Results Seventy-two CD patients were included. Endoscopic recurrence (at 6-12 months follow-up colonscopy) was found in 22% of patients and it was associated with the presence of pre-operative sarcopenia (1.4% vs 15.3%;p&amp;lt;0.001) and surgical complications (2.78% vs 6.94%;p=0.024), while it was not associated with comorbidies, familiarity, smoke, extension of resection or pre-operative therapy, PCR and albumin. Sarcopenia was identify as predictor of endoscopic recurrence (OR=25;p=0.005) as well as surgical complications after resection (OR=99.7;p=0.032). Neither medical or surgical complications showed statistically significant correlation with the presence of pre-operative sarcopenia (p=0.819). Conclusion Sarcopenia in CD patients before surgery seems to be an independent prognostic factor for endoscopic recurrence. Perioperative interventions to improve sarcopenia may have positive impact on surgical outcomes and disease recurrence.

Outcomes of 3-year follow up with induction vs first line chemotherapy in oral cancer patients: An observational hospital-based study.

Our study aims to analyse and compare the efficacy, adverse effect profile and survival among the Paclitaxel/Cisplatin/5-Flurouracil (TPF) induction chemotherapy and Paclitaxel/carboplatin (PC) first line or cisplatin chemotherapy in a high-volume tertiary care cancer centre. 215 patients with oral cavity cancer were recruited in this study. Patients with stages I-IIc underwent surgical resection or radiation therapy 66-74 GY/fraction. Patients of Stages III-IV were administered with either induction chemotherapy TPF or PC or cisplatin regimen. Treatment responses were assessed by CT and MRI. Response rates, survival and adverse effects data were tabulated and analysed. The mean age was 49.2 ± 11.68 years. Symptoms were ulceration (33.5%), growth (20.5%), pain (13%), ulcer-proliferative growth (8.4%) and swelling (13, 6%). The tumour site was found at the base of the tongue, C01 (42.2%) followed by C06 (35.8%), C08 (6.5%), C07 (5.2%) and C05 (4.6%). There were no significant differences ( P > 0.05) in efficacy and survival outcomes between the different groups of treatment. Median survival was achieved within 36 months. The major side effect observed were anaemia (15.81%), diarrhoea (36.2%), dyspepsia (28.8%), fever (33.95%), mucositis (28.85%), myalgia (33.95%) and nausea (7.9%). Survival among the responder categories (CR, PR and NR) was significantly different as per Log-rank analysis ( P = 0.015). TPF induction therapy and PC first line chemotherapy showed similar efficacy, safety profile and survival whereas cisplatin shows poor efficacy and safety and survival in Indian oral cancer patients.

Zanzalintinib (XL092) plus atezolizumab versus regorafenib in previously treated MSS/MSI-low metastatic colorectal cancer (mCRC): The randomized phase 3 STELLAR-303 study.

