BackgroundPatients with gastric cancer and isolated positive peritoneal cytology have stage IV disease. The clinical significance of cytologic conversion is poorly understood. Our objectives are to (1) describe the clinicopathologic characteristics of patients with gastric cancer and isolated positive peritoneal cytology and their association with survival, (2) evaluate patients who underwent second cytologic evaluation for assessment of cytologic conversion, and (3) describe recurrence patterns in patients with cytologic conversion who underwent resection.Patients and MethodsPatients with gastric adenocarcinoma and isolated positive peritoneal cytology were identified from a prospectively maintained institutional database from 1996 to 2020 for this cohort study. Patients were characterized by selection for second cytologic evaluation following chemotherapy, cytologic conversion, and selection for surgical resection. Factors associated with overall survival (OS) were evaluated by time-dependent multivariable Cox regression models.ResultsOverall, 174 patients were identified, 62 (35.6%) were selected for second cytologic evaluation, 43 (69.4%) were cytologic converters, and 32 (74.4, 18.4% overall) underwent resection. Selection for second cytologic evaluation was associated with improved OS (hazard ratio [HR] 0.56, 95% CI 0.37-0.86), and among those patients, cytologic conversion was associated with improved OS (HR 0.17, 95% CI 0.08-0.35). Ten patients (31.3%) had no evidence of recurrence following resection during the study period. The peritoneum was the most common site of recurrence (n = 17, 53.1%).ConclusionsAmong patients with gastric cancer and isolated positive peritoneal cytology, second cytologic evaluation can provide prognostic information and inform treatment decisions. Cytologic conversion was documented in 25% of patients, with rare instances of long-term disease control.

Background: Minimally invasive surgery (MIS) is prevalent in surgical oncology. While some studies suggest that MIS is associated with perioperative benefits and comparable oncologic outcomes, more recent studies in robotic surgery dispute these findings. We aim to assess perioperative and oncologic outcomes with robotic, laparoscopic/ thoracoscopic, and open procedures across multiple surgical oncology specialties. Methods: We performed a retrospective review of all patients >= 18 years of age, at Memorial Sloan Kettering Cancer Center (MSKCC), who underwent robotic, laparoscopic /thoracoscopic, and open procedures between January 2000 and December 2018. Patients with the following disease sites were included: lung, thymus, esophagus, stomach, colon, distal pancreas, renal, prostate, urothelial, cervical, and uterine. Analyses were conducted within each procedure separately. After propensity-score weighting, multivariable models including survey-weighted generalized linear regressions and Cox regressions quantified the association between surgical approach and outcomes. Results: Compared to open surgery, robotic and laparoscopic surgeries were associated with shorter length of stay but longer operative times. Oncologic outcomes, including resection margins and number of nodes harvested, were comparable with MIS across most procedures. Recurrence-free survival and overall survival following MIS were comparable to those observed with other surgical approaches. Conclusion: MIS, including robotic-assisted techniques, are associated with similar perioperative and oncologic outcomes compared to open surgery. Our findings support MIS as a safe and viable option for oncologic procedures.

INTRODUCTION:Merkel cell carcinoma (MCC) is an uncommon neuroendocrine cutaneous malignancy considered to have a high risk of local recurrence (LR). We investigated the true risk of LR in patients with MCC treated by surgical excision alone. PATIENTS AND METHODS:Patients with clinically localized MCC excised with pathologically negative surgical margins were identified from a prospectively maintained single-institution database from November 1980 through December 2022. The cumulative incidence of LR, defined as recurrence within 5 cm of the surgical scar, was estimated using death as a competing event. RESULTS:Among 447 patients, 393 (88%) were treated with surgery alone, and 54 (12%) also received adjuvant radiotherapy (RT) to the primary site. LR occurred in eight patients, with seven recurrences detected within 12 months of treatment. All recurrences occurred in patients treated with surgery alone for a 1-year LR rate of 1.8% (95% confidence interval [CI] 0.8-3.6%). At a median follow-up of 8.8 years (95% CI 7.6-10) from presentation, of the six patients with LR alone, all treated with surgery and/or RT, four patients had no evidence of disease and two died of other causes. Two patients developed distant metastases at the time of LR; both received systemic therapy and died of disease. The low incidence of LR precluded analysis of risk factors. CONCLUSIONS:Negative-margin surgery without adjuvant RT provides excellent local control, with an LR rate of 1.8%. LR was effectively treated with surgery and/or RT. These data do not support the routine use of adjuvant RT for all patients after complete excision of primary MCC.

