Repeat Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Recurrent Mucinous Appendiceal Adenocarcinoma: A Viable Treatment Strategy with Demonstrable Benefit.

INTRODUCTION: Many patients with mucinous appendiceal adenocarcinoma experience peritoneal recurrence despite complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prior work has demonstrated that repeat CRS/HIPEC can prolong survival in select patients. We sought to validate these findings using outcomes from a high-volume center. PATIENTS AND METHODS: Patients with mucinous appendiceal adenocarcinoma who underwent CRS/HIPEC at MD Anderson Cancer Center between 2004 and 2021 were stratified by whether they underwent CRS/HIPEC for recurrent disease or as part of initial treatment. Only patients who underwent complete CRS/HIPEC were included. Initial and recurrent groups were compared. RESULTS: Of 437 CRS/HIPECs performed for mucinous appendiceal adenocarcinoma, 50 (11.4%) were for recurrent disease. Patients who underwent CRS/HIPEC for recurrent disease were more often treated with an oxaliplatin or cisplatin perfusion (35%/44% recurrent vs. 4%/1% initial, p < 0.001), had a longer operative time (median 629 min recurrent vs. 511 min initial, p = 0.002), and had a lower median length of stay (10 days repeat vs. 13 days initial, p < 0.001). Thirty-day complication and 90-day mortality rates did not differ between groups. Both cohorts enjoyed comparable recurrence free survival (p = 0.82). Compared with patients with recurrence treated with systemic chemotherapy alone, this select cohort of patients undergoing repeat CRS/HIPEC enjoyed better overall survival (p < 0.001). CONCLUSIONS: In appropriately selected patients with recurrent appendiceal mucinous adenocarcinoma, CRS/HIPEC can provide survival benefit equivalent to primary CRS/HIPEC and that may be superior to that conferred by systemic therapy alone in select patients. These patients should receive care at a high-volume center in the context of a multidisciplinary team.

Localized Gastroesophageal Adenocarcinoma in the Elderly: Is Age a Factor Associated with Suboptimal Treatment?

INTRODUCTION: Gastroesophageal adenocarcinoma is relatively common in elderly patients as the incidence increases with age. However, the optimal treatment approach is not well established in this group of patients. The aim of this study is to review our experience for localized gastroesophageal adenocarcinoma in patients aged ≥80 years and to assess association between patient characteristics, clinical factors, and overall survival (OS) in order to optimize the therapeutic approaches for this population. METHODS: Patients ≥80 years old treated for localized gastroesophageal adenocarcinoma were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression models were applied to assess the association between patient characteristics and OS. Factors that were significant in the multivariate model were included in the final reduced model. RESULTS: 127 patients ≥80 years old, were included in this study with median age of 83 years. The median follow-up time was 3.2 years, and median OS was 2.5 years (95% CI: 2.0-3.1 years). Independent prognostic factors for OS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) (p = 0.003), baseline clinical stage (p = 0.01), and surgery (p = 0.001). ECOG PS, tumor location, baseline stage, tumor grade, and surgery were included in the final reduced model. CONCLUSION: Surgical treatment can improve survival in elderly patients. Therapeutic decisions should be based on the patients' general condition rather that age alone.

Cancer of Unknown Primary Presenting as Bone-Predominant or Lymph Node-Only Disease: A Clinicopathologic Portrait.

