Evaluation for primary hyperparathyroidism after radioactive iodine treatment in patients with Graves' disease.

BACKGROUND: Retrospective studies are conflicting regarding the risk of primary hyperparathyroidism after radioactive iodine treatment. We hypothesized that primary hyperparathyroidism rates are greater after radioactive iodine than after thyroidectomy and that patients with hypercalcemia after treatment for Graves' disease are not adequately evaluated for primary hyperparathyroidism, contributing to underdiagnosis of radioactive iodine-associated primary hyperparathyroidism. METHODS: This retrospective review considers patients undergoing radioactive iodine or thyroidectomy for Graves' disease at a tertiary referral center between January 1, 2000, and January 31, 2022. Patients were identified using a hospital-based cohort discovery tool; exclusions included history of head/neck radiation, primary hyperparathyroidism/parathyroidectomy, renal dysfunction diagnoses, or treatment with both radioactive iodine and thyroidectomy. Patients with an elevated calcium (>10.2 mg/dL) level measured after treatment were classified as "incomplete workup" (no parathyroid hormone), "likely primary hyperparathyroidism" (parathyroid hormone >40 pg/dL), or "unlikely primary hyperparathyroidism" (parathyroid hormone <40 pg/dL). RESULTS: Of 900 patients, 468 (52%) had been treated with radioactive iodine and 432 (48%) with thyroidectomy. At a median follow-up of 9.39 years (interquartile range, 5.12-13.25), 25% (n = 224) of patients did not have a serum calcium measured and 52 (8%, n = 676) patients had an elevated calcium level. Hypercalcemia was more common after radioactive iodine (10%) than thyroidectomy (6%, P = .061). Of patients with hypercalcemia, 33 (63%) were "incomplete workup," 5 (10%) were "likely primary hyperparathyroidism," and 14 (27%) were "unlikely primary hyperparathyroidism." There was no difference in primary hyperparathyroidism workup rates between patients treated with radioactive iodine (n = 23) and thyroidectomy (n = 10, P = .389). CONCLUSIONS: Patients treated with radioactive iodine for Graves' disease may experience an elevated rate of hypercalcemia, but the majority are not adequately evaluated for primary hyperparathyroidism. Patients with a history of radioactive iodine should undergo regular calcium screening and, if elevated, appropriate workup for primary hyperparathyroidism.

Patterns of Locoregional Pancreatic Cancer Recurrence After Total Neoadjuvant Therapy and Implications on Optimal Neoadjuvant Radiation Treatment Volumes.

PURPOSE: To generate a map of local recurrences after neoadjuvant chemotherapy and radiation (total neoadjuvant therapy or TNT) followed by surgical resection for pancreatic ductal adenocarcinoma (PDAC). Such recurrence patterns will serve to inform radiation treatment planning volumes that should be given in the neoadjuvant setting. METHODS: Locoregional recurrences following TNT followed by surgery treated between 2009-2022 were radiologically identified. Recurrences were individually segmented using MIM software and complied in a single base scan. All contour compilations were used to create a threshold contour encompassing 80% of recurrences among all patients, head only, and body/tail only. The distance between organs at risk and the threshold contour were measured to design an optimal clinical target volume (CTV) contour for patients treated with TNT. Recurrence patterns were also compared to existing adjuvant guidelines to assess coverage. RESULTS: A database of 484 patients managed with TNT for PDAC was queried. While locoregional recurrences were rare in this cohort, we identified eighty patients with either isolated locoregional or simultaneous local and distant recurrences. Patients with diagnostic imaging at the time of recurrence were identified. The majority of recurrences were partially in the field of published contouring guidelines or volumetric expansions off of vessels, and volumetric coverage was low for all. Common areas of recurrence include the aortico-diaphragmatic junction, retro-pancreatic duodenal nodal basin, and the region to the right of the superior mesenteric artery. A novel set of proposed neoadjuvant contours was designed to cover the central-most 80% of recurrences. CONCLUSIONS: This is the largest collection of local/regional PDAC recurrences from a cohort of patients treated exclusively with TNT. Patterns of local/regional recurrence using TNT in PDAC vary significantly from those patients with PDAC treated with a surgery-first approach. Novel contouring guidelines presented herein can help to ensure optimal coverage of high risk regions and avoid reliance on the current adjuvant guidelines to guide treatment planning.