Tumor location-modified Laurén classification (mLC) of gastric adenocarcinoma (GAC) integrates Laurén histologic subtype and tumor location. mLC has been previously proposed and clinically validated as an independent prognostic indicator. However, the genomic signatures of GAC within the mLC system are unknown, particularly among mixed tumors. This study aimed to characterize the genomic signatures of GAC using the mLC system and to elucidate the genomic patterns of morphologically distinct components of mixed tumors. Treatment-naive GAC tumors were classified according to the mLC into 4 subgroups: proximal-intestinal, distal-intestinal, diffuse, and mixed types. The latter included 2 components: mixed-intestinal and mixed-signet ring. Sections of formalin-fixed, paraffin-embedded tissues were subjected to next-generation targeted sequencing. Tumors from 103 patients were included. The proximal-intestinal (n=28), distal-intestinal (n=34), and diffuse (n=25) subgroups exhibited distinct genomic alteration patterns. Among microsatellite stable cases, the proximal-intestinal subgroup was enriched for alterations in TP53 , ERBB2, CDKN2A , and SMAD4 , whereas the diffuse subgroup had significantly more alterations in CDH1 and ARID1A . The distal-intestinal subgroup had significantly more TP53 alterations than the diffuse subgroup. At the pathway level, both the proximal-intestinal and distal-intestinal subgroups had significantly higher TP53 pathway alterations than the diffuse subgroup. The proximal-intestinal subgroup had a significantly higher percentage of cell cycle, PI3K, and TGF-ß alterations than the diffuse subgroup. Both the mixed-intestinal and mixed-signet ring components of mixed tumors (n=16) exhibited alteration patterns that partially resembled those of the distal-intestinal and diffuse subgroups. The matched components of mixed tumors shared some, but not all, alterations. Overall, this study demonstrated distinct genomic patterns among the proximal-intestinal, distal-intestinal, and diffuse subgroups in the mLC system. The gene alteration patterns in the mixed-intestinal and mixed-signet ring components of mixed tumors exhibited partial similarities with both the distal-intestinal and diffuse subgroups. Furthermore, this study emphasizes how employing a multisampling approach can uncover the molecular heterogeneity of histologically distinct components of mixed-type tumors.

Merkel cell carcinoma (MCC) is a rare, cutaneous malignancy with a propensity for nodal metastasis, for which prognostic factors remain poorly characterized. All patients treated from April 1996 through December 2022 by wide excision and sentinel lymph node (SLN) biopsy for clinically localized MCC at a single institution were included. Logistic regression was used to evaluate factors associated with a positive SLN, recurrence, and disease-specific death (DSD). Cumulative incidence functions estimated recurrence and DSD with death from other causes as a competing risk. Of 342 patients with MCC, 140 (41

BACKGROUND:18F-FDG PET-CT-based host metabolic (PETMet) profiling of non-tumor tissue is a novel approach to incorporate the patient-specific response to cancer into clinical algorithms. MATERIALS AND METHODS:A prospectively maintained institutional database of gastroesophageal cancer patients was queried for pretreatment PET-CTs, demographics, and clinicopathologic variables. 18F-FDG PET avidity was measured in 9 non-tumor tissue types (liver, spleen, 4 muscles, 3 fat locations). Logistic and Cox regression were used to model pathologic response (PR) and overall survival (OS) respectively. Classification and regression tree (CART) and random forest modeling were employed to create decision trees and identify PETMet features associated with outcome. RESULTS:Two-hundred and one patients with distal gastroesophageal (48 %) or gastric (52 %) adenocarcinoma were included. PET-CT-derived scores were independently associated with PR after adjusting for clinical variables. CART and Random Forest methods identified critical split points of non-tumor tissue 18F-FDG avidity that can classify patients and predict PR. PET-CT risk groups created from decision trees predicted PR significantly better than the clinical model (p < 0.001). Specifically, an elevated erector spinae-to-gluteal fat 18F-FDG avidity ratio (≥2.7) combined with low 18F-FDG avidity in the spleen (<2.9) and rectus femoris (<0.52) predict PR. No advantage of PET-CT risk groups was seen for predicting OS (p = 0.155). CONCLUSIONS:Pretreatment host PETMet features may be useful for predicting PR after neoadjuvant therapy in gastroesophageal cancer. Unsupervised decision trees indicate that low 18F-FDG avidity in visceral fat, subcutaneous fat, and muscle result in the most favorable PR, suggesting that systemic hypermetabolism adversely impacts prognosis.

