Translational insights into the genetics and immunobiology of relapsed/refractory follicular lymphoma.

Although follicular lymphoma (FL) is traditionally classified as an indolent subtype of B cell non-Hodgkin lymphoma, clinical trajectories are often diverse based on unique disease biology, and many patients will eventually experience relapse of their disease. Furthermore, progression of disease within 24 months is associated with increased mortality rates for FL. In the last five years, we have witnessed an upsurge in the commercial availability of targeted therapies for relapsed/refractory (R/R) FL, including chimeric antigen receptor-T (CAR-T) products, bispecific T cell engagers (BiTEs), epigenetic modifier therapies, and next-generation Bruton tyrosine kinase (BTK) inhibitors. Furthermore, clinical trial options have increased tremendously and now include combinatorial strategies that exert synergy against malignant germinal center B cells. Here, we provide a 2024 update of novel therapeutic agents whose development has been informed by recent advances in the genetics and immunobiology of R/R FL. Specifically, we emphasize high-value targeted therapeutics, including anti-CD3 x anti-CD20 BiTEs and adoptive T cell therapies. We discuss prospects on selection and sequencing of BiTEs and CAR-T therapies for patients with R/R FL. We underscore the principles of FL pathobiology that are paving way for future drug discovery and shed insight into therapeutic targeting within nodal basins based on our increasing understanding of the FL microenvironment. Finally, we summarize how a greater knowledge of FL immunobiology can inform risk stratification and therapy selection on a personalized basis for R/R FL in 2025.

Improving compliance with appropriateness of testing for heparin-induced thrombocytopaenia: a quality improvement report.

Heparin-induced thrombocytopaenia (HIT) is a serious complication of heparin therapy. Evidence-based guidelines recommend the use of the 4Ts scoring system to calculate pretest probability of HIT. However, this scoring system is often underused, and inappropriate testing can lead to increased morbidity, medical costs and length of hospital stay. We identified that inappropriate testing for HIT was common at our institution and implemented structured multicomponent educational interventions to evaluate the impact of education on the appropriateness of HIT testing. The educational interventions led to a significantly increased rate of appropriateness of HIT testing (69% vs 35%; p=0.001). In addition, the 4Ts score documentation rate significantly improved following the intervention (52% vs 17%; p=0.001). The rates of discontinuation of heparin products and initiation of alternative anticoagulation increased, although not statistically significantly. Educational interventions can improve compliance with evidence-based guidelines on appropriateness of testing for HIT.

COVID-19's Impact on Cancer Care: Increased Emotional Stress in Patients and High Risk of Provider Burnout.

BACKGROUND: COVID-19's precise impact on cancer patients and their oncologic care providers remains poorly understood. This study aims at comparatively analyzing COVID-19's effect on cancer care from both patient and provider perspectives. METHODS: A multi-institutional survey was developed to assess COVID-19-specific concerns regarding treatment, safety, and emotional stress through 5-point Likert-type prompts and open-ended questions before and during the pandemic. Wilcoxon signed-rank and rank-sum tests were used to analyze before/during answers for providers and patients independently. Open-ended responses were assessed using inductive thematic analysis. RESULTS: The survey was completed by 104 (69.3%) patients and 50 (50%) providers. Patients demonstrated a significant change in only 1 of 15 Likert prompts. Most significant were increased concern regarding susceptibility to infection [z = 2.536, p = 0.011] and concerns regarding their cancer outcome [z = 4.572, p < 0.001]. Non-physician providers demonstrated significant change in 8 of 13 Likert prompts, whereas physicians had all 13 Likert prompts change in the COVID-19 setting. Physicians believed care to be more poorly planned [z = -3.857, p ≤ 0.001], availability of protective personal equipment to be more limited [z = -4.082, p < 0.001], and were significantly concerned infecting family members [z = 4.965, p < 0.001]. CONCLUSIONS: While patients had more difficulty coping with their cancer, they did not perceive significant differences in their actual treatment. This suggests the need for a renewed focus on patients coping with cancer. Among providers, physicians more than any other provider group had a strong negative perception of COVID-19's impact on healthcare, suggesting the need for novel approaches to target physician burnout.

Outcomes of metastatic urothelial carcinoma following discontinuation of enfortumab-vedotin.