Cosyntropin Stimulation Testing is More Selective than Postoperative Day 1 Basal Cortisol for Diagnosing Secondary Adrenal Insufficiency After Unilateral Adrenalectomy.

BACKGROUND: Secondary adrenal insufficiency (SAI) may occur in patients after unilateral adrenalectomy for adrenal-dependent hypercortisolism (HC) or primary aldosteronism (PA). This study aimed to assess whether postoperative day (POD) 1 basal cortisol was predictive of an abnormal cosyntropin stimulation test (CST) result and the need for glucocorticoid replacement (GR). METHODS: A retrospective review of consecutive patients who underwent unilateral adrenalectomy for HC, PA, or both between September 2014 and September 2022 was performed. On POD1, CST was performed for all the patients with HC, and before 2021 for all the patients with PA. The patients with an abnormal CST result were deemed at risk of SAI and discharged with GR. Receiver operating characteristic (ROC) curves were generated to evaluate the sensitivity (SN) and specificity (SP) of basal cortisol thresholds to predict an abnormal CST result. RESULTS: The patients underwent unilateral adrenalectomy for overt hypercortisolism (OH; n = 42), mild autonomous cortisol excess (MACE; n = 70), mixed PA/HC (n = 22), or PA (n = 73). On POD1, CST was performed for 152 patients (93% OH, 96% MACE,73% PA/HC, 41% PA), and 80 patients (53%) had SAI (67% OH, 55% MACE, 44% PA/HC, 33% PA). The SN and SP of a basal cortisol level of 10 µg/dL or lower to predict an abnormal CST were respectively 92% and 77% for OH, 94% and 73% for MACE, 100% and 85% for PA, and 100% and 67% for PA/HC. The optimal basal cortisol level for predicting an abnormal CST for patients with PA or PA/HC was 5 µg/dL or lower (SN/SP, 100%). CONCLUSIONS: After unilateral adrenalectomy for HC, PA, or mixed PA/HC, POD1 CST improved identification of patients at risk for SAI compared with basal cortisol levels alone. The authors recommend that POD1 CST be performed to determine the risk for SAI and the need for postoperative GR after unilateral adrenalectomy for patients with HC.

Chemotherapy-free treatment targeting fusions and driver mutations in KRAS wild-type pancreatic ductal adenocarcinoma, a case series.

Background: KRAS wild-type (WT) pancreatic ductal adenocarcinoma (PDAC) represents a distinct entity with unique biology. The therapeutic impact of matched targeted therapy in these patients in a real-world setting, to date, is less established. Objectives: The aim of our study was to review our institutional database to identify the prevalence of actionable genomic alterations in patients with KRAS-WT tumors and to evaluate the therapeutic impact of matched targeted therapy in these patients. Design: We reviewed electronic medical records of patients with KRAS-WT PDAC and advanced disease (n = 14) who underwent clinical-grade tissue ± liquid next-generation sequencing (315-648 genes for tissue) between years 2015 and 2021. Methods: Demographic and disease characteristics were summarized using descriptive parameters. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: Of 236 PDAC patients, 14 had advanced/metastatic disease with KRAS-WT tumors. Median age at diagnosis was 66 years. There was a high frequency of potentially actionable genomic alterations, including three (21%) with BRAF alterations, two (14%) with fusions [RET-PCM1 and FGFR2-POC1B (N = 1 each)]; and one with a druggable EGFR (EGFR E746_A755delISERD) variant; two other patients had an STK11 and a MUTYH alteration. Five patients were treated with matched targeted therapy, with three having durable benefit: (i) erlotinib for EGFR-altered tumor, followed by osimertinib/capmatinib when MET amplification emerged (first-line therapy); (ii) pralsetinib for RET fusion (fifth line); and (iii) dabrafenib/trametinib for BRAF N486_P490del (third line). Duration of time on chemotherapy-free matched targeted therapy for these patients was 17+, 11, and 18+ months, respectively. Conclusion: Sustained therapeutic benefit can be achieved in a real-world setting in a subset of patients with advanced/metastatic KRAS-WT PDAC treated with chemotherapy-free matched targeted agents. Prospective studies are warranted.

