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This review delves into the intricate landscape of pleural mesothelioma (PM), emphasizing the need for nuanced therapeutic strategies. While platinum-based chemotherapy remains a cornerstone, the advent of immune checkpoint inhibitors (ICIs), notably through the Checkmate 743 trial, has reshaped treatment paradigms. Challenges persist due to patient heterogeneity and a lack of specific biomarkers. Targeting genotypic and phenotypic alterations emerges as a promising avenue, demanding precision oncology in this rare disease. CDKN2A loss, prevalent in PM, may respond to CDK4/6 inhibitors. Defects in MMR and HR suggest tailored approaches with ICI or PARP inhibitors, respectively. Ongoing trials explore novel inhibitors and promising targets like mesothelin. Implementing these strategies requires overcoming challenges in patient selection, combination therapies, biomarker identification, and cost considerations. Collaboration is crucial for transforming these insights into impactful clinical interventions, heralding the era of personalized and precision medicine for PM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Medicaid expansion has been associated with improved access to surgical care at high-volume centers. Its impact on parathyroidectomy, however, is unclear. We evaluated the association between Medicaid expansion and parathyroidectomy at high- and low-volume centers., Methods: The Vizient Clinical Data Base was queried for parathyroidectomies. Patients were grouped by insurance status and pre- and post-Medicaid expansion periods. Hospitals were stratified into tertiles (T1-T3) by operative volume (T1 = highest-volume centers). Odds of parathyroidectomy and a difference-in-differences analysis were conducted., Results: In total, 31,983 patients were identified. Patients were predominantly privately insured (49.9%). Uninsured and Medicaid patients had increasing odds of operation at lower-tertile centers (odds ratio: T1 = ref; uninsured: T2 = 10.0, T3 = 15.8; Medicaid: T2 = 6.2, T3 = 13.5; P < .001). Medicare patients, however, were less likely to undergo operation at lower-volume centers (odds ratio: T2 = 0.89, P < .001; T3 = 0.92, P = .002). Privately insured patients were the least likely to receive care at low-volume centers (odds ratio: T3 = 0.7, P < .001). Medicaid patients in nonexpansion states had 12-16 times higher odds of parathyroidectomy at lower-volume hospitals than their counterparts in expansion states (expansion/nonexpansion states: pre-expansion T3 = 2.3/28.0; postexpansion T3 = 1.3/21.4). Expansion was associated with an increase in the proportion of parathyroidectomy for Medicaid patients, with larger gains seen at higher-volume centers (T1 = 5.0%, P = .01; T2 = 3.1%, P = .001; T3 = 2.7%, P = .03). Expansion was not associated with changes in payor distribution for uninsured, Medicare, or privately insured patients., Conclusions: Medicaid expansion was associated with an increase in parathyroidectomy for Medicaid patients at high-volume centers. However, in nonexpansion states, access to surgical treatment at high-volume centers remains limited for uninsured and underinsured patients., Competing Interests: Conflict of Interest/Disclosure The authors have no relevant conflicts of a personal or financial nature to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Integrating microRNA markers with next-generation sequencing panels may enhance risk assessment of cytologically indeterminate thyroid nodules. The ThyGeNEXT-ThyraMIRv1 multiplatform test version 1 demonstrated limited utility in risk-stratifying RAS-mutated indeterminate thyroid nodules. We sought to validate the updated ThyraMIRv2 platform in clinical practice., Methods: ThyGeNEXT/ThyraMIRv2, a 3-tiered microRNA classifier, were evaluated using a previously studied multi-institutional cohort of Bethesda III/IV nodules, with positive results having risk of malignancy ≥10%. In addition, ThyraMIRv2's clinical utility in RAS-mutated indeterminate thyroid nodules was assessed., Results: In 366 indeterminate thyroid nodules, ThyraMIRv2 platform yielded a 30.3% positive-call rate. ThyraMIRv2 platform + nodules had greater operative rates (63.9% vs 36.1%, P < .0001) and cancer/noninvasive follicular thyroid neoplasm with papillary-like nuclear features diagnosis (65.9% vs 25.0%, P < .0001) than ThyraMIRv2 platform nodules. Compared with multiplatform test version 1, ThyraMIRv2 platform's diagnostic testing parameters did not improve significantly. Among 68 RAS-mutated nodules, ThyraMIRv2 classified 36.8%, 55.9%, and 7.4% as positive, moderate, and negative, respectively. All moderate nodules had risk of malignancy ≥10% and were combined with the positive cohort. No significant differences existed in operative rate (81.0% vs 60.0%, P = .272) or cancer/noninvasive follicular thyroid neoplasm with papillary-like nuclear features diagnosis (47.6% vs 40.0%, P > .999) between RAS-mutated positive/moderate and negative groups. For RAS-mutated nodules, ThyraMIRv2 