INTRODUCTION:Gastric cancer incidence, risk factors, and survival outcomes differ significantly between Japan and the United States. These disparities have led to the belief that gastric cancer represents biologically distinct diseases across regions. However, direct genomic comparisons of tumours from these populations have not been performed. The aim of this study was to compare the genomic and clinical characteristics of gastric cancers in patients from the US and Japan following curative-intent resection. METHODS:A retrospective cohort study of patients who underwent curative-intent gastrectomy between 2010 and 2019 at Memorial Sloan Kettering (MSK, n = 142) and Fujita Health University (FHU, n = 108), with ≥5 years of follow-up, was conducted. Tumour samples underwent targeted sequencing. Clinical and genomic data were compared between unmatched and propensity score-matched (PSM) cohorts, matched by age, sex, clinical T/N-category, and tumour location (n = 58 each). RESULTS:Commonly altered genes included TP53 (60%), ARID1A (17%), ERBB2 (14%), CCNE1 (13%), and KRAS (12%). MSK tumours showed higher rates of microsatellite instability (MSI-high; 22.4% versus 5.2%, P = 0.013) and KMT2D mutations (18% versus 5%, P < 0.05). Otherwise, gene- and pathway-level alterations were similar across unmatched, microsatellite stable only, and PSM cohorts. Five-year overall survival in PSM cohorts was comparable (MSK 60% versus FHU 69.4%, P = 0.548). Peritoneal recurrence was more common in the MSK cohort (47% versus 34%), but recurrence patterns were not associated with distinct genomic profiles. CONCLUSION:After adjustment for clinical covariates, US and Japanese gastric cancers exhibit comparable genomic landscapes and survival, supporting the relevance of clinical trial data across geographic settings.

OBJECTIVE:High-risk oncologic resections are the primary curative interventions for solid upper gastrointestinal (GI) tumors; however, there are no cancer-specific risk-stratification models available for these operations. METHODS:We studied 2823 Memorial Sloan Kettering Cancer Center patients (2015-2022) undergoing upper GI oncologic resections including gastrectomy, esophagectomy, distal pancreatectomy, and pancreaticoduodenectomy for adenocarcinoma. Univariable analyses assessed risk factors for length of stay (LOS) and complications, with multivariable analyses incorporating covariates significant on univariable analysis and procedure type. Nomograms were built using multivariable models to predict surgical complications and LOS. Model performance was evaluated using discrimination (C-index for complications, Kendall's Tau for LOS) and calibration plots and was internally validated with 1000 bootstrap replicates to obtain average performance metrics and 95% confidence intervals. RESULTS:The median LOS was 7.0 (IQR:6.0,10.0), and the overall 30-day postoperative complication rates were 31%. Multivariable analysis identified age, ASA>3, COPD, renal failure, and operation length as independent risk factors for increased LOS (OR>1, P<0.05). Neoadjuvant chemotherapy (NAC) and pre-incision antibiotics reduced LOS (OR<1, P<0.05). The complication nomogram demonstrated a C-index of 0.66, while the LOS nomogram showed a Kendall's Tau of 0.39. Procedure type, age, and history of COPD and NAC had the greatest discriminatory values for LOS on the nomograms; procedure type, race, and BMI had the greatest impact on 30-day surgical complications. CONCLUSION:Our cancer-specific pre- and postoperative nomograms for LOS and postoperative complications provide an important tool to appropriately estimate risks and treatment outcomes for patients undergoing high-risk GI oncologic resections.