BACKGROUND: Cancer of unknown primary (CUP) presenting as bone-predominant (BCUP) or lymph node-only disease (LNCUP) represents two clinically distinct subsets of nonvisceral CUP. These present a diagnostic challenge with a large differential of putative primary cancers and defy the "one-treatment-fits-all" approach. MATERIALS AND METHODS: We identified patients with BCUP (n = 29) and LNCUP (n = 63) using a prospectively collected CUP database and tumor registry of patients seen at MD Anderson Cancer Center between 2001 to 2017. Clinicopathological characteristics, treatments, and outcomes were abstracted. A control group of non-BCUP/LNCUP cases (n = 443) from the database was used for comparison. Kaplan-Meier method was used to estimate overall survival and compared using log-rank test. RESULTS: In this cohort, 64% and 60% patients had disseminated disease at diagnosis and 39% and 23% had Culine poor-risk disease in BCUP and LNCUP, respectively. Median overall survival (OS) for BCUP was 14.5 months and for LNCUP was 32.6 months. For BCUP, gemcitabine plus platinum was the most common initial chemotherapy (54%). For LNCUP, carboplatin plus paclitaxel was the most common initial chemotherapy (38%). Radiation was given to 74% of patients with BCUP and 37% of those with LNCUP. On multivariate analysis, poor-risk Culine group (hazard ratio [HR], 1.76; p < .001) and high neutrophil-to-lymphocyte ratio (HR, 2.38, p < .001) were associated with worse OS. CONCLUSION: BCUP and LNCUP are rare subsets within CUP with varying prognosis. Poor-risk Culine group and high neutrophil-to-lymphocyte ratio are associated with poor survival. Select patients with limited metastases can have long-term survival with aggressive multimodality treatment. Careful clinicopathological review can facilitate chances of site-directed therapy. IMPLICATIONS FOR PRACTICE: Cancer of unknown primary (CUP) rarely presents as bone-predominant (BCUP) or lymph node-only (LNCUP) disease. This article describes a cohort of each and compares with a larger CUP cohort. Patients with BCUP have unique issues with fractures and pain, often receiving radiation. Overall survival of 14.5 months was similar to a larger CUP comparison cohort. Patients with LNCUP had improved overall survival at 32.6 months, with longer survival in patients without disseminated disease. Culine poor-risk group and neutrophil-to-lymphocyte ratio were associated with worse overall survival. Tips regarding diagnosis and management of these rare malignant subsets are provided.

Integrated clinico-molecular profiling of appendiceal adenocarcinoma reveals a unique grade-driven entity distinct from colorectal cancer.

BACKGROUND: Appendiceal adenocarcinoma (AA) is an orphan disease with unique clinical attributes but often treated as colorectal cancer (CRC). Understanding key molecular differences between AA and CRC is critical. METHODS: We performed retrospective analyses of AA patients (N = 266) with tumour and/or blood next-generation sequencing (NGS) (2013-2018) with in-depth clinicopathological annotation. Overall survival (OS) was examined. For comparison, CRC cohorts annotated for sidedness, consensus molecular subtypes (CMS) and mutations (N = 3283) were used. RESULTS: Blood-NGS identified less RAS/GNAS mutations compared to tissue-NGS (4.2% vs. 60.9%, P < 0.0001) and showed poor concordance with tissue for well-/moderately differentiated tumours. RAS (56.2%), GNAS (28.1%) and TP53 (26.9%) were most frequent mutations. Well/moderately differentiated tumours harboured more RAS (69.2%/64.0% vs. 40.5%) and GNAS (48.7%/32.0% vs. 10.1%) while moderate/poorly differentiated tumours had more TP53 (26.0%/27.8% vs. 7.7%) mutations. Appendiceal adenocarcinoma (compared to CRC) harboured significantly fewer APC (9.1% vs. 55.4%) and TP53 (26.9% vs. 67.5%) and more GNAS mutations (28.1% vs. 2.0%) (P < 0.0001). Appendiceal adenocarcinoma mutation profile did not resemble either right-sided CRC or any of the four CMS in CRC. High grade, but no mutation, was independently predictive of survival. CONCLUSION: Integrated clinico-molecular profiling of AA identified key molecular drivers distinct from CRC. Appendiceal adenocarcinoma has a predominantly grade-driven biology that trumps mutations.

Sarcomatoid carcinoma presenting as cancers of unknown primary: a clinicopathological portrait.