demonstrated improved sensitivity (93.8% vs 64.7, P = .003) and decreased specificity (4.5% vs 34.8%, P = .008) compared with ThyGeNEXT-ThyraMIRv1 multiplatform test version 1, with comparable negative predictive value (33.3% vs 40.0%, P = .731) and positive predictive value (58.8% vs 59.5%, P = .864)., Conclusion: ThyraMIRv2 platform does not improve indeterminate thyroid nodule malignancy stratification compared to ThyGeNEXT-ThyraMIRv1 multiplatform test version 1. ThyraMIRv2 improves malignant RAS-mutated nodule detection but increases false positives. Future studies encompassing a larger cohort of RAS-mutated with surgical pathology results are warranted to better characterize the performance parameters of this classifier., Competing Interests: Conflicts of Interest/Disclosure The authors have no potential conflicts to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The administration of proton pump inhibitors (PPIs) is a common practice to reduce gastro-esophageal adverse events associated with drug treatments but may impair absorption and exposure to oncology drugs. This study investigated the effect of concomitant administration of PPIs and pazopanib, sunitinib and cabozantinib on survival of patients with metastatic clear cell renal carcinoma (mRCC)., Patients and Methods: Total 451 patients receiving pazopanib, sunitinib and cabozantinib as first line treatment were enrolled in this retrospective study. Patients were defined as "no concomitant PPIs (PPI-)" if no PPIs were administered during TKIs, and as "concomitant PPIs (PPI+)" if the administration of PPIs was at least 75% of the time during which TKIs were given., Results: Eighty patients administered pazopanib were PPI- and 86 PPI+; no difference in PFS was observed (10.7 vs. 11.9 months, P = .79). If patients were stratified as short (n = 89) and long (n = 77) responders, there was a significant difference in terms of PFS in PPI+ (n = 47) versus PPI- (n = 30) in long responders, being 24.7 versus 38 months (P = .04), respectively. In the sunitinib cohort, no significant difference of PFS in PPI+ (n = 102) versus PPI- (n = 131) was found, being 11.3 versus 18.1 months, respectively (P=0.15). In the cabozantinib cohort, there was a statistically significant difference in PFS of PPI+ versus PPI- (6 months vs. not reached, P = .04). No correlation with adverse events was found., Conclusions: This study demonstrates an association between PPIs and impaired PFS in mRCC patients given pazopanib and cabozantinib and recommends caution on their concomitant use., Competing Interests: Disclosure CP acted as a consultant and/or a speaker for Angelini Pharma, Biorek, BMS, Eisai, General Electric, Ipsen, Medendi, and MSD, and as a protocol steering committee member for BMS, Eisai, and MSD. MR received honoraria as a speaker/consultant by Astra Zeneca, MSD, BMS, Janssen, Merck and Gilead. MDR received fees from Astellas, AstraZeneca, Celgene, Novartis, Pfizer, Bio-Rad, Janssen, Sanofi-Aventis, Roche, and Ipsen; RD reports receiving speaker bureau/advisor's fee from Ipsen, Novartis, Pfizer, Sanofi Genzyme, AstraZeneca, Janssen, Gilead, Lilly, Gilead, and EUSA Pharma. All other authors have declared no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Several anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have been developed for the treatment of echinoderm microtubule-associated protein-like 4 (EML4)-ALK-rearranged non-small cell lung cancer (NSCLC), with the newer generation agents brigatinib, alectinib and lorlatinib showing prolonged responses. With the increasing number of target therapies available, the optimal sequence is yet to be defined, as resistance profiles may evolve over time and in response to sequential ALK inhibitors. Therefore, ALK-targeted strategies may be personalized based upon the presence of specific ALK resistance mutations., Methods: Here, we report on the case of a patient who has been treated with a sequence of three ALK TKIs after receiving diagnosis of ALK-rearranged metastatic NSCLC in 2015 and gained further benefit upon lorlatinib rechallenge after the acquisition of the G1202R resistance mutation to second generation TKIs., Results and Conclusion: In this case, the first ALK resistance mutation detected after progression on first line TKI, the I1171N, is a common resistance mutation after alectinib and confers sensitivity to brigatinib, that the patient received afterwards with a long-term disease stability. The second ALK resistance mutation detected after a chemotherapy interval, the G1202R, is the most common resistance mutation after second generation ALK TKIs and has been associated with sensitivity to third generation TKIs, such as lorlatinib. This case of a patient with EML4-ALK-rearranged NSCLC shows that sequential treatment with next-generation ALK TKIs, including rechallenge, can induce profound remissions, even in heavily pretreated patients, and that ALK-targeted strategies may be personalized by considering the presence of distinct ALK resistance