PURPOSE:The Cancer Genome Atlas (TCGA) project defined four distinct molecular subtypes of esophagogastric adenocarcinoma: microsatellite instable (MSI), Epstein-Barr virus (EBV)-associated, genomically stable (GS), and chromosomally instable (CIN). However, an association between molecular subtypes and clinical outcomes has not been clearly demonstrated. Given few actionable biomarkers, we investigated the clinical relevance of TCGA classification system. EXPERIMENTAL DESIGN:We identified all patients with esophagogastric adenocarcinoma whose tumors underwent prospective next-generation sequencing using the Memorial Sloan Kettering-IMPACT assay from 2014 to 2023. We classified all tumors in accordance with TCGA methodology and correlated molecular subtypes with high-quality clinicopathologic data. RESULTS:Among 1,438 included patients, 941 had CIN, 344 had GS, 103 had MSI, and 50 had EBV tumors. Accounting for the clinical stage and tumor grade, molecular classification was independently associated with overall cancer-specific survival (P < 0.001) on Cox multivariable analysis. Furthermore, genomic signatures, patient demographics, pathologic responses to neoadjuvant therapy, patterns of recurrence, and metastatic organotropism differed significantly by molecular subtype. Although most distal esophageal and gastroesophageal junction tumors were CIN, up to 25% of these included GS, MSI, or EBV subtypes in contrast to TCGA. Random forest machine learning demonstrated that the molecular subtype is more influential in predicting response to treatment than tumor location. CONCLUSIONS:Molecular classification is independently prognostic and may warrant inclusion in future staging and treatment guidelines. Routine molecular profiling is clinically feasible and may play a role in the management of patients to help guide appropriate treatment selection and clinical trial enrollment in the place of tumor location.

250 Background: While the rate of esophagogastric (EG) cancer is declining, early onset (EO) gastric cancer prior to age 50 is rising. It is unknown whether EO-EG cancer represents a distinct entity. This study investigates the clinical and molecular characteristics of EO compared with average onset (AO)-EG cancers. Methods: We reviewed clinical and molecular features of gastric (G), esophageal (E) and gastroesophageal junction (GEJ) cancer in patients treated at MSKCC between 2005 and 2018. We defined early onset as age < 49, based on the age cutoff for urgent endoscopy referral. Clinical symptoms at diagnosis, primary tumor location, histology, HER2 and MSI status and molecular alterations were compared using Fisher’s exact test. Benjamini-Hochberg method was used to decrease the false discovery rate. Results: We analyzed 738 pts with EG cancer (age < 49 n=151; age >50 n=587). Race and sex were different with more Asian (19% vs. 9%), fewer Caucasian (62% vs. 81%) ( P<0.001) and more female patients (40% vs. 29%, P=0.014) in the EO group. Time from symptom onset to diagnosis was longer in the EO group (median (IQR) 144 d (66-276) vs. 75 d (34-136), P=0.009), though stage did not differ ( P=0.49). Patients with EO-EG cancer had less weight loss ( P<0.001), but no other distinct presenting symptoms. Primary disease site was different with more gastric in the EO group (66% vs. 55%, P=0.04). Signet-ring histology was more common in the EO group (11% vs. 3%; P=0.0009). ERBB2 amp and MSI-H were similar, with a trend toward more MSI-H in the AO group (ERBB2 amp P=0.88, Q=0.830; MSI-H P=0.0157, Q=0.056). The most frequent somatic alterations were similar in EO vs. AO pts, including TP53 (68% vs. 70%, P=0.370, Q=0.825), CDH1 (15% vs. 11%, P=0.139, Q=0.825), RHOA (6% vs. 5%, P=0.395, Q=0.825). There was a trend toward more ARID1A (19% vs. 7%, P<0.01, Q=0.250) and FBWX7 (5% vs. 2%, P=139, Q=0.825) mutations in the AO group. Conclusions: Presenting symptoms, stage, histology, HER2 and MSI status are similar in patients with EO vs. AO-EG cancer. There is a trend in EO toward longer time to diagnosis, gastric primary site of disease, signet-ring histology and fewer ARID1A and FBWX7 mutations. Expanded clinical and molecular data will be presented. [Table: see text]