BACKGROUND: Sarcomatoid carcinoma of unknown primary (SCUP) is a rare entity of either poorly differentiated carcinoma with sarcoma-like differentiation or a true mixed lineage neoplasm. Limited data regarding clinicopathological profile and management exists. METHODS: We retrospectively reviewed the MD Anderson Cancer of Unknown Primary database and tumor registry to identify 48 SCUP patients between 2001 and 2017. Patient characteristics, pathology, molecular diagnostics, treatments, and outcomes were obtained. Kaplan-Meier method was used to estimate overall survival (OS) and compared using log rank test. RESULTS: Median age at diagnosis was 59 years (range 27-86). Majority of patients were female (58%) and presented with ≥3 metastatic sites (52%), commonly lymph node (50%), bone (42%), lung (27%), and liver (21%). First line treatment included chemotherapy (35%), surgery (27%), and radiation (24%). Gemcitabine and docetaxel (18%) was the most common chemotherapy regimen. Median OS for entire cohort was 11 months (95% CI: 5.6 to 16.4). Poor performance status (PS), > 1 metastatic site, elevated lactate dehydrogenase (LDH), and high neutrophil-to-lymphocyte ratio (NLR) were significantly associated with worse OS on univariate analyses. On multivariate analyses, poor PS (HR 8.7; 95%CI: 3.0-25.0; p <  0.001) and high NLR (HR 3.4; 95%CI: 1.3-8.8; p = 0.011) emerged as independent prognostic factors for OS. CONCLUSIONS: SCUP is a rare presentation with an aggressive clinical course and limited survival. Diagnosis is difficult to make and requires careful review and synthesis of histology, immunohistochemistry, and molecular diagnostics. Chemotherapy resistance remains a challenge. Early mutational profiling is warranted, and clinical trial participation should be encouraged for this subset.

Risk of peritoneal metastases in patients who had negative peritoneal staging and received therapy for localized gastric adenocarcinoma.

BACKGROUND: Positive peritoneal cytology (+PCyt) or gross carcinomatosis (GPC) carries a poor prognosis. Laparoscopic staging to detect +PCyt/GPC is recommended for all ≥T1b gastric adenocarcinoma (GAC). The natural history of patients with GAC who have baseline -PCyt and then undergo multimodality therapy is not well documented, particularly for the risk of subsequent GPC. METHODS: We identified 238 GAC patients with baseline -PCyt who were followed for the development of peritoneal carcinomatosis (PC). Standard statistical methods were employed. RESULTS: Of 238 patients, 192 had attempted surgery after preoperative therapy. Of these, 13 patients (6.8%) had GPC and one had liver metastases, thus surgery was aborted. We followed 164 patients who had an R0 resection. The median follow-up duration was 3.4 (range, 0.6-18) years. The rate of PC was 13.4%, (22/164 patients) and the median time to PC was 15.6 months. Female gender was associated with PC on multivariate analysis. The 5-year OS rate for patients without subsequent PC was 75%. Conclusion Even with baseline -Cyt, ∼25% of patients develop PC following multimodality therapy. Patients who do not develop PC have an excellent OS rate. Further research is warranted to detect PC at baseline by the use of biomarkers.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Moderately and Poorly Differentiated Appendiceal Adenocarcinoma: Survival Outcomes and Patient Selection.

BACKGROUND: Moderately and poorly differentiated adenocarcinoma of the appendix represents an aggressive histological variant with a high risk of recurrence and death. METHODS: Overall, 178 patients with moderately and poorly differentiated appendiceal adenocarcinoma were identified from a prospective database. Clinical, pathologic, and treatment factors were analyzed for outcomes. RESULTS: Diagnostic laparoscopy (DL) identified radiographic occult peritoneal metastasis in 25 (42%) patients. These patients had a significantly lower peritoneal carcinomatosis index (PCI) and improved overall survival (OS) compared with those with radiographic disease. Twenty-seven (41%) patients were excluded from cytoreductive surgery (CRS) because of findings on DL, while 116 (65%) patients underwent CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), with a median disease-free survival (DFS) of 23 months. Mucinous histology (hazard ratio [HR] 0.52, p = 0.04) and PCI (HR 1.054, p = 0.02) were independent predictors of DFS. The median OS following CRS and HIPEC was 48 months. Mucinous histology (HR 0.352, p = 0.018), signet ring cells (HR 3.34, p = 0.02), positive peritoneal cytology (HR 0.081, p = 0.04), and PCI (HR 1.076, p = 0.004) were independently associated with OS. Eight-five (73.3%) patients received neoadjuvant chemotherapy, and 40 (47.1%) patients achieved a radiographic response; 36 (42.3%) had stable disease, while 9 (10.6%) had progressive disease. Stable or responsive disease was associated with improved median OS of 44 months, compared with 21 months for those with progressive disease (p = 0.011). CONCLUSIONS: In selected patients, long-term survival can be obtained. Mucinous histology, absence of signet ring cells, negative peritoneal cytology, PCI ≤ 20, and response/stable disease after neoadjuvant chemotherapy are important selection criteria for CRS and HIPEC.

