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Background: Current management for triple negative breast cancer (TNBC) involves chemotherapy and immunotherapy systemic treatments. TNBC treatment remains a challenge, with up to 40% of those treated using standard methods for stage I to III TNBC experiencing recurrence. Currently, the optimal carboplatin regimen for TNBC is yet to be defined. In our previous study, we identified an optimal carboplatin containing chemotherapy regimen that improved patient outcomes. In this study, we expanded the cohort as an extension of the previous prospective study to further verify these promising results. Patients and Methods: We performed a retrospective review of 37 TNBC patients who had < 10% estrogen and progesterone receptor positivity and were human epidermal growth factor receptor-2 (HER2) negative. This study was originally done in an adjuvant setting, but patients with locally advanced tumors received neoadjuvant chemotherapy. Patients received dose-dense Adriamycin, cyclophosphamide, and paclitaxel every two weeks for sixteen weeks. Adriamycin (60 mg/m^2) and cyclophosphamide (600 mg/m^2) were given intravenously every two weeks for four cycles, followed by paclitaxel (175 mg/m^2) every two weeks for four cycles. Carboplatin with an area under the curve of 6 was added to cycles two and four of paclitaxel. Last, we changed the parameters of continuing chemotherapy to allow platelet counts > 70,000 × 10^9. Only paclitaxel could be modified for neuropathy. Results: Of 37 patients enrolled in this trial, 35 patients survived without recurrence, one required a dose reduction in paclitaxel, and one has incomplete staging as grade is still pending. The two patients that did experience recurrence died. Of these two patients, the first had American Joint Committee on Cancer (AJCC) 7 stage IIIC cancer, and the second had two separate TNBCs at presentation – AJCC-7 IIB cancer of the right breast and AJCC-7 IIA cancer of the left breast. Under the AJCC-8 system, the first patient had AJCC-8 IIIB cancer, while the second patient had AJCC-8 IIIB cancer of the right and left breasts. These data suggest a completion rate of 97%, overall survival (OS) rates of 95% (AJCC-7 & 8), and progression free survival (PFS) rates of 95% and 94% (AJCC-7 & 8, respectively; Table 1). Additional stage-specific survival metrics and patient staging information are available in Table 1. Median follow-up in this study was 3.14 years. This is consistent with data from our previous study with significant PFS benefit over historic chemotherapy. All patients completed this regimen with no dose reductions of carboplatin and a 32% dose reduction in paclitaxel due to neuropathy. Toxicity was established in our previous study. The favourable toxicity profiling of the regimen allowed maximal tolerance for patients. Conclusion: Although administration of carboplatin with chemotherapy for TNBC is known to be beneficial, the ideal carboplatin containing regimen has not been identified because of concerns regarding toxicity and low completion rates. Here, an optimal carboplatin-containing regimen identified in our previous clinical trial led to 95% overall survival rates (AJCC-7 & 8), 95% and 94% progression free survival rates (AJCC-7 & 8, respectively), and a 97% completion rate for 37 TNBC patients. A limitation is that this is a small single center trial, and plans are underway to test this regimen with immunotherapy in a larger randomized control trial. Table 1: Patient Staging and Survival Metrics. Citation Format: Geoffrey J. Rempel, Claire S. Rim, Abdulkadir Hussein, Alina Bocicariu, Swati Kulkarni, Rasna Gupta, John Matthews, Amin Kay, Lisa Porter, Caroline Hamm. Identification of Optimal Carboplatin Containing Regimen for Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-60.

The recent publication of 5-year survival data for the Italian Gastric Cancer Study Group (IGCSG) D1 versus D2 lymphadenectomy for gastric cancer trial adds important data for analysis of whether a D2 lymphadenectomy improves survival. Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1985 to February 1, 2014. Meta-analyses were performed using RevMan version 5 software. Long-term outcomes were analyzed. Subgroup analyses of T and N stage were performed. Outcomes of four randomized, controlled trials involving 1,599 patients (823 D1: 776 D2) enrolled from 1982 to 2005 were included for qualitative analysis and quantitative meta-analysis. Despite the addition of long-term survival data from the IGCSG, 5-year overall and nodal status survival was similar between D1 and D2 trials. However, subgroup analysis revealed a survival benefit for T3 patients (odds ratio 1.64, 95 % confidence interval 1.01–2.67) and a trend for survival benefit for advanced nodal stage (odds ratio 1.36, 95 % confidence interval 0.98–1.87) with D2 compared with D1 lymphadenectomy. As recent studies have demonstrated comparable short-term surgical outcomes for both D1 and D2 lymphadenectomies, consideration should be made for more extensive lymph node dissection among patients with advanced stage.