Importance Patients with melanoma are selected for sentinel lymph node biopsy (SLNB) based on their risk of a positive SLN. To improve selection, the Memorial Sloan Kettering Cancer Center (MSKCC) and Melanoma Institute Australia (MIA) developed predictive models, but the utility of these models remains to be tested.Objective To determine the clinical utility of the MIA and MSKCC models.Design, Setting, and Participants This was a population-based comparative effectiveness research study including 10 089 consecutive patients with cutaneous melanoma undergoing SLNB from the Swedish Melanoma Registry from January 2007 to December 2021. Data were analyzed from May to August 2023.Main Outcomes and Measures, The predicted probability of SLN positivity was calculated using the MSKCC model and a limited MIA model (using mitotic rate as absent/present instead of count/mm(2) and excluding the optional variable lymphovascular invasion) for each patient. The operating characteristics of the models were assessed and compared. The clinical utility of each model was assessed using decision curve analysis and compared with a strategy of performing SLNB on all patients.Results Among 10 089 included patients, the median (IQR) age was 64.0 (52.0-73.0) years, and 5340 (52.9%) were male. The median Breslow thickness was 1.8 mm, and 1802 patients (17.9%) had a positive SLN. Both models were well calibrated across the full range of predicted probabilities and had similar external area under the receiver operating characteristic curves (AUC; MSKCC: 70.8%; 95% CI, 69.5-72.1 and limited MIA: 69.7%; 95% CI, 68.4-71.1). At a risk threshold of 5%, decision curve analysis indicated no added net benefit for either model compared to performing SLNB for all patients. At risk thresholds of 10% or higher, both models added net benefit compared to SLNB for all patients. The greatest benefit was observed in patients with T2 melanomas using a threshold of 10%; in that setting, the use of the nomograms led to a net reduction of 8 avoidable SLNBs per 100 patients for the MSKCC nomogram and 7 per 100 patients for the limited MIA nomogram compared to a strategy of SLNB for all.Conclusions and Relevance This study confirmed the statistical performance of both the MSKCC and limited MIA models in a large, nationally representative data set. However, decision curve analysis demonstrated that using the models only improved selection for SLNB compared to biopsy in all patients when a risk threshold of at least 7% was used, with the greatest benefit seen for T2 melanomas at a threshold of 10%. Care should be taken when using these nomograms to guide selection for SLNB at the lowest thresholds.

ABSTRACTBackgroundThere has been a paradoxical rise in young‐onset gastric cancer (YOGC), defined as gastric cancer (GC) diagnosed before age 50. Precursor lesions may contribute to pathogenesis, though their role in progression to different histologic subtypes is unclear. The impact of self‐reported race is also poorly characterized and may be unreliable as a proxy for genetic differences. We aimed to compare differences in histology and genetic ancestry between YOGC and average‐onset gastric cancer (AOGC).MethodsThis retrospective cohort included all patients with GC at Memorial Sloan Kettering (MSK) from January 2013 to March 2021. Data on demographics, tumor characteristics, and precursor lesions were collected. Genetic ancestry was inferred from MSK‐Integrated Mutation Profiling of Actionable Cancer Targets panel.ResultsOf 1685 individuals with GC, 290 had YOGC. Compared to AOGC, individuals with YOGC tended to be female, Hispanic, foreign‐born, and feature diffuse‐type histology. YOGC was less likely to have precursor lesions, including intestinal metaplasia (20% vs. 37%, p < 0.01) and dysplasia (4% vs. 14%, p < 0.01). Of 560 patients with ancestry data, 127 had YOGC. Admixed, East Asian, and South Asian ancestries were more likely to present with YOGC while Europeans presented with AOGC. Intestinal metaplasia was enriched among East Asians, maintained when stratifying by histology and GC onset.ConclusionsWe observed YOGC was more common in East and South Asians, and while YOGC may be less likely to develop in the setting of precursor lesions these high‐risk states may also be enriched in East Asians. Future research is needed to understand drivers behind such differences and outcome disparities given these individuals may be less amenable to endoscopic interventions.