TPS229 Background: Patients with microsatellite stable/microsatellite instability-low (MSS/MSI-low) mCRC account for ~95% of mCRC cases, and there is a significant unmet need in patients with treatment-refractory MSS/MSI-low mCRC. Although immune checkpoint inhibitors (ICIs) have shown limited activity in this patient population, the addition of tyrosine kinase inhibitors (TKIs) may increase sensitivity to ICIs by promoting an immune-permissive tumor microenvironment. Furthermore, TKI-ICI combinations have demonstrated encouraging clinical activity in patients with mCRC, particularly in subgroups of patients without liver metastases (LM). Most recently, in the phase 3 LEAP-017 study of patients with non–MSI-high/mismatch repair deficient (dMMR) mCRC, although pembrolizumab + lenvatinib did not improve overall survival (OS) vs standard of care, subgroup analysis suggested the potential for clinical benefit in patients without LM (Kawazoe et al, ESMO-WCGI 2023). Zanzalintinib is a novel multi-kinase inhibitor targeting VEGFR, MET, and the TAM kinases (TYRO3, AXL, MER). In a phase 1 study, zanzalintinib alone and in combination with atezolizumab (an anti–PD-L1 ICI) showed preliminary anti-tumor activity and a manageable safety profile across multiple tumor types (Sharma et al, ESMO 2022). Methods: STELLAR-303 (NCT05425940) is a global, randomized, open-label phase 3 study to assess the efficacy and safety of zanzalintinib + atezolizumab versus regorafenib in adult patients with MSS/MSI-low mCRC. Patients must have documented MSI/MMR status (non–MSI-high/dMMR) and RAS status by tissue-based analysis, measurable disease per RECIST v1.1, ECOG PS 0 or 1, and radiographic progression during/after or intolerance to standard of care treatments for mCRC. Prior regorafenib, trifluridine/tipiracil, or PD-L1/PD-1 ICIs are not allowed. Patients with or without active LM at baseline are eligible; those with definitively treated LM (includes surgical resection, microwave/radiofrequency ablation, or stereotactic body radiation therapy, but not yttrium-90 or chemoembolization alone) are considered to have non-active LM if treated ≥6 months before enrollment with no evidence of radiologic progression on subsequent imaging. Patients are randomized 1:1 to receive zanzalintinib + atezolizumab or regorafenib. Planned enrollment is 874 patients; number of patients with LM will be capped to ensure results of the study are relevant to the real-world mCRC population. Primary endpoint is OS in patients without LM. The key secondary efficacy endpoint is OS in all randomized patients. A hierarchical testing strategy will be employed for primary and key secondary endpoints. Safety will also be assessed. Enrollment is ongoing in the US, Europe, and Asia-Pacific region. Clinical trial information: NCT05425940 .

Comparing resection and stereotactic body radiation therapy for hepatocellular carcinoma with macrovascular invasion: A propensity score matched study.

521 Background: Macrovascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor. Current guidelines endorse systemic therapy for MVI. Local therapies present a potential for obliteration of MVI and improved survival. Surgery has been the standard local therapy at our institution, and stereotactic body radiotherapy (SBRT) has emerged as an alternative local therapy for this patient population. Methods: In this retrospective study, one-to-one optimal pair propensity score matching was used to compare outcomes of HCC patients with MVI who underwent surgery or received SBRT. Matching was done based on sex, age, ECOG, cirrhosis presence, Child-Pugh class, number of tumours, tumour volume, alpha-fetoprotein level, ALBI score, Japanese Classification of portal vein invasion, and hepatic vein invasion. Overall survival was estimated using the Kaplan-Meier method and between group differences determined using the log-rank test. The cumulative incidence of recurrence, accounting for the competing risk of death, was compared using Gray’s test. Results: Ninety of 193 patients were included after matching (45 patients in both the surgery and SBRT groups) (Table). The SBRT group had a median OS of 15 months (95% CI: 10-38), while in the surgery group it was 24 months (95% CI: 11-81). Comparing the 12-, 36-, and 60-month overall survival (OS) rates between the SBRT group (57%, 33%, 15%) and the surgery group (58%, 37%, 34%), there was no statistically significant differences (p=0.16); the 5-year OS was double in the surgical resection group. The 12-, 36-, and 60-month cumulative incidence of HCC recurrence in the SBRT group (47%, 73%, 75%) was comparable to the surgery group (69%, 69%, 69%) (p=0.89). Conclusions: Long term survival is possible in patients with HCC and MVI in a substantial minority of patients with HCC and MVI treated with local therapies. There was no statistical difference in outcomes; however, surgical resection resulted in numerically longer survival outcomes compared to SBRT after propensity score adjustment. There is rationale for investigating both local therapies with systemic therapies in future clinical trials. [Table: see text]

Non-responders to neoadjuvant chemotherapy in pancreatic adenocarcinoma: Characteristics and outcomes.