Nodal status is one of the most important prognostic factors in gastric adenocarcinoma (GC). As such, it is important to assess an appropriate number of lymph nodes (LNs) in order to accurately stage patients. However, the number of LNs assessed in each GC case varies, and in many cases the number examined per gastric specimen is less than current recommendations. We aimed to identify and synthesize findings from all articles evaluating the association of clinicopathological features and long-term outcomes with the number of LNs assessed among GC patients. Systematic electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1998 to 2009. Twenty-five articles were included in this review. Extensive resection, increased tumor size, and greater TNM staging were all associated with a greater number of LNs assessed. The disease-free survival was longer and recurrence rate was lower in patients with more LNs assessed. Overall survival, as well as survival by TNM and clinical stage, was improved among patients with an increased number of LNs assessed, but much of this appears to be due to stage migration, with the effect more pronounced in more advanced disease. More LNs assessed resulted in less stage migration and possibly better long-term outcomes. Although current guidelines suggest 16 LNs to be assessed, especially in advanced GC, a higher number of LNs should be assessed.

In gastric cancer, the utility of sentinel lymph node (SLN) biopsy has not been established. SLN may be a good predictor of the pathological status of other lymph nodes and thus the necessity for more extensive surgery or lymph node dissection. We aimed to identify and synthesize findings on the performance of SLN biopsies in gastric cancer.Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from 1998 to 2009. Titles and abstracts were independently rated for relevance by a minimum of two reviewers. Techniques, detection rates, accuracy, sensitivity, specificity, and false-negative rates (FNRs) were analyzed. Analysis was performed based on the FNR.Twenty-six articles met our inclusion criteria. SLN detection using the dye method (DM) was reviewed in 18 studies, the radiocolloid method (RM) was used in 12 studies, and both dye and radiocolloid methods (DUAL) were used in 5 studies. The DM had an overall calculated FNR of 34.7% (95% confidence interval [CI] 21.2, 48.1). The RM had an overall calculated FNR of 18.5% (95% CI 9.1, 28.0). DUAL had an overall calculated FNR of 13.1% (95% CI -0.9, 27.2).Application of the SLN technique may be practical for early gastric cancer. The use of DUAL for identifying SLN may yield a lower FNR than either method alone, although statistical significance was not met.

Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome specifically associated with germline mutations to the E-cadherin (CDH1) gene. HDGC is characterized by autosomal dominance and high penetrance and a high cumulative risk for advanced gastric cancer. Our purpose in this study was to identify and synthesize findings from all articles on: (1) current recommendations for CDH1 screening and prophylactic gastrectomy; (2) CDH1 testing results in HDGC patients; and (3) prophylactic gastrectomy results in HDGC patients. Systematic electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1985 to 2009. Seventy articles were included in this review. Among patients with a positive family history of gastric cancer, 1085 were screened from 454 families, and 38.4% tested positive. Mutation-positive families also had a considerable family history of breast and colon cancer. Of the 322 patients screened for CDH1 mutations by current HDGC screening criteria, 29.2% tested positive. Among the 76.8% of patients who underwent prophylactic gastrectomy following positive CDH1 test results, 87.0% had positive final histopathology results and 64.6% had signet ring cells identified. Some of the patients with negative final histopathology results had opted to undergo prophylactic gastrectomy prior to CDH1 testing, and were ultimately found to be negative for CDH1 mutations. CDH1 mutation testing in families with a history of gastric cancer and prophylactic gastrectomy in mutation-positive patients are recommended for the management of HDGC.

