Surgical Resection Of Primary Tumor Research Articles

Surgical Resection of Primary Tumors Provides Survival Benefits for Lung Cancer Patients With Unexpected Pleural Dissemination

Background: Surgery is not generally recommended for non-small cell lung cancer (NSCLC) patients with malignant pleural dissemination (PD). However, in some cases, PD is found unexpectedly during surgery. There is no consensus on whether surgical intervention can provide survival benefit for them. We investigated the role of surgery in NSCLC patients with unexpected PD by a cohort study.Methods: Clinical data of consecutive patients who intended to undergo radical surgery for NSCLC between January 2010 and December 2015 at Shanghai Chest Hospital and Huadong Hospital were collected from a lung cancer database. Patients diagnosed with unexpected malignant pleural nodules intraoperatively were enrolled in this retrospective study.Results: A total of 181 NSCLC patients were diagnosed with unexpected malignant PD intraoperatively and confirmed with postoperatively histological examinations. Out of these, 80 (44.2%) patients received pleural nodule biopsies alone, and 101 (55.8%) received primary tumor resection (47 with sublobar resection and 54 with lobectomy). The median progression-free survival and overall survival for all patients were 13 and 41 months respectively. Patients in the resection group had significantly better progression-free survival (19.0 vs. 10.0 months, P < 0.0001) and overall survival (48.0 vs. 33.0 months, P < 0.0001) than patients in the biopsy group. In the resection group, there was no statistical difference between patients with sublobar resection and lobectomy (P = 0.34). Univariate and multivariate analyses identified primary tumor resection, targeted adjuvant therapy, and tumor size (≤ 3 cm) as independent prognostic factors.Conclusions: NSCLC patients with unexpected intraoperative PD potentially benefited from surgical resection of the primary tumor and multidisciplinary targeted therapy, particularly when tumor size did not exceed 3 cm. Our data demonstrated that the resection type was not associated with survival differences, which remains to be defined with a larger sample size.

Surgical resection of primary tumor in the extremities improves survival for metastatic soft-tissue sarcoma patients: a population-based study of the SEER database.

The objectives of this study were to clarify whether resection of primary tumor in the extremities for patients with metastatic soft-tissue sarcoma (STS) improves survival, and to clarify patient groups for whom primary tumor resection should be considered. Using the surveillance, epidemiology, and end results database, we identified 1453 patients with metastatic STS of the extremities at initial presentation between 1983 and 2016. Of these 1453 patients, 898 patients underwent primary tumor resection (Surgery group), and 555 patients did not (No-surgery group). After adjusting for patient background by propensity score matching, a total of 804 patients were included for analysis. Patients in the Surgery group showed improved survival (cancer-specific survival (CSS) hazard ratio (HR) = 0.59, 95% confidence interval (CI) 0.50-0.71 overall survival rate (OS) HR = 0.60, 95% CI 0.51-0.70). In subclass analysis, patients with high-grade STS, undifferentiated pleomorphic sarcoma, leiomyosarcoma, or synovial sarcoma showed improved survival in the Surgery group (high grade-CSS HR = 0.57, 95% CI 0.45-0.72, OS HR = 0.58, 95% CI 0.48-0.71; undifferentiated pleomorphic sarcoma-CSS HR = 0.60, 95% CI 0.42-0.84, OS HR = 0.61, 95% CI 0.46-0.82; leiomyosarcoma-CSS HR = 0.50, 95% CI 0.33-0.75, OS HR = 0.50, 95% CI 0.35-0.72; synovial sarcoma-CSS HR = 0.46, 95% CI 0.31-0.68, OS HR = 0.43, 95% CI 0.30-0.62). Our results indicated that primary tumor resection in metastatic STS exerts positive impacts on survival. Further clinical research is needed to confirm these results.

Case Analysis of 14 Children with Malignant Rhabdoid Tumor of the Kidney.

ObjectiveThis study aims to summarize the clinical features and prognoses of the malignant rhabdoid tumor of the kidney (MRTK) in children. It further aims to analyze the high-risk factors affecting MRTK prognosis.MethodsClinical data from 14 children with MRTK treated in Paediatrics of Beijing Tongren Hospital from January 2010 to December 2019, along with the high-risk factors affecting prognosis, were retrospectively analyzed.ResultsThere were 14 children with MRTK included in the study, with a median onset age of 13 (3–46) months. Thirteen patients had distant metastases, the most common site for metastases being inside the lung. A comprehensive treatment protocol combined with chemotherapy was mainly applied during the surgery. A surgical resection of primary tumors was performed on 13 (13/14) patients, and all 14 children received chemotherapy with ifosfamide + carboplatin + etoposide, ifosfamide + etoposide, and vincristine + pirarubicin + cyclophosphamide regimens, alternately. Three patients received radiotherapy and two received oral targeted drugs after partial response. The median follow-up was after 16.5 months (3–53 months) and the four-year overall survival (OS) was 41.8%. In children aged ≤24 months and children aged >24 months, the two-year OS was 67.2% and 100% (χ2 