Utility of Appendiceal Calcifications Detected on Computed Tomography as a Predictor for an Underlying Appendiceal Epithelial Neoplasm.

BACKGROUND: Mucinous appendiceal neoplasms can contain radiopaque calcifications. Whether appendiceal radiographic calcifications indicate the presence of an appendiceal epithelial neoplasm is unknown. This study aimed to determine whether appendiceal calcifications detected by computed tomography (CT) correlate with the presence of appendiceal epithelial neoplasms. METHODS: From prospective appendiceal and pathology databases, 332 cases of appendiceal neoplasm and 136 cases of control appendectomy were identified, respectively. Only cases with preoperative CT scans available for review were included in the study. Images were reviewed by two abdominal radiologists. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were calculated, and the kappa statistic was used to determine agreement between the radiologists' interpretations. RESULTS: Interobserver agreement between the radiologists was substantial, with a kappa of 0.74. Appendiceal mural calcifications were identified on CT scans in 106 appendiceal neoplasm cases (32%) and in 1 control case (1%) (P = 0.0001). In the appendiceal neoplasm subgroup, the presence of radiographic calcifications was associated with mucinous histology (35% vs 17%; P = 0.006; odds ratio [OR], 0.38; 95% confidence interval [CI], 0.18-0.78) and with well-differentiated histologic grade (40% vs 24%; P = 0.002; OR, 0.47; 95% CI, 0.29-0.76). The findings showed a sensitivity of 31.9% (95% CI, 26.9-37.2%), a specificity of 99.3% (95% CI, 96-100%), a PPV of 99.1% (95% CI, 94.9-100%), and an NPV of 37.4% (95% CI, 32.4-42.6%). CONCLUSION: This case-control study showed that appendiceal mural calcifications detected on CT are associated with underlying appendiceal epithelial neoplasms and that the identification of incidental mural appendiceal calcifications may have an impact on decisions regarding surgical intervention.

Co-morbidities Rather than Age Impact Outcomes in Patients Receiving Preoperative Therapy for Gastroesophageal Adenocarcinoma.

BACKGROUND: Older patients with localized gastric adenocarcinoma (LGAC) have substantial postoperative morbidity and mortality; however, postoperative outcomes of the patients who receive preoperative chemotherapy and/or chemoradiation have not been reported. We examined the impact of age at baseline on potential predictors of postoperative outcomes. METHODS: Patients with LGAC who were treated with chemotherapy and/or chemoradiation followed by surgery (n = 203) formed two groups: (1) ≥65 years old (n = 70) and (2) <65 years old (n = 133). We assessed postoperative morbidity and mortality as well as overall survival (OS) and progression-free survival (PFS). Potential predictors of 90-day postoperative outcomes were identified i) by age groups and ii) other clinical covariates. Descriptive statistics and survival analyses were utilized. RESULTS: 90-day postoperative morbidity was similar in older and younger patients (61 % vs 58 %; P = 0.655). 90-day mortality was similar (3 % vs 0 %; P = 0.118). Major Clavien grade III/IV complications were similar (17 % vs 12 %; P = 0.392). OS and PFS were also similar for both groups (P = 0.863 and P = 0.558, respectively). Other factors, such as Charlson comorbidity index (P < 0.001) and median operative time (P = 0.002) were strongly associated with postoperative complications. CONCLUSION: Our data show that older patients with LGAC generally have similar outcomes as do younger patients after preoperative therapy but comorbidity indices have significant impact on complications and the long-term outcomes rather than age.