662 Background: For patients with localized pancreatic adenocarcinoma, resection and systemic therapy remain the mainstays of curative-intent treatment. Neoadjuvant chemotherapy has been frequently employed with the goals of addressing systemic disease early and improving patient selection for surgery. Those who do not respond to neoadjuvant therapy present a challenge with a lack of randomized data to aid in decision making. Here we sought to define the characteristics and outcomes of those patients to guide clinical practice. Methods: This was a single-institution retrospective cohort study using a prospectively maintained database of those diagnosed with pancreatic adenocarcinoma. Patients included in the study were those who received neoadjuvant chemotherapy. Non-responders were defined as those with both no radiographic and no biochemical response at the first re-assessment after initiation of therapy. Results: A total of 176 patients were identified who were treated with neoadjuvant chemotherapy with curative intent. Of those, 42 (23.8%) patients had no evidence of either radiographic or biochemical response. Of those patients, 14 were upfront resectable (33.3%) and 20 were borderline resectable (47.6%). An additional 8 (19%) were locally advanced. Most patients received FOLFIRINOX as a first line chemotherapy agent (n = 25, 59.5%). A total of 12 (28.6%) patients underwent neoadjuvant radiation therapy. A total of 19 (45.2%) proceeded to surgery and two of those were found to be unresectable at exploration, resulting in 17 (40.5%) who ultimately received curative-intent resection. Exactly half (n = 21) of the patients had their chemotherapy switched (CS). Of those who had CS, 11 (52.4%) had evidence of local tumor progression on their initial restaging scan compared to just 3 (14.3%) of those who did not (p = 0.02). Additionally, patients who had CS had higher incidence of vascular involvement on their initial scan (90.5% vs 52.3%, p = 0.051). A total of 6 (28.6%) who underwent CS had subsequent biochemical response compared 4 (19.0%) of those who did not. Ultimately, 6 (28.6%) of those who had CS ultimately proceeded to surgery compared to 13 (61.9%) of those who did not (p = 0.062). Interestingly, there was no significant difference in median overall survival between those who had CS (18.6 months) and those who did not (19.9 months, p = 0.525). Conclusions: Non-responders to frontline neoadjuvant systemic therapy present a clinical challenge and have poor rates of curative-intent resection. Chemotherapy switch was employed mostly in cases with worse prognostic factors and thus infrequently lead to resection. Despite this, patients who underwent CS had similar overall survival to those who did not. These data suggest there may be a role for chemotherapy switch in those who do not respond to front line chemotherapy.

Supratentorial extra-ventricular ependymoma as a mass lesion in a child: report and literature review.

Supratentorial extra-ventricular ependymoma (SEE) are extremely rare in pediatric population and have varied presentation based on size, location, epicentre and compression on neurovascular structure. The authors report a 7-year-old girl presenting with seizure, who had a lobar SEE on MRI scan, successfully treated by microsurgical resection and adjuvant therapy.

Oncological results in primary and secondary malignant chest wall tumors.

This study aims to evaluate the oncological results of primary and secondary chest wall tumors treated with curative resections and to investigate possible prognostic factors. Between January 2010 and December 2021, a total of 77 patients (53 males, 24 females; median age: 59 years; range, 3 to 87 years) who underwent curative resection for malignant chest wall tumors were retrospectively analyzed. Each tumor was staged according to its histological type. Age, sex, tumor diameter, tumor type (primary/secondary), histological tumor type, grade, stage, complete resection, rib resection, reconstruction, neoadjuvant and adjuvant therapy, recurrence, and survival data were recorded. Of the chest wall tumors, 33 (42.9%) were primary and 44 (57.1%) were secondary (local invasion, metastasis). Nine (11.7%) patients had positive surgical margins. Chest wall resection was most commonly performed due to lung cancer invasion (46.8%), followed by Ewing sarcoma (13%). Recurrence was observed in 34 (44.2%) patients. The five-year recurrence-free survival rate was 42.7% and the five-year overall survival rate was 58.6%. There was no significant difference between the primary and secondary tumors in terms of recurrence-free and overall survival (p=0.663 and p=0.313, respectively). In the multivariate analysis, tumor grade and rib resection were found to be independent prognostic factors for both recurrence-free survival (p=0.005 and p<0.001, respectively) and overall survival (p=0.048 and p=0.007, respectively). Successful oncological results can be achieved in wellselected patients with primary and secondary chest wall tumors. The grade of the tumor should be taken into account while determining the neoadjuvant or adjuvant treatment approach and surgical margin width. Rib resection should not be avoided when necessary.