BACKGROUND: For patients with melanoma, the decision to perform sentinel lymph node biopsy (SLNB) is based on the estimated risk of lymph node metastasis. We assessed 3 melanoma SLNB risk-prediction models’ statistical performance and their ability to improve clinical decision making (clinical utility) on a cohort of melanoma SLNB cases. STUDY DESIGN: Melanoma patients undergoing SLNB at a single center from 2003 to 2021 were identified. The predicted probabilities of sentinel lymph node positivity using the Melanoma Institute of Australia, Memorial Sloan Kettering Cancer Center (MSK), and Friedman nomograms were calculated. Receiver operating characteristic and calibration curves were generated. Clinical utility was assessed via decision curve analysis, calculating the net SLNBs that could have been avoided had a given model guided selection at different risk thresholds. RESULTS: Of 2,464 melanoma cases that underwent SLNB, 567 (23.0%) had a positive sentinel lymph node. The areas under the receiver operating characteristic curves for the Melanoma Institute of Australia, MSK, and Friedman models were 0.726 (95% CI, 0.702 to 0.750), 0.720 (95% CI, 0.697 to 0.744), and 0.721 (95% CI, 0.699 to 0.744), respectively. For all models, calibration was best at predicted positivity rates below 30%. The MSK model underpredicted risk. At a 10% risk threshold, only the Friedman model would correctly avoid a net of 6.2 SLNBs per 100 patients. The other models did not reduce net avoidable SLNBs at risk thresholds of ≤10%. CONCLUSIONS: The tested nomograms had comparable performance in our cohort. The only model that achieved clinical utility at risk thresholds of ≤10% was the Friedman model.

Summary: Patients undergoing extensive lymph node dissection and radiation are at high risk for not only lymphedema but also painful contracture. In a standard lymphadenectomy, immediate lymphatic reconstruction using a lymphovenous bypass is effective in reconstructing the lymphatic defect. However, a more aggressive nodal clearance leaves the patient with a large cavity and skeletonized neurovascular structures, often resulting in severe contracture, pain, cosmetic deformity, and venous stricture. Adjuvant radiotherapy to the nodal bed can lead to severe and permanent disability despite physical therapy. Typically, these patients are referred to us after the fact, where surgery will rarely restore the patient to normal function. In an effort to avoid lymphedema and contracture, we have been reconstructing both the lymphatic and soft tissue defect during lymphadenectomy, using vascularized omentum lymphatic transplant (VOLT). A total of 13 patients underwent immediate reconstruction with VOLT at the time of axillary (n = 8; 61.5%) or groin (n = 5; 38.5%) dissection. No postoperative complications were observed. The mean follow-up time was 15.1 ± 12.5 months. Only one lower extremity patient developed mild lymphedema (11% volume differential), with excellent scores in validated patient-reported outcomes. All patients maintained full range of motion with no pain. None of the 13 patients required a compression garment. Immediate lymphatic reconstruction with VOLT is a promising procedure for minimizing the risk of lymphedema and contracture in the highest risk patients undergoing particularly extensive lymph node dissection and radiotherapy.

Clinicopathologic data-based sentinel lymph node (SLN) prediction models are used to select patients with melanoma for sentinel lymph node biopsy (SLNB). However, the temporal performance of these models is unknown. Therefore, we investigated whether the performance and clinical utility of the Melanoma Institute of Australia, Memorial Sloan Kettering Cancer Center, and Friedman et al. models changed over time. Primary cutaneous melanoma cases that underwent SLNB at a single tertiary-care cancer center from 2000 to 2021 were identified from a prospectively maintained database. Calibration plots were generated. Values for estimated risks of SLN positivity and area under the receiver operator curve (AUC) were calculated. Clinical utility was assessed at thresholds between 5 and 10