Surgeon compensation in academic medicine.

Academic surgery is the best career one could ever aspire to have; however, given the long duration of training and the anticipated education debt, surgeon compensation has not kept pace with the compensation of other comparable careers. As surgeon compensation has experienced increased downward pressure, it has become of growing importance to those in academic medicine/surgery. Competitive compensation is necessary, even if not sufficient, for successful faculty recruitment and retention. The optimal compensation system should encourage the best possible patient care, inspire teamwork, maximize the department's or physician practice's ability to recruit and retain faculty, support all missions, and be viewed as equitable and transparent. The goal of an optimal compensation system is to have faculty minds focused on things other than compensation-those elements of their job that are most important, such as career development, multidisciplinary clinical programs, research, and education. One way to ensure that compensation stays in the background for academic surgeons is for leadership to keep this front and center. Compensation plans can influence behavior and time management and affect the clinical, academic, and educational contributions of surgeons and physicians of all specialties. As we strive to optimize the productivity and engagement of a health system's most valuable resource-those who deliver surgical care and create new knowledge-compensation is an important variable in need of constant attention.

The Role of Demographic and Clinical Factors in Germline Mutation Testing for Patients with Primary Hyperparathyroidism.

INTRODUCTION: Guidelines recommending genetic counseling in primary hyperparathyroidism (PHPT) vary. To further delineate current recommendations, this study examined genetic counseling referral patterns and rates of mutations in surgical patients with PHPT. PATIENTS AND METHODS: A single-institution review was performed of adult patients who underwent parathyroidectomy for presumed sporadic PHPT. Genetic testing indications of hypercalcemia onset ≤ 40 years, multigland disease (MGD), family history (FHx) of PHPT, or other clinical indications suspicious for a PHPT-related endocrinopathy were examined by demographics and mutation detection rates. RESULTS: Genetic counseling was performed in 237 (37.9%) of 625 patients. Counseling was discussed but not performed in 121 (19.4%) patients. No evidence was noted of genetic referral discussion in the remaining 267 (42.7%). Of these groups, patients who received genetic counseling were youngest, p < 0.001 [median age 55.3 (IQR 43.2, 66.7) years]. The majority of patients with indications of age ≤ 40 years (65.7%), FHx (78.0%), and other clinical indications (70.7%) underwent genetic counseling, while most with MGD (57.0%) did not. Eight mutations were detected in 227 patients (3.5%). Mutations included: MEN1 (n = 2), CDC-73 (n = 4), and CASR (n = 2). Detection was most common in patients with FHx (4/71, 5.6%), then age ≤ 40 years (3/66, 4.5%), and other clinical indications (3/80, 3.8%). No mutations were identified in 48 patients tested solely for MGD. CONCLUSIONS: Most patients with onset of hypercalcemia age ≤ 40 years, positive FHx, or other clinical concerns underwent genetic counseling, while most with MGD did not. As no germline mutations were identified in patients with MGD alone, further investigation of MGD as a sole indication for genetic counseling may be warranted.

Median arcuate ligament release at the time of pancreaticoduodenectomy or total pancreatectomy.

BACKGROUND: Celiac artery compression can complicate the performance of pancreaticoduodenectomy or total pancreatectomy due to the need for ligation of the gastroduodenal artery. Median arcuate ligament release restores normal arterial flow to the liver, spleen, and stomach and may avoid complications related to poor perfusion of the foregut. METHODS: All patients who underwent median arcuate ligament release for celiac artery compression at the time of pancreatectomy between 2009 and 2023 were reviewed. Pre- and postoperative computed tomography was used to categorize celiac artery compression by the extent of compression (types A [<50%], B [50%-80%], and C [>80%]). RESULTS: Of 695 patients who underwent pancreatectomy, 22 (3%) had celiac artery compression, and a majority (17) were identified on preoperative imaging. Median celiac artery compression was 52% (interquartile range = 18); 8 (36%) patients had type A and 14 (64%) had type B compression with a median celiac artery compression of 39% (interquartile range = 18) and 59% (interquartile range = 14), respectively (P < .001). Postoperative imaging was available for 20 (90%) patients, and a reduction in the median celiac artery compression occurred in all patients: type A, 14%, and type B, 31%. Complications included 1 (5%) death after hospital discharge, 1 (5%) pancreatic fistula, 1 (5%) delayed gastric emptying, and 4 (18%) readmissions. No patient had evidence of a biliary leak or liver dysfunction. CONCLUSION: Preoperative computed tomography allows accurate identification of celiac artery compression. Ligation of the gastroduodenal artery during pancreaticoduodenectomy or total pancreatectomy in the setting of celiac artery compression requires median arcuate ligament release to restore normal arterial flow to the foregut and avoid preventable complications.