BACKGROUND: Enfortumab vedotin (EV) is approved to treat metastatic urothelial carcinoma (mUC) following platinum and PD1/L1 inhibitors. Since the outcomes and patterns of therapy of patients following discontinuation of EV are unknown, we conducted a retrospective study to assess this issue. METHODS: Data were retrospectively obtained from patients with mUC following discontinuation of EV after prior platinum-based chemotherapy and PD1/L1 inhibitors. Objective response rate (ORR) was evaluated in those who received therapy post-EV. Statistical analyses were performed to describe the overall survival (OS) and compare patient characteristics and outcomes of those who did or did not receive treatment post-EV. RESULTS: Data were available for 63 patients from 6 institutions: 46 (73%) were male and median age was 68 years (range 43-83). The median OS was 32 weeks. Thirty-two patients (51%) received therapy after EV. The OS of those who did vs. did not receive post-EV therapy was significantly different (median 43.1 vs. 16.9 weeks, P = .015). Longer duration of prior EV therapy was associated with receipt of post-EV therapy (P = .0437) as well as OS in both the treated (P = .045) and untreated groups (P = .012). Objective response was observed in 3 of 32 patients (9.4%) who received therapy post-EV. CONCLUSION: Outcomes of patients with mUC following discontinuation of EV are dismal and only 51% received therapy after discontinuation of EV. This study identifies benchmarks for the interpretation of activity of new agents following EV and raises the hypothesis for duration of EV as a potential prognostic factor following discontinuation of EV.

Selection criteria for minimally invasive resection of intrahepatic cholangiocarcinoma-a word of caution: a propensity score matched analysis using the national cancer database.

BACKGROUND: While minimally invasive liver resection (MILR) vs. open approach (OLR) has been shown to be safe, the perioperative and oncologic safety for intrahepatic cholangiocarcinoma (ICC) specifically, necessitating often complex hepatectomy and extended lymphadenectomy, remains ill-defined. METHODS: The National Cancer Database was queried for patients with ICC undergoing liver resection from 2010 to 2016. After 1:1 Propensity Score Matching (PSM), Kruskal-Wallis and χ2 tests were applied to compare short-term outcomes. Kaplan-Meier survival analyses and Cox multivariable regression were performed. RESULTS: 988 patients met inclusion criteria: 140 (14.2%) MILR and 848 (85.8%) OLR resulting in 115 patients MILR and OLR after 1:1 PSM with c-index of 0.733. MILR had lower unplanned 30-day readmission [OR 0.075, P = 0.014] and positive margin rates [OR 0.361, P = 0.011] and shorter hospital length of stay (LOS) [OR 0.941, P = 0.026], but worse lymph node yield [1.52 vs 2.07, P = 0.001]. No difference was found for 30/90-day mortality. Moreover, multivariate analysis revealed that MILR was associated with poorer overall survival compared to OLR [HR 2.454, P = 0.001]. Subgroup analysis revealed that survival differences from approach were dependent on major hepatectomy, tumor size > 4 cm, or negative margins. CONCLUSION: MILR vs. OLR is associated with worse lymphadenectomy and survival in patients with ICC greater than 4 cm requiring major hepatectomy. Hence, MILR major hepatectomy for ICC should only be approached selectively and if surgeons are able to perform an appropriate lymphadenectomy.

Poorly differentiated hepatocellular carcinoma: resection is equivalent to transplantation in patients with low liver fibrosis.

BACKGROUND: Organ allocation criteria for liver transplantation focus on tumor size and multifocality while tumor differentiation and existing liver damage are omitted. This study analyzes the impact of hepatocellular carcinoma (HCC) grade and liver fibrosis comparing resection (SX) to transplantation (LT). METHODS: The National Cancer Database was queried between 2004 and 2016 for solitary HCC meeting Milan criteria undergoing SX vs LT. Two groups were created: low fibrosis (LF) vs high fibrosis (HF) and stratified by grade. Cox multivariable regression models, Kaplan-Meier survival analyses and log-rank tests were performed. RESULTS: 1515 patients were identified; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months; LT mOS was 47.9 months vs SX mOS of 34.9 months (P < .001). Multivariate analysis revealed SX, no chemotherapy, longer hospital stays, and age to be associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, SX vs LT did not impact survival for poorly differentiated HCC in LF patients, independent of tumor size. DISCUSSION: HCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vs LT. Therefore, current HCC transplantation criteria should incorporate tumor grade or liver fibrosis for optimal organ allocation.

Does a Laparoscopic Approach to Distal Pancreatectomy for Cancer Contribute to Optimal Adjuvant Chemotherapy Utilization?