101 Long-Term Survivors Who Had Metastatic Gastroesophageal Cancer and Received Local Consolidative Therapy.

BACKGROUND: Through a multidisciplinary decision-making process, we developed a strategy of systemic therapy followed by local consolidative therapy (chemoradiation with/without surgery) in selected patients with metastatic gastroesophageal carcinoma (mGEAC). Only after a consensus during multidisciplinary discussions, local therapy was initiated. METHODS: We identified 101 patients with mGEAC who had local consolidation. We evaluated the association between various clinical variables (location of the primary, location of metastases, duration of initial chemotherapy, histologic grade, and radiation dose) and overall survival (OS). RESULTS: Of 101 patients, 71 had a proximal primary (esophageal, Siewert type I or II), and 30 patients had a distal primary (Siewert type III or distal). The median OS was 25.7 months (95% confidence interval [CI] 22.3-32.8). The OS rates at 2 and 5 years were 53.8% (95% CI 44.7-64.8) and 20.7% (95% CI 13.4-31.9), respectively. OS was highly associated with the location of the primary (median of 22.8 months for Siewert I/II vs. 41.5 months for Siewert III or distal, p = 0.03). The duration of initial chemotherapy was highly associated with OS (median of 21.8 months for <3 months vs. 32.5 months for ≥3 months, p = 0.004). CONCLUSION: Some mGEAC patients with a favorable clinical course can achieve a ∼20% 5-year survival rate with an approach that uses initial chemotherapy followed by multidisciplinary discussion to proceed with consolidation with local therapy. Patients with distal GEAC and those who receive initial chemotherapy for ≥3 months are the maximum beneficiaries.

Postoperative Morbidity and Mortality Rates are Not Increased for Patients with Gastric and Gastroesophageal Cancer Who Undergo Preoperative Chemoradiation Therapy.

BACKGROUND: This study aimed to determine whether postoperative morbidity and mortality rates increased after preoperative chemoradiation in patients who underwent gastrectomy. METHODS: The medical records of 7404 patients with gastric or gastroesophageal cancer seen from January 1995 to August 2012 were reviewed to identify patients who underwent gastrectomy. χ (2) and logistic regression analysis were used to determine differences in the 90-day postoperative morbidity and mortality rates of patients who underwent upfront surgery (SURG), preoperative chemotherapy (CHEMO), or preoperative chemoradiation (CHEMOXRT). RESULTS: Of the 500 patients included in this study, 200 underwent SURG, 65 had CHEMO, and 235 had CHEMOXRT. Respectively, 33, 43, and 58 % of these patients underwent total gastrectomy (p < 0.01). Resection of other organs was performed respectively in 19, 26, and 23 % of the patients (p = 0.37). Minor complications within 90 days (Clavien-Dindo 1 or 2) occurred for 41 % of the SURG patients, 43 % of the CHEMO patients, and 45 % of the CHEMOXRT patients (p = 0.68). Major complications or death within 90 days (Clavien-Dindo 3, 4, or 5) occurred for 21, 28, and 29 % of the patients, respectively (p = 0.15). The 90-day mortality (Clavien-Dindo 5) rates were 2 % for the SURG patients, 6 % for the CHEMO patients, and 3 % for the CHEMOXRT patients (p = 0.25). The median hospital stays were respectively 12, 12, and 13 days (p = 0.09). In the multivariate analysis, male sex, gastroesophageal junction cancer, total gastrectomy, and resection of other organs were associated with increased major morbidity and mortality rates, whereas preoperative therapy was not. CONCLUSIONS: The CHEMOXRT patients had postoperative morbidity and mortality rates similar to those for the SURG and CHEMO patients.

The Proportion of Signet Ring Cell Component in Patients with Localized Gastric Adenocarcinoma Correlates with the Degree of Response to Pre-Operative Chemoradiation.

BACKGROUND: Patients with localized gastric adenocarcinoma (LGAC), who get pre-operative therapy, have heterogeneous/unpredictable outcomes. Predictive clinical variables/biomarkers are not established. METHODS: We analyzed 107 LGAC patients who had chemoradiation and surgery. LGACs were grouped for (1) presence/absence of signet ring cell histology (SRC) and (2) histologic grade: G2 or G3. %SRC was assessed (0, 1-10, 11-49, and 50-100%) and correlated with pathologic complete response (pathCR) or

Metastatic Gastroesophageal Adenocarcinoma Patients Treated with Systemic Therapy Followed by Consolidative Local Therapy: A Nomogram Associated with Long-Term Survivors.