Transcriptomic-Based Microenvironment Classification Reveals Precision Medicine Strategies for Pancreatic Ductal Adenocarcinoma.

BACKGROUND & AIMS: The complex tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) has hindered the development of reliable predictive biomarkers for targeted therapy and immunomodulatory strategies. A comprehensive characterization of the TME is necessary to advance precision therapeutics in PDAC. METHODS: A transcriptomic profiling platform for TME classification based on functional gene signatures was applied to 14 publicly available PDAC datasets (n = 1657) and validated in a clinically annotated independent cohort of patients with PDAC (n = 79). Four distinct subtypes were identified using unsupervised clustering and assessed to evaluate predictive and prognostic utility. RESULTS: TME classification using transcriptomic profiling identified 4 biologically distinct subtypes based on their TME immune composition: immune enriched (IE); immune enriched, fibrotic (IE/F); fibrotic (F); and immune depleted (D). The IE and IE/F subtypes demonstrated a more favorable prognosis and potential for response to immunotherapy compared with the F and D subtypes. Most lung metastases and liver metastases were subtypes IE and D, respectively, indicating the role of clonal phenotype and immune milieu in developing personalized therapeutic strategies. In addition, distinct TMEs with potential therapeutic implications were identified in treatment-naive primary tumors compared with tumors that underwent neoadjuvant therapy. CONCLUSIONS: This novel approach defines a distinct subgroup of PADC patients that may benefit from immunotherapeutic strategies based on their TME subtype and provides a framework to select patients for prospective clinical trials investigating precision immunotherapy in PDAC. Further, the predictive utility and real-world clinical applicability espoused by this transcriptomic-based TME classification approach will accelerate the advancement of precision medicine in PDAC.

Adductor Canal Nerve Block versus Intra-articular Anesthetic in Knee Arthroscopy: A Single-Blinded Prospective Randomized Trial.

Effective perioperative pain control following knee arthroscopy allows patients to reduce narcotic intake, avoid side effects of these medications, and recover more quickly. Adductor canal nerve blockade (ACB) and intra-articular injection of local anesthetic have been described as adjuvant treatments for postoperative pain control following surgery of the knee. This study directly compares the effect of each of these treatment modalities. Patients undergoing knee arthroscopy were blinded and randomized to receive either an ACB (n = 60) or intra-articular injection of local anesthetic (IAB, n = 64). Outcome measures included patient reported visual analog scale (VAS) scores at 1, 2, 4, 8, 16, 24, 36, 48 hours and 1 week and total narcotic consumption at 12, 24, and 48 hours postoperatively. Student's t-tests were used to compare unadjusted VAS scores at each time point and use of postoperative pain medication between treatment groups. Adjusted VAS scores were estimated in a multivariable general linear model with interaction of time and treatment group and other relevant covariates. There were no statistically significant differences between the two groups in terms of gender, age, body mass index, and insurance type. ACB patients had significantly higher pain scores than IAB patients at hours 1 and 2 (hour 1: 4.02 [2.99] vs. 2.59 [3.00], p = 0.009; hour 2: 3.12 [2.44] vs. 2.17 [2.62], p = 0.040). ACB patients had higher pain scores than IAB patients up to hour 16, though hours 4 to 16 were not significantly different. Adjusted covariate analyses demonstrate an additional statistically significant reduction in pain score in the IAB group at hour 4. There were no differences in narcotic consumption. Intraoperative local anesthetic and regional ACB each provides adequate pain control following knee arthroscopy, and intraoperative local anesthetic may provide enhanced pain control for up to 4 hours postoperatively. LEVEL OF EVIDENCE: : Level 1 evidence, randomized control trial.