BACKGROUND: Although laparoscopic distal pancreatectomy (LDP) versus open approaches (ODP) for pancreatic adenocarcinoma (PDAC) is associated with reduced morbidity, its impact on optimal adjuvant chemotherapy (AC) utilization remains unclear. Furthermore, it is uncertain whether oncologic resection quality markers are equivalent between approaches. METHODS: The National Cancer Database (NCDB) was queried between 2010 and 2016 for PDAC patients undergoing DP. Effect of LDP vs ODP and institutional case volumes on margin status, hospital stay, 30-day and 90-day mortality, administration of and delay to AC, and 30-day unplanned readmission were analyzed using binary and linear logistic regression. Cox multivariable regression was used to correct for confounders. RESULTS: The search yielded 3411 patients; 996 (29.2%) had LDP and 2415 (70.8%) had ODP. ODP had higher odds of readmission [odds ratio (OR) 1.681, p = 0.01] and longer hospital stay [ß 1.745, p = 0.004]. No difference was found for 30-day mortality [OR 1.689, p = 0.303], 90-day mortality [OR 1.936, p = 0.207], and overall survival [HR 1.231, p = 0.057]. The highest-volume centers had improved odds of AC [OR 1.275, p = 0.027] regardless of approach. LDP conferred lower margin positivity [OR 0.581, p = 0.005], increased AC use [3rd quartile: OR 1.844, p = 0.026; 4th quartile; OR 2.144, p = 0.045], and fewer AC delays [4th quartile: OR 0.786, p = 0.045] in higher-volume centers. CONCLUSIONS: In selected patients, LDP offers an oncologically safe alternative to ODP for PDAC independent of institutional volume. However, additional oncologic benefit due to optimal AC utilization and lower positive margin rates in higher volume centers suggests that LDP by experienced teams can achieve best possible cancer outcomes.

Indocyanine green staining for intraoperative perfusion assessment.

Indocyanine green (ICG) is a fluorescent iodide-based dye which is used in hepatic surgery to evaluate the biliary tree, liver perfusion, and function. While liver perfusion assessment and delineation of anatomic regions has been performed using ultrasound, ischemic demarcation, or indigo carmine/methylene blue staining, ICG staining can overcome limitations associated with these techniques, such as rapid washout, lack of precision, non-demarcation in damaged livers, and lack of intraparenchymal fidelity. ICG can be used to fluoresce target segments/tumors (Positive staining) or counterstain normal liver tissue leaving areas of interest unstained (negative staining). Moreover, ICG enhancement patterns vary for different tumors, such as colorectal liver metastases vs. hepatocellular carcinoma, providing not only help with detection but also assessment of differentiation. In the field of oncology, benefits of ICG include detection of small radiographically occult tumors, distinction between cirrhotic nodules and cancer, identification of necrotic tumors in chemotherapy-damaged livers, and determining margins when intraoperative ultrasound is inadequate. While ICG has important and expanding indications in hepatic surgery, limitations include small depth of penetrance, need for special monitors/equipment, and potential for dye spillage. ICG is well tolerated, has a small learning curve, minimally invasive surgical integration, and options of both portal vein and peripheral vein injection and hence is a safe and versatile method of anatomic liver mapping, tumor visualization, and liver graft perfusion evaluation in oncologic surgery and liver transplantation. Advancements in technique and technology associated with ICG will aid in increasing the indications in hepato-biliary surgery.

Clinical Prognosticators of Metastatic Potential in Patients with Small Pancreatic Neuroendocrine Tumors.

BACKGROUND: While observation of T1(≤2cm) nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs) is an accepted practice, an ill-defined subgroup of patients with T1 tumors develops metastases. This study aimed to identify those patients via clinical factors. METHODS: Patients from the Surveillance, Epidemiology, and End Results (SEER) registry who were diagnosed with NF-PanNET with size ≤2cm between 1998 and 2014 and who underwent primary tumor resection were identified. Binary logistic regression analyses were performed to evaluate factors associated with pathological nodal and systemic metastatic disease. RESULTS: A total of 612 patients with T1 NF-PanNETs were identified. Of those, 72 (11.7%) developed nodal metastasis and 35 (5.7%) distant metastasis (M1). In the multivariable analysis, tumor location in the pancreatic body (OR 1.903, p=0.03) (OR 1.407, p=0.038) or tail (OR 1.258, p=0.04) (OR 1.612, p=0.021); tumor grade III-IV (OR 2.042, p=0.022) (OR 5.379, p≤0.001); and younger age (OR 0.963, p=0.01) (OR 0.919, p=0.009) were associated with nodal metastases and the presence of M1 disease, respectively. CONCLUSION: While the low metastatic potential of ≤2cm NF-PanNET implies watchful waiting to be an appropriate strategy for most patients, the increased risk of metastatic disease in younger patients with high grade (III-IV) body/tail tumors suggests individualized risk stratification to be optimal.