mutations., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The 2015 American Thyroid Association (ATA) guidelines recommended thyroid lobectomy (TL) as an alternative to total thyroidectomy (TT) for the surgical treatment of low-risk differentiated thyroid cancer. Increasing use of TL has since been reported despite concerns for an increased risk of disease recurrence and need for reoperation. This study sought to compare reoperation rates among patients who underwent initial TL or TT for malignancy, characterize trends at centers based on operative volume, and examine factors associated with reoperation. Methods: We queried the Vizient Clinical Data Base for TL and TT performed preguideline change (pre-GC = 2013-2015) and postguideline change (post-GC = 2016-2021). Reoperations included reoperative thyroid surgery (RTS) and neck dissection (ND); timing was defined as early (≤180 days), thought to indicate inadequacy of initial operative choice, or late (>180 days), suggesting potential disease recurrence. Results: Of 65,627 patients, 31.8% underwent initial TL and 68.2% underwent initial TT; TL increased from 21.4% of total cases pre-GC to 37.0% post-GC ( p < 0.001). Among TL patients, early RTS declined from 33.9% to 14.2% and ND declined from 0.8% to 0.4% ( p < 0.001). Among TT patients, early RTS remained 0.2%, while ND increased from 0.4% to 0.7% ( p < 0.001). TL-associated late RTS declined from 2.0% to 1.7%, while ND increased from 0.6% to 0.8% ( p = 0.17). In TT patients, both late RTS and ND increased, from 0.2% to 0.3% ( p = 0.04) and 1.7% to 2.1% ( p < 0.01), respectively. There was no difference in the late reoperation rate for TL compared with TT post-GC (+0.2%, p = 0.18). TL volume grew annually by 12.5% [8.9-16.2%] at high-volume centers (HVCs) and 8.3% [5.6-11.1%] at low-volume centers (LVCs). TL-associated reoperations at HVCs declined annually by 12.6% [5.6-19.0%] and 10.8% [2.7-18.1%] at LVCs. Uninsured status and more recent initial operation were associated with an increased risk of late reoperation (HR = 1.84 [1.06-3.20] and HR = 1.30 [1.24-1.36], respectively). The type of index operation performed, however, was not predictive of late reoperation. Conclusions: The rate of early reoperations declined for TL after the 2015 ATA guideline release, but late reoperations remained unchanged despite a significant shift in practice patterns towards initial lobectomy. Patients appear to be receiving less aggressive, guideline-concordant care without a significant increase in the late reoperation rate for TL compared with TT.

Background: The COVID-19 pandemic disrupted routine health care, including many elective and non-cancer operations in the United States. Most hepato-pancreato-biliary malignancy patients require outpatient imaging, tissue sampling, and staging, and many undergo neoadjuvant therapy before operative intervention. The aims of this study were to evaluate the effect of the COVID-19 pandemic on hepato-pancreato-biliary oncologic operations and to determine whether trends in neoadjuvant therapy were altered by the pandemic., Methods: Adult patients in the United States undergoing oncologic operations for pancreatic, primary and secondary hepatic malignancies, with or without neoadjuvant therapy, were extracted from the Vizient Clinical Data Base. Control chart analysis was used to plot trends over time and to determine whether changes were statistically significant. Wilcoxon rank-sum tests also compared monthly operative volume from pre-pandemic (12 month) and pandemic (28 months) periods., Results: A total of 36,553 patients were identified over 40 months. Mean monthly pancreatic oncologic operations were unaffected by the pandemic (P = .257). Operations for pancreatic oncologic operations with prior neoadjuvant therapy increased throughout the pandemic (P = .002). Oncologic operations for primary and secondary hepatic malignancies were significantly reduced for 4 and 2 months, respectively, at the beginning of the pandemic but returned to their pre-pandemic baseline within 4 months (P = .169 and P = .598)., Conclusion: Pancreatic operation volumes for cancer did not change, but pancreatic operations after neoadjuvant therapy continued to increase during the pandemic. Operations for hepatic malignancy were transiently disrupted but quickly normalized. These observations suggest that surgery for hepato-pancreato-biliary malignancies was prioritized during the pandemic., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Insurance-based disparities in access to thyroidectomy are well established. Patients undergoing thyroidectomy by high-volume surgeons have fewer complications and better postoperative outcomes. The aim of this study was to evaluate the association of Medicaid expansion with access to high-volume centers for thyroidectomy for benign disease., Methods: The Vizient Clinical Data Base was queried for adult operations for benign thyroid disease from 2010 to 2019. Centers were sorted by volume into quartiles. Difference-in-difference analysis evaluated changes