Surgery is the only curative treatment for patients with gastric cancer. However, the extent of lymph node dissection is still debated. Therefore, with the publication of newer trial results, we conducted an updated meta-analysis of D1 versus D2 randomized controlled trials comparing outcomes. Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1985, to December 31, 2010. Meta-analyses were performed using RevMan v5 software. Both short- and long-term outcomes were analyzed. Subgroup analyses of T stage and spleen/pancreas resection versus preservation were performed. Outcomes of 5 randomized trials involving 1642 patients (845 D1, 797 D2) enrolled from 1982 to 2005 were included. Despite the addition of the more recent trials, overall hospital mortality and reoperation rates were still higher in D2 cases. Subgroup analysis of recent trials and spleen/pancreas preservation revealed no significant difference in hospital mortality between groups. Five-year overall survival was similar between D1 versus D2 trials. Sub-analysis by tumor depth and spleen/pancreas preservation detected trends for improved survival with D2 lymphadenectomy in T3/T4 patients and those with spleen/pancreas preservation. Earlier trials show that D2 dissections have higher operative mortality, while recent trials have similar rates. A trend of improved survival exists among D2 patients who did not undergo resection of the spleen or pancreas, as well as for patients with T3/T4 cancers.

IMPORTANCE There is growing interest in reducing the variations and deficiencies in the multidisciplinary management of gastric cancer. OBJECTIVE To define optimal treatment strategies for gastric adenocarcinoma (GC). DESIGN, SETTING, AND PARTICIPANTS RAND/UCLA Appropriateness Method involving a multidisciplinary expert panel of 16 physicians from 6 countries. INTERVENTIONS Gastrectomy, perioperative chemotherapy, adjuvant chemoradiation, surveillance endoscopy, and best supportive care. MAIN OUTCOMES AND MEASURES Panelists scored 416 scenarios regarding treatment scenarios for appropriateness from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores from 1 to 3 were considered inappropriate; 4 to 6, uncertain; and 7 to 9, appropriate. Agreement was reached when 12 of 16 panelists scored the scenario similarly. Appropriate scenarios agreed on were subsequently scored for necessity. RESULTS For patients with T1N0 disease, surgery alone was considered appropriate, while there was no agreement over surgery alone for patients T2N0 disease. Perioperative chemotherapy was appropriate for patients who had T1-2N2-3 or T3-4 GC without major symptoms. Adjuvant chemoradiotherapy was classified as appropriate for T1-2N1-3 or T3-4 proximal GC and necessary for T1-2N2-3 or T3-4 distal GC. There was no agreement regarding surveillance imaging and endoscopy following gastrectomy. Surveillance endoscopy was deemed to be appropriate after endoscopic resection. For patients with metastatic GC, surgical resection was considered inappropriate for those with no major symptoms, unless the disease was limited to positive cytology alone, in which case there was disagreement. CONCLUSIONS AND RELEVANCE Patients with GC being treated with curative intent should be considered for multimodal treatment. For patients with incurable disease, surgical interventions should be considered only for the management of major bleeding or obstruction.

Hereditary diffuse gastric cancer (HDGC) represents a minority of gastric cancer (GC) cases. The goal of this study is to use a RAND/University of California Los Angeles (UCLA) appropriateness methodology to examine indications for genetic referral, CDH1 testing, and consideration of prophylactic total gastrectomy (PTG).A multidisciplinary expert panel of 16 physicians from six countries scored 47 scenarios. Appropriateness of scenarios was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores (AS) of 1-3 were considered inappropriate, 4-6 uncertain, and 7-9 appropriate. Agreement was reached when 12 of 16 panelists scored the statement similarly. Appropriate scenarios agreed upon were subsequently scored for necessity.The panel felt that patients with family history of diffuse gastric cancer (DGC), lobular breast cancer, or multiple family members with GC should be referred for genetic assessment and multidisciplinary decision-making. The panel felt that it is appropriate for patients with DGC to have CDH1 mutation testing in a family with (1) ≥2 cases of GC, with at least one case of DGC diagnosed before age of 50 years; (2) ≥3 cases of GC diagnosed at any age, one or more of which is DGC; (3) a patient diagnosed with DGC and lobular breast carcinoma; or (4) patients diagnosed with DGC under age of 35 years. The panel felt that PTG should be offered to CDH1 mutation carriers 20 years or older.Identification of genetic mutations in patients at risk for hereditary GC is important, and criteria for testing are suggested.