OBJECTIVE: Patients with metastatic gastroesophageal adenocarcinoma (MGEAC) have a poor but heterogeneous clinical course. Some patients have an unusually favorable outcome. We sought to identify clinical variables associated with more favorable outcomes. METHODS: Of 246 patients with MGEAC, we identified 64 who received systemic therapy and eventually received local consolidation therapy. Univariate and multivariate Cox regression models were used, and a nomogram was developed. RESULTS: Of these 64 patients, 61% had received consolidation chemoradiation (CRT) with doses of 50-55 Gy and 78% did not undergo surgery. The median follow-up time of survivors was 3.9 years, and the median overall survival (OS) from CRT start was 1.5 years (95% CI, 1.2-2.2). Surgery (as local consolidation) was an independent prognosticator for longer OS in the multivariate analysis (p = 0.02). The 5-year OS rate was 25% (SE = 6%). The contributors to the nomogram were longer duration of systemic therapy before CRT and the type of local therapy. CONCLUSIONS: Our data suggest that a subset of patients with MGEAC have an excellent prognosis (OS >5 years). However, these patients need to be identified during their clinical course so that local consolidation (CRT, surgery, or both) may be offered.

A Simplified Preoperative Assessment Predicts Complete Cytoreduction and Outcomes in Patients with Low-Grade Mucinous Adenocarcinoma of the Appendix.

BACKGROUND: Complete cytoreduction with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been shown to improve survival in patients with low-grade mucinous adenocarcinoma (LGMA). However, incomplete cytoreduction exposes patients to significant morbidity without a similar survival benefit. Preoperative assessment of the ability to achieve CRS is therefore a critical step in selecting patients for CRS/HIPEC. OBJECTIVE: The aim of this study was to develop and validate a preoperative scoring system to accurately predict the ability to achieve complete cytoreduction in patients with LGMA of the appendix. METHODS: A simplified preoperative assessment for appendix tumor (SPAAT) score was developed based on computed tomography scan findings thought to predict incomplete cytoreduction. We applied the SPAAT score to patients with LGMA to determine the ability of the score to predict complete cytoreduction. This scoring system was then applied to a separate cohort of patients from a different institution. Sensitivity and specificity were determined for the SPAAT score. Survival was calculated and correlated with the SPAAT score and the completeness of cytoreduction score. RESULTS: A SPAAT score of <3 is a significant predictor of complete cytoreduction in the derivation cohort. In the validation cohort, 40 of 42 patients with a SPAAT score <3 achieved a complete cytoreduction, for a positive predictive value of 95.2 % and a negative predictive value of 100 %. Additionally, the SPAAT score was a significant predictor of disease-free survival. CONCLUSIONS: The SPAAT score is a useful tool in the preoperative assessment of patients with LGMA who are under consideration for cytoreductive surgery. Prospective analysis of this scoring system is warranted to appropriately select patients who will benefit from CRS/HIPEC.

Early versus Delayed Therapy of Advanced Gastric Cancer Patients--Does It Make a Difference?

BACKGROUND: Nearly 50% of gastric cancer patients are diagnosed with advanced gastric cancer (AGC). Therapy is palliative but results in ill effects. The median overall survival (OS) of AGC patients is often <12 months. It is unclear if the early initiation of therapy in all AGC patients is beneficial. METHODS: A retrospective analysis of AGC patients in our database was carried out. The patients were divided into two groups: asymptomatic or symptomatic. We sought to assess whether the delay of systemic therapy was harmful in asymptomatic patients. RESULTS: A total of 135 patients were analyzed. Most patients were symptomatic (68%), males (67%), and had low ECOG scores (0-1; 85%). In univariate analyses, ECOG performance status 0 (p = 0.005), delayed initiation of therapy (p = 0.03), and lack of symptoms (p = 0.03) were associated with a longer OS. The multivariate model for OS identified only ECOG performance status as an independent prognosticator of longer OS (p = 0.02). Asymptomatic patients who had delayed (≥ 4 weeks) systemic therapy had an OS rate of 77% at 1 year compared to 58% for patients treated within 4 weeks (p = 0.47). CONCLUSION: Symptomatic AGC patients had a poor outcome compared to asymptomatic AGC patients. Treatment delay in asymptomatic patients had no detrimental effect on OS, suggesting that the timing of therapy can be based on patient selection.