in insurance populations in expansion and non-expansion states after Medicaid expansion. Odds of patients undergoing operations in the 4 volume quartiles after stratifying by insurance and Medicaid expansion status were calculated., Results: A total of 82,602 patients underwent operations at 364 centers. Expansion states increased Medicaid coverage in all volume quartiles compared to non-expansion states after Medicaid expansion (Q1, +4.87%, Q2, +5.35%, Q3, +8.57%, Q4, +4.62%, P < .002 for all). After Medicaid expansion, Medicaid patients had higher odds of undergoing operation at lower volume hospitals compared to the highest volume centers in both expansion states (Q1, ref, Q2, 1.82, Q3, 1.76, Q4, 1.67, P < .001) and non-expansion states (Q1, ref, Q2, 1.54, Q3, 2.04, Q4, 1.44, P < .001). Privately insured patients were most likely to undergo their operation at the highest volume centers in all states (E: Q1, ref, Q2, 0.78, Q3, 0.74, Q4, 0.66, P < .001; NE: Q1, ref, Q2, 0.89, Q3, 0.58, Q4, 0.85, P < .001)., Conclusion: Medicaid expansion increased Medicaid coverage in expansion states, but Medicaid patients in both expansion and non-expansion states were less likely to be operated on at the highest volume centers compared to privately insured patients. Persistent barriers to accessing high-volume care still exists for Medicaid patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The 2015 American Thyroid Association guidelines recommend lymph node mapping US in patients with definitive cytological evidence of thyroid cancer. Suspicious lymph node features on imaging including enlarged size (>1 cm in any dimension), architectural distortion, loss of fatty hilum, and microcalcifications often prompt evaluation with fine needle aspiration. There is no universally agreed upon model for determining which ultrasound characteristics most strongly correlate with metastatic disease., Methods: A retrospective review of patients with confirmed papillary thyroid cancer (PTC) undergoing lymph node mapping ultrasound from 2013 to 2019 was performed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for each individual ultrasound characteristic as well as for characteristic combinations., Results: Data from 119 lymph nodes were included. Malignant lymph nodes were more likely to be enlarged (71% versus 61%, P < 0.001) and to have each individual suspicious feature. Loss of fatty hilum had the highest sensitivity (89%) but was not specific (19%) for metastatic disease. Architectural distortion was found to have the highest specificity (87%). A combination of the four features was found to have higher specificity (97%) and PPV (88%) than any individual feature or combination of two/three features., Conclusions: A combination of four sonographic features correlates with metastatic PTC to lymph nodes and has the highest specificity and PPV for malignancy. A risk stratification model based on these features may lead to better classification of ultrasound findings in PTC patients with concern for nodal metastases., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Mucinous appendiceal adenocarcinomas (MAA) and non-mucinous appendiceal adenocarcinomas (NMAA) demonstrate differences in rates and patterns of recurrence, which may inform the appropriate extent of surgical resection (i.e., appendectomy versus colectomy). The impact of extent of resection on disease-specific survival (DSS) for each histologic subtype was assessed., Patients and Methods: Patients with resected, non-metastatic MAA and NMAA were identified in the Surveillance, Epidemiology, and End Results database (2000-2020). Multivariable models were created to examine predictors of colectomy for each histologic subtype. DSS was calculated using Kaplan-Meier estimates and examined using Cox proportional hazards modeling., Results: Among 4674 patients (MAA: n = 1990, 42.6%; NMAA: n = 2684, 57.4%), the majority (67.8%) underwent colectomy. Among colectomy patients, the rate of nodal positivity increased with higher T-stage (MAA: T1: 4.6%, T2: 4.0%, T3: 17.1%, T4: 21.6%, p < 0.001; NMAA: T1: 6.8%, T2: 11.4%, T3: 25.6%, T4: 43.8%, p < 0.001) and higher tumor grade (MAA: well differentiated: 7.7%, moderately differentiated: 19.2%, and poorly differentiated: 31.3%; NMAA: well differentiated: 9.0%, moderately differentiated: 20.5%, and 44.4%; p < 0.001). Nodal positivity was more frequently observed in NMAA (27.6% versus 16.4%, p < 0.001). Utilization of colectomy was associated with improved DSS for NMAA patients with T2 (log rank p = 0.095) and T3 (log rank p = 0.018) tumors as well as moderately differentiated histology (log rank p = 0.006). Utilization of colectomy was not associated with improved DSS for MAA patients, which was confirmed in a multivariable model for T-stage, grade, and use of adjuvant chemotherapy [hazard ratio (HR) 1.00, 95% confidence interval (CI) 0.81-1.22]., Conclusions: Colectomy was associated with improved DSS for patients with NMAA but not MAA. Colectomy for MAA may not be required., (© 2024. The Author(s).)