Savtaj Brar, MD, MSc, Calvin Law, MD, MPH, Robin McLeod, MD, FACS, Lucy Helyer, MD, MSc, Carol Swallow, MD, PhD, FACS, Lawrence Paszat, MD, MSc, Rajini Seevaratnam, MSc, Roberta Cardoso, RN, PhD, Matthew Dixon, MD, Alyson Mahar, MSc, Laercio G Lourenco, MD, Lavanya Yohanathan, MD, Alina Bocicariu, MD, Tanios Bekaii-Saab, MD, Ian Chau, MD, Neal Church, MD, Daniel Coit, MD, FACS, Christopher H Crane, MD, Craig Earle, MD, MSc, Paul Mansfield, MD, FACS, Norman Marcon, MD, Thomas Miner, MD, FACS, Sung Hoon Noh, MD, Geoff Porter, MD, MSc, FACS, Mitchell C Posner, MD, FACS, Vivek Prachand, MD, FACS, Takeshi Sano, MD, PhD, Cornelis van de Velde, MD, PhD, FACS, Sandra Wong, MD, FACS, Natalie Coburn, MD, MPH, FACS

70 Background: Most gastric cancer patients present with advanced stage disease precluding curative surgical treatment. The utility of surgical and non-surgical options for non-curative, advanced disease is debated and the appropriate treatment strategy unclear. Methods: A multi-disciplinary expert panel of 16 physicians from 6 countries, scored 47 scenarios using the RAND/UCLA Appropriateness Methodology. Appropriateness was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores (AS) from 1-3 were considered inappropriate, 4-6 uncertain, and 7-9, appropriate. Agreement was reached when 11 of 16 panelists scored the statement similarly. If a statement was agreed to be appropriate, it was then given a necessity score (NS) in the same manner. Results: Surgical resection and bypass were agreed to be inappropriate in patients with minor symptoms and visible carcinomatosis, liver metastases or more than one site of metastatic disease for cardia and distal lesions (AS 1.0-3.5). The expert panel disagreed on the role for surgical resection in patients who were cytology positive only (AS 4-6). The role of resection for patients with major symptoms if they had visible carcinomatosis, liver metastases or more than one site of metastatic disease (AS 2-5) was indeterminate. Patients with distal tumours and major symptoms and multiple liver metastases or more than one site of metastatic disease were considered indeterminate for surgical resection (AS 2). Best supportive care was agreed to be appropriate for patients with minor symptoms and multiple liver metastases or more than one site of metastatic disease (AS 8, NS 5-6). Conclusions: The role of surgery in metastatic gastric cancer treatment decision-making is not supported by experts for the majority of scenarios. Continued uncertainty in appropriate and necessary treatment decision-making for advanced patients with a minimal burden metastatic disease exists and underscores the need for randomized controlled trials.

104 Background: Processes of care in curative therapy for gastric cancer are ill-defined, have significant variations and may impact patient outcomes. Methods: A multi-disciplinary expert panel (16 physicians, 6 countries) scored 595 scenarios using the RAND/UCLA Appropriateness Methodology. Appropriateness was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores from 1-3 were considered inappropriate, 4-6 uncertain, and 7-9 appropriate. Agreement was reached when 11 of 16 panelists scored the statement similarly. If a statement was agreed to be appropriate, it was given a necessity score in the same manner. Results: Open gastrectomy was considered appropriate for all patients and necessary for patients with N2-3 disease, while laparoscopic gastrectomy was appropriate for patients with T1-2 N0 disease. D1 lymph node dissection (LND) was considered appropriate for T1 N0 disease. For all others, D2 LND was considered appropriate and necessary. It was appropriate to assess at least 15 LN. Intraoperative pathologic assessment of the proximal margin was considered appropriate for gross margins Conclusions: The above criteria have been found to be appropriate and necessary for the curative treatment of patients with gastric cancer and may be used to improve processes and quality of care.