Initial Standardized Uptake Value of Positron Emission Tomography Influences the Prognosis of Patients with Localized Gastric Adenocarcinoma Treated Preoperatively.

BACKGROUND: In patients with localized gastric adenocarcinoma (LGAC) who receive preoperative therapy, tools to predict response or prognosticate outcome before therapy are lacking. We used initial standardized uptake value (iSUV) of positron emission tomography (PET) to evaluate its association with overall survival (OS). METHODS: We identified 60 patients with confirmed LGAC who were treated with preoperative chemoradiation and had a baseline PET in addition to other routine staging. Fisher's exact test and Wilcoxon's rank sum test were used to determine the association between iSUV and other variables, and the log-rank test and Cox proportional hazards model were used for survival analysis. RESULTS: The median iSUV was 6 (range, 0-28). The presence of signet ring cells in pretreatment biopsies correlated highly with low iSUV (≤ 6; p = 0.0017). Patients with a high iSUV (> 6) had a longer OS compared to those with a low iSUV (≤ 6; p = 0.0344). iSUV was not an independent predictor (p = 0.12); however, the risk of death was reduced for patients with an iSUV > 6 (hazard ratio = 0.26). CONCLUSION: Our novel findings show that among LGAC patients treated with preoperative chemoradiation and surgery, those with a high iSUV have longer OS than patients with a low iSUV. iSUV appears to have a predictive role in patients with LGAC when treated with preoperative chemoradiation.

Molecular biomarkers in gastric cancer.

Gastric cancer (GC) represents a serious health problem on a global scale. Despite some recent advances in the field, the prognosis in metastatic GC remains poor. Even in localized disease the adjunctive therapies improve overall survival (OS) by only approximately 10%. A better understanding of molecular biology, which would lead to improved treatment options, is needed and is the basis for this review. Many potential biomarkers of prognostic significance have been identified, including ALDH, SHH, Sox9, HER2, EGFR, VEGF, Hippo/YAP, and MET. However, inhibition of only HER2 protein has led to a modest survival benefit. A new approach to GC treatment, which is a disease influenced by inflammation, is the exploitation of the immune system to fight disease. Two interesting targets/prognostic markers that bear further investigation in GC are PD1 and PDL, particularly given their success in the treatment of other inflammation/immune-associated malignancies.

Long-term survival in patients with metastatic gastric and gastroesophageal cancer treated with surgery.

BACKGROUND: The purpose of this study was to determine the survival of patients with metastatic gastric cancer treated with surgery. METHODS: We reviewed the medical records of 7,404 patients with gastric or gastroesophageal cancer seen from January 1995 to August 2012 at MD Anderson Cancer Center and identified patients with stage IV disease treated with surgery. Kaplan-Meier curves were created to compare overall survival (OS) between groups. RESULTS: Of the 82 patients who met inclusion criteria, sites of metastatic disease included peritoneum (N = 34, 42%), positive cytology only (N = 17, 21%), distant lymph nodes (N = 12, 15%), and distant organs (N = 19, 23%). The median time from initial cancer diagnosis to surgery for metastatic disease was 10 months (range, 0-70). Surgery included exploratory surgery only (N = 16, 20%), primary tumor resection with or without resection of distant disease (N = 50, 61%), and distant disease resection only (N = 16, 20%). Median follow-up for living patients was 3 years (range, 0.1-14). Median survival for all patients was 1.5 years (range, 0.1-14). Five year OS for patients with peritoneal metastases, positive cytology only, distant lymph nodes, and distant organ involvement was 13, 42, 20, and 34%, respectively. CONCLUSIONS: Surgery in the setting of metastatic disease is an uncommon clinical scenario and has a considerable risk of exploration without resection, although long-term survival is possible.

Feasibility and value of genomic profiling in cancer of unknown primary: real-world evidence from prospective profiling study.