Introduction: The tall cell, columnar, and diffuse sclerosing subtypes are aggressive histologic subtypes of papillary thyroid cancer (PTC) with increasing incidence, yet there is a wide variation in reporting. We aimed to identify and compare factors associated with the reporting of these aggressive subtypes (aPTC) to classic PTC (cPTC) and secondarily identify differences in outcomes., Methods: The National Cancer Database was utilized to identify cPTC and aPTC from 2004 to 2017. Patient and facility demographics and clinicopathologic variables were analyzed. Independent predictors of aPTC reporting were identified and a survival analysis was performed., Results: The majority of aPTC (67%) were reported by academic facilities. Compared to academic facilities, all other facility types were 1.4-2.0 times less likely to report aPTC (P < 0.05). Regional variation in reporting was noted, with more cases reported in the Middle Atlantic, despite there being more total facilities in the South Atlantic and East North Central regions. Compared to the Middle Atlantic, all other regions were 1.4-5 times less likely to report aPTC (P < 0.001). Patient characteristics including race and income were not associated with aPTC reporting. Compared to cPTC, aPTC had higher rates of aggressive features and worse 5-y overall survival (90.5% versus 94.5%, log rank P < 0.001)., Conclusions: Aggressive subtypes of PTC are associated with worse outcomes. Academic and other facilities in the Middle Atlantic were more likely to report aPTC. This suggests the need for further evaluation of environmental or geographic factors versus a need for increased awareness and more accurate diagnosis of these subtypes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Racial and ethnic disparities have been observed in the multidisciplinary management of pancreatic ductal adenocarcinoma. Intraductal papillary mucinous neoplasm is the most common identifiable precursor to pancreatic ductal adenocarcinoma, where early surgical intervention before the development of an invasive intraductal papillary mucinous neoplasm improves survival. The association of race/ethnicity with the risk of identifying invasive intraductal papillary mucinous neoplasms during resection has not been previously defined., Methods: The American College of Surgeons National Quality Improvement Program targeted pancreatectomy database (2014-2021) was queried for patients with race/ethnicity data who underwent resection of an intraductal papillary mucinous neoplasm. Backward Wald logistic regression modeling (P ≤ 0.05 for entry; P > .10 for removal) was used to identify independent predictors of invasion., Results: A total of 4,505 cases of resected intraductal papillary mucinous neoplasms were identified, with 923 (20.5%) demonstrating invasive intraductal papillary mucinous neoplasms. The cohort of individuals other than non-Hispanic Whites were significantly more likely to have invasive intraductal papillary mucinous neoplasms (White, 19.9%; Black, 24.2%; Asian, 23.7%; Hispanic, 22.6%; P = .026). Such disparity could not be explained by greater comorbidity, as non-White patients were significantly younger (age <65 years: 41.7% vs 33.2%, P < .001) and had better physical status (American Society of Anesthesiologists score ≤2: 28.8% vs 25.2%, P = .053). After controlling for clinicodemographic variables, being an individual of race/ethnicity other than White was independently associated with higher odds of invasive intraductal papillary mucinous neoplasms (odds ratio, 1.280; 95% confidence interval, 1.046-1.566; P = .017). No differences in postoperative morbidity were observed., Conclusion: In a national cohort of patients with resected intraductal papillary mucinous neoplasms, individuals who identified as being of race/ethnicity other than White were significantly more likely to have invasive intraductal papillary mucinous neoplasms during surgical resection., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)