Delayed presentation of doxorubicin extravasation into pleural space: Case report and review of literature.

INTRODUCTION: Intrathoracic extravasation of anthracyclines is a dangerous and very rare complication of chemotherapy administration. While management of extravasation into soft tissues has been established, the data on treatment of mediastinal and intrapleural anthracycline extravasation is limited. CASE REPORT: We present a case of a 52-year-old woman with intrapleural doxorubicin extravasation who presented to the hospital 24-hrs after chemotherapy infusion with chest pain and shortness of breath. MANAGEMENT & OUTCOME: The patient underwent urgent surgical intervention and received IV dexrazoxane 36-hrs after the event. Her pain improved, but she continued to have chest soreness and pleural effusion at the site of extravasation even 3 months later. DISCUSSION: We conducted review of literature using Medline/PubMed and Google Scholar databases and identified 7 cases of intrapleural and mediastinal anthracycline extravasation. No data is currently available regarding the outcome of delayed management of intrapleural anthracycline extravasation with dexrazoxane. Prevention and confirmation of adequate port catheter placement is the most important step to avoid such cases. Catheter misplacement should be suspected in any patient presenting with post procedural chest pain and should trigger a thorough evaluation prior to any chemotherapy administration.

Right and Left-Sided Carcinoid Heart Disease in the Setting of Selective Serotonin Reuptake Inhibitor Use.

Carcinoid heart disease is a complication of carcinoid syndrome. The role of selective serotonin reuptake inhibitors in carcinoid heart disease is unclear. We present a case of refractory heart failure due to right- and left-sided carcinoid heart disease in the setting of selective serotonin reuptake inhibitor use despite remission of carcinoid syndrome. (Level of Difficulty: Beginner.).

Multimodality therapy of endometrial glassy cell carcinoma: a rare type of cancer.

Glassy cell carcinoma (GCC) is a rare histologically aggressive cancer subtype of the cervix that is associated with poor prognosis. Only 16 cases of endometrial GCC (EGCC) have been described in the literature to date. The data on prognostic factors and management of EGCC are limited and no optimal treatment protocol has been established. We describe a case of a 67-year-old woman who presented with postmenopausal bleeding and was diagnosed with stage IA EGCC. The patient's risk factors included histology, age and lower uterine segment involvement. The patient was successfully treated with total hysterectomy and bilateral salpingo-oophorectomy with pelvic node dissection followed by adjuvant sandwich chemotherapy and radiotherapy. The patient has no evidence of disease recurrence for 18 months. This is the first case of EGCC management with adjuvant multimodality therapy.

ROS1-rearranged lung adenocarcinoma with peritoneal carcinomatosis on initial presentation.

Peritoneal carcinomatosis (PC) is progression of the primary cancer to the peritoneum that is seen in only 1.2% of patients with lung cancer. It is associated with poor prognosis especially if present at the time of initial cancer diagnosis. The predisposing factors for peritoneal spread are not yet well understood. It has been suggested that the oncogene status of the tumour can influence the patterns of metastatic spread. There is not enough data about the role of c-ROS oncogene 1 (ROS1) mutation in the development of PC in non-small cell lung cancer. Here, we describe a case of a 56-year-old man who presented with new-onset ascites and was found to have PC. He was diagnosed with ROS1-rearranged lung adenocarcinoma. No obvious primary tumour was identified. Patient responded well to targeted therapy with crizotinib and remained 6 months free of disease progression.

Regional metastatic paraganglioma of the bladder: a rare cause of myocardial infarction, reversible cardiomyopathy and an intracardiac thrombus.

Sympathetic paragangliomas are rare neuroendocrine tumours that arise from chromaffin cells and secrete catecholamines. On rare occasions, patients with sympathetic paragangliomas can present with symptoms of congestive heart failure. The optimal treatment is surgical to remove all disease and thereby improve survival as well as restore cardiac function. We report a case of a patient with a regional metastatic bladder paraganglioma and a succinate dehydrogenase complex subunit B gene mutation presenting with cardiomyopathy who had significant improvement in his cardiac function with surgical resection despite further progression of metastatic disease. During his 4-year follow-up period, the patient remains free from heart-failure signs and symptoms.