Characterization of an oligometastatic state in patients with metastatic pancreatic adenocarcinoma undergoing systemic chemotherapy.

PURPOSE/OBJECTIVES: Most patients with pancreatic adenocarcinoma (PDAC) will present with distant metastatic disease at diagnosis. We sought to identify clinical characteristics associated with prolonged overall survival (OS) in patients presenting with metastatic PDAC. MATERIALS/METHODS: Patients presenting with metastatic PDAC that received treatment at our institution with FOLFIRINOX or gemcitabine-based chemotherapies between August 1, 2011 and September 1, 2017 were included in the study. Metastatic disease burden was comprehensively characterized radiologically via individual diagnostic imaging segmentation. Landmark analysis was performed at 18 months, and survival curves were estimated using the Kaplan-Meier method and compared between groups via the log-rank test. ECOG and Charlson Comorbidity Index (CCI) were calculated for all patients. RESULTS: 121 patients were included with a median age of 62 years (37-86), 40% were female, 25% had ECOG 0 at presentation. Of the 121 patients included, 33% (n = 41) were alive at 12 months and 25% (n = 31) were alive at 18 months. Landmark analysis demonstrated a significant difference between patients surviving <18 months and ≥18 months regarding the presence of lung only metastases (36% vs. 16%, p = 0.04), number of organs with metastases (≥2 vs. 1, p = 0.04), and disease volume (mean of 19.1 cc vs. 1.4 cc, p = 0.04). At Year 1, predictors for improved OS included ECOG status at diagnosis (ECOG 0 vs. ECOG 1, p = 0.04), metastatic disease volume at diagnosis (≤0.1 cc vs. >60 cc, p = 0.004), metastasis only in the liver (p = 0.04), and normalization of CA 19-9 (p < 0.001). At Year 2, the only predictor of improved OS was normalization of the CA 19-9 (p = 0.03). In those patients that normalized their CA 19-9, median overall survival was 16 months. CONCLUSIONS: In this exploratory analysis normalization of CA-19-9 or volumetric metastatic disease burden less than 0.2 cc demonstrated a remarkable OS, similar to that of patients with non-metastatic disease. These metrics are useful for counseling patients and identifying cohorts that may be optimal for trials exploring metastatic and/or local tumor-directed interventions.

Older Patients With Asymptomatic Primary Hyperparathyroidism: Should Criteria for Surgery Be Expanded?

Context: Patients with primary hyperparathyroidism (PHPT) can present with variable signs, symptoms, and end-organ effects. Clinical practice guidelines influence referral for consideration of parathyroidectomy. Objective: This study compared the demographic, biochemical, and symptom profile and examine indications for surgery in patients older than 50 years who underwent parathyroidectomy to determine how changes to current guidelines may affect recommendations for parathyroidectomy. Methods: A retrospective review was conducted of patients age 50 years or older who underwent initial parathyroidectomy for sporadic PHPT from 2012 to 2020. Patients were classified by indications for surgery per guideline criteria (classic, asymptomatic, and no criteria met) and age group (AG): 50 to 59 years; 60 to 69 years; 70 years or older. Patients were treated at a high-volume tertiary medical center by endocrine surgeons. Results: Of 1182 patients, 367 (31%) classic and 660 (56%) asymptomatic patients met the criteria for surgery. The most common indications for surgery were extent of hypercalcemia (51%), osteoporosis (28%), and nephrolithiasis (27%). Of the 155 (13%) patients who did not meet the criteria, neurocognitive symptoms (AG1: 88% vs AG2: 81% vs AG3: 70%; P = .14) and osteopenia (AG1: 53% vs AG2: 68% vs AG3: 68%; P = .43) were frequently observed regardless of patient age. If the age threshold of younger than 50 years was expanded to 60, 65, or 70 years, an additional 61 (5%), 99 (8%), and 124 (10%) patients in the entire cohort would have met the guideline criteria for surgery, respectively. Conclusion: Expanding current guidelines for PHPT to include a broader age range, osteopenia, and neurocognitive symptoms may allow for earlier surgical referral and evaluation for definitive treatment.