Real-world evidence regarding the value of integrating genomic profiling (GP) in managing cancer of unknown primary (CUP) is limited. We assessed this clinical utility using a prospective trial of 158 patients with CUP (October 2016-September 2019) who underwent GP using next-generation sequencing designed to identify genomic alterations (GAs). Only 61 (38.6%) patients had sufficient tissue for successful profiling. GAs were seen in 55 (90.2%) patients of which GAs with US Food and Drug Administration-approved genomically matched therapy were seen in 25 (40.9%) patients. A change in therapy was recommended and implemented (primary endpoint of the study) in 16 (10.1%) and 4 (2.5%) patients of the entire study cohort, respectively. The most common reason for inability to implement the profiling-guided therapy was worsening of performance status (56.3%). Integrating GP in management of CUP is feasible but challenging because of paucity of tissue and aggressive natural history of the disease and requires innovative precision strategies.

Efficacy of Systemic Chemotherapy in Patients With Low-grade Mucinous Appendiceal Adenocarcinoma: A Randomized Crossover Trial.

Importance: Appendiceal adenocarcinoma is a rare tumor, and given the inherent difficulties in performing prospective trials in such a rare disease, there are currently minimal high-quality data to guide treatment decisions, highlighting the need for more preclinical and clinical investigation for this disease. Objective: To prospectively evaluate the effectiveness of fluoropyrimidine-based systemic chemotherapy in patients with inoperable low-grade mucinous appendiceal adenocarcinoma. Design, Setting, and Participants: This open-label randomized crossover trial recruited patients at a single tertiary care comprehensive cancer center from September 2013 to January 2021. The data collection cutoff was May 2022. Enrollment of up to 30 patients was planned. Eligible patients had histological evidence of a metastatic low-grade mucinous appendiceal adenocarcinoma, with radiographic imaging demonstrating the presence of mucinous peritoneal carcinomatosis and were not considered candidates for complete cytoreductive surgery. Key exclusion criteria were concurrent or recent investigational therapy, evidence of bowel obstruction, and use of total parenteral nutrition. Data were analyzed from November 2021 to May 2022. Interventions: Patients were randomized to either 6 months observation followed by 6 months of chemotherapy, or initial chemotherapy followed by observation. Main Outcomes and Measures: The primary end point was the percentage difference in tumor growth in treatment and observation groups. Key secondary end points included patient-reported outcomes in the chemotherapy and observation periods, objective response rate, rate of bowel complications, and differences in overall survival (OS). Results: A total of 24 patients were enrolled, with median (range) age of 63 (38 to 82) years, and equal proportion of men and women (eg, 12 men [50%]); all patients had ECOG performance status of 0 or 1. A total of 11 patients were randomized to receive chemotherapy first, and 13 patients were randomized to receive observation first. Most patients (15 patients [63%]) were treated with either fluorouracil or capecitabine as single agent; 3 patients (13%) received doublet chemotherapy (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin or folinic acid, fluorouracil, and irinotecan hydrochloride), and bevacizumab was added to cytotoxic chemotherapy for 5 patients (21%). Fifteen patients were available to evaluate the primary end point of difference in tumor growth during treatment and observation periods. Tumor growth while receiving chemotherapy increased 8.4% (95% CI, 1.5% to 15.3%) from baseline but was not significantly different than tumor growth during observation (4.0%; 95% CI, -0.1% to 8.0%; P = .26). Of 18 patients who received any chemotherapy, none had an objective response (14 patients [77.8%] had stable disease; 4 patients [22.2%] had progressive disease). Median (range) OS was 53.2 (8.1 to 95.5) months, and there was no significant difference in OS between the observation-first group (76.0 [8.6 to 95.5] months) and the treatment-first group (53.2 [8.1 to 64.1] months; hazard ratio, 0.64; 95% CI, 0.16-2.55; P = .48). Patient-reported quality-of-life metrics identified that during treatment, patients experienced significantly worse fatigue (mean [SD] score, 18.5 [18.6] vs 28.9 [21.3]; P = .02), peripheral neuropathy (mean [SD] score, 6.67 [12.28] vs 38.89 [34.88]; P = .01), and financial difficulty (mean [SD] score, 8.9 [15.2] vs 28.9 [33.0]; P = .001) compared with during observation. Conclusions and Relevance: In this prospective randomized crossover trial of systemic chemotherapy in patients with low-grade mucinous appendiceal adenocarcinoma, patients did not derive clinical benefit from fluorouracil-based chemotherapy, given there were no objective responses, no difference in OS when treatment was delayed 6 months, and no difference in the rate of tumor growth while receiving chemotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01946854.