The Role of Radiotherapy for Meningeal Melanocytomas - A 20 Year Update.

Meningeal melanocytomas are rare tumors of the central nervous system and optimal treatment needs further clarification. This study compared subtotal resection (STR), STR plus radiation therapy (RT), gross total resection (GTR), and GTR+RT to better define the role of postoperative RT. All cases reported in the literature were reviewed. Patients (n=184) with complete data were analyzed for local control (LC) and overall survival (OS). On univariate analysis, GTR (vs. STR) was associated with improved LC (p=0.016). When comparing the treatment regimens, best and worst results were found after GTR+RT and STR alone, respectively (p<0.001). On univariate analysis, GTR resulted in better OS than STR (p=0.041). Moreover, the treatment regimen had a significant impact on OS (p=0.049). On multivariate analyses of LC and OS, extent of resection and treatment regimen were found to be significant factors. After STR, RT significantly improved LC but not OS. After GTR, RT did not significantly improve LC or OS. GTR was significantly superior to STR regarding LC and OS. STR+RT resulted in significantly better LC when compared to STR alone.

Prosthetic rehabilitation of unilateral midfacial defect resulting from flap related complication: A case report of clinical challenges and their solutions.

Composite defects of the head and neck region after oncologic resection are challenging and require reconstruction of several layers, including the intraoral lining, osseous reconstruction of the mandible or maxilla and soft tissue/skin coverage. Management of complications resulting from flap failure is a challenging task from a technical and aesthetic perspective that can have a substantial social and psychological impact on those affected. This clinical report describes prosthetic rehabilitation of a lateral midfacial defect and the clinical challenges encountered and their solutions in a patient with carcinoma of gingivobuccal complex who underwent composite bite resection, reconstruction and adjuvant radiation therapy. A conventional approach that employed an acrylic substructure and silicone (one-piece) prosthesis was implemented to address the cutaneous cheek defect taking into account history of recent radiotherapy and comprehensive medical history. The delivered prosthesis effectively restored the lost facial contour and concealed the facial defect, contributing to aesthetics and improving the patient's quality of life.

Modularized supramolecular assemblies for hypoxia-activatable fluorescent visualization and image-guided theranostics.

Rationale: Molecular imaging of microenvironment by hypoxia-activatable fluorescence probes has emerged as an attractive approach to tumor diagnosis and image-guided treatment. Difficulties remain in its translational applications due to hypoxia heterogeneity in tumor microenvironments, making it challenging to image hypoxia as a reliable proxy of tumor distribution. Methods: We report a modularized theranostics platform to fluorescently visualize hypoxia via light-modulated signal compensation to overcome tumor heterogeneity, thereby serving as a diagnostic tool for image-guided surgical resection and photodynamic therapy. Specifically, the platform integrating dual modules of fluorescence indicator and photodynamic moderator using supramolecular host-guest self-assembly, which operates cooperatively as a cascaded "AND" logic gate. First, tumor enrichment and specific fluorescence turn-on in hypoxic regions were accessible via tumor receptors and cascaded microenvironment signals as simultaneous inputs of the "AND" gate. Second, image guidance by a lighted fluorescence module and light-mediated endogenous oxygen consumption of a photodynamic module as dual inputs of "AND" gate collaboratively enabled light-modulated signal compensation in situ, indicating homogeneity of enhanced hypoxia-related fluorescence signals throughout a tumor. Results: In in vitro and in vivo analyses, the biocompatible platform demonstrated several strengths including a capacity for dual tumor targeting to progressively facilitate specific fluorescence turn-on, selective signal compensation, imaging-time window extension conducive to precise normalized image-guided treatment, and the functionality of tumor glutathione depletion to improve photodynamic efficacy. Conclusion: The hypoxia-activatable, image-guided theranostic platform demonstrated excellent potential for overcoming hypoxia heterogeneity in tumors.