Going for Broke: The Impact of Cost of Living on Surgery Resident Stipend Value.

OBJECTIVE: The objective of this study was to provide a direct comparison of first-year general surgery resident stipends across states and major cities, using the Cost-of-Living Index (COLI) to determine stipend value. BACKGROUND: Financial challenges are among residents' top sources of stress, and this may be exacerbated in areas with high costs of living. A 2021 survey found that the mean first-year medical resident stipend increased by 0.6%, or $358, from 2020 to 2021, and only 33% of institutions used cost-of-living to determine annual resident stipend adjustments. METHODS: An American Medical Association database was used to identify accredited general surgery residency programs. The 2021-2022 stipend data for first-year general surgery positions were obtained, then data were grouped by state and major city and averaged. Major cities were defined as cities with >4 programs.A direct comparison of stipends was performed using the COLI. RESULTS: Stipend data were available for 337 of 346 general surgery programs. The national average first-year residency stipend was $60,064±$4233. The average COLI-adjusted stipend was $57,090±$5742, with a value loss of -$3493, or 5%.For major cities, the average stipend was $63,383±$4524, and the average COLI-adjusted stipend was $46,929±$8383, with an average value loss of -$16,454, or 26%. CONCLUSIONS: The financial burdens that residents face cannot be overlooked, and the cost of living has a meaningful impact on resident stipend value. The current Graduate Medical Education compensation structure limits federal and institutional capacity to adjust for the cost of living and creates an insulated market in which residents are under-compensated.

Biliary Adverse Events During Neoadjuvant Therapy for Pancreatic Cancer.

OBJECTIVE: To describe a high-volume experience with biliary drainage before neoadjuvant therapy (NAT) for patients with operable pancreatic cancer (PC) and characterize the association between biliary adverse events (BAEs) and patient outcome. BACKGROUND: Patients with PC presenting with biliary obstruction require durable decompression before NAT. METHODS: Patients with operable PC and tumor-associated biliary obstruction were examined and grouped by the presence or absence of a BAE during NAT. The incidence, timing, and management of BAEs are described, and outcomes, including the completion of all treatment and overall survival (OS), were compared. RESULTS: Of 426 patients who received pretreatment biliary decompression, 92 (22%) experienced at least 1 BAE during NAT, and 56 (13%) required repeat intervention on their biliary stent. The median duration of NAT was 161 days for all patients and was not different in the group that experienced BAEs. The median time from initial stent placement to BAE was 64 days. An interruption in the delivery of NAT (median 7 days) occurred in 25 (6%) of 426 patients. Among 426 patients, 290 (68%) completed all NAT, including surgery: 60 (65%) of 92 patients with BAE and 230 (69%) of 334 patients without BAE ( P =0.51). Among 290 patients who completed NAT and surgery, the median OS was 39 months, 26 months for the 60 patients with BAE, and 43 months for the 230 patients without BAE ( P =0.02). CONCLUSIONS: During extended multimodal NAT for PC, 22% of patients experienced a BAE. Although BAEs were not associated with a significant interruption of treatment, patients who experienced a BAE had worse OS.

Patterns of Unnecessary Insurer Prior Authorization Denials in a Complex Surgical Oncology Practice.

INTRODUCTION: Insurance prior authorization (PA) is a determination of need, required by a health insurer for an ordered test/procedure. If the test/procedure is denied, a peer-to-peer (P2P) discussion between ordering provider and payer is used to appeal the decision. The objective of this study was to measure the number and patterns of unnecessary PA denials. METHODS: This was a retrospective review at a quaternary cancer center from October 2021 to March 2022. Included were all patients with outpatient imaging orders for surgical planning or surveillance of gastrointestinal, endocrine, or skin cancer. Primary outcome was unnecessary initial denial (UID) defined as an order that required preauthorization, was initially denied by the insurer, and subsequently overturned by P2P. RESULTS: Nine hundred fifty seven orders were placed and 419 required PA (44%). Of tests requiring authorization, 55/419 (13.1%) were denied. Variability in the likelihood of initial denial was seen across insurers, ranging from 0% to 57%. Following P2P, 32/55 were overturned (58.2% UID). The insurers most likely to have a UID were Aetna (100%), Anthem (77.8%), and Cigna (50.0%). UID was most common for gastrointestinal (58.9%) and endocrine (58.3%) cancers. Average P2P was 33.5 min (interquartile range 28-40). CONCLUSIONS: The majority of imaging studies initially denied were overturned after P2P. If all UIDs were eliminated, this would represent 108 less P2P discussions with an estimated time-savings of 60.3 h annually within a high-volume surgical oncology practice. Combined personnel costs to the health systems and stress on patients with cancer due to image-associated PAs and P2P appear hard to justify.

Neoadjuvant chemotherapy for pancreatic cancer: Quality over quantity.

BACKGROUND AND OBJECTIVES: The ideal duration of neoadjuvant chemotherapy (NACT) in patients with localized pancreatic adenocarcinoma (PDAC) treated with curative intent is unclear. We sought to determine the prognostic significance of both duration of NACT and Carbohydrate Antigen 19-9 (CA19-9) normalization to NACT. METHODS: We examined patients with resectable and borderline resectable PDAC treated with NACT and chemoradiation. Patients were compared by NACT duration (2 vs. 4 months) and by CA19-9 normalization after NACT. RESULTS: Among 171 patients, 83 (49%) received 2 months of NACT, and 88 (51%) received 4 months. After NACT completion, 115 (67%) patients had persistently elevated CA19-9, and 56 (33%) had normalized. Of the 125 patients who had successful surgery, 73 (58%) had normalized CA19-9 postoperatively. Duration of NACT was not associated with overall survival (OS) while CA19-9 normalization after NACT (regardless of duration) was associated with improved OS (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.35-0.89, p = 0.02). Adjuvant chemotherapy was associated with improved OS among patients without CA19-9 normalization after NACT (HR 0.42, CI 0.20-0.86, p = 0.02) but not among those that normalized, independent of duration. CONCLUSIONS: CA19-9 normalization after NACT is a clinically significant endpoint of treatment; patients without CA19-9 normalization may benefit from additional therapy.

CA19-9 Response to First-Line Neoadjuvant FOLFIRINOX and Second-Line Gemcitabine/Nab-Paclitaxel for Patients with Operable Pancreatic Cancer.

BACKGROUND: Response to second-line (2L) neoadjuvant therapy for operable pancreatic cancer (PC) is understudied. This study examined carbohydrate antigen 19-9 (CA19-9) response to first-line (1L) and 2L chemotherapy. METHODS: The study identified patients with operable PC and elevated CA19-9 (≥ 35 U/mL with total bilirubin < 2 mg/dL) who received 1L FOLFIRINOX (FFX). The patients were restaged after 2 months and based on response, received additional FFX or gemcitabine/nab-paclitaxel (GnP) as part of total neoadjuvant therapy. Response was defined as a decrease in tumor size on computed tomography (CT) imaging or a decline in CA19-9 of 50% or more and preserved performance status. RESULTS: For operable PC with an elevated CA19-9, 108 patients received 1L FFX. After 2 months of chemotherapy, the decision was made to continue FFX (FFX ≥ FFX) for 76 (70%) of the 108 patients and switch to GnP (FFX ≥ GnP)) for 32 (30%) of the patients. Of the 32 FFX ≥ GnP patients, 27 had no evidence of radiographic or biochemical (CA19-9) response to 1L FFX. Of these 27 patients, 26 (96%) demonstrated a response to 2L GnP. After 4 months of chemotherapy, 62 (82%) of the 76 FFX ≥ FFX patients had a CA19-9 response compared with 31 (97%) of the 32 FFX ≥ GnP patients (p = 0.04). CONCLUSIONS: Lack of biochemical response to 2 months of 1L FFX may identify a subgroup of patients with a very high rate of response to 2L GnP, emphasizing the importance of assessing treatment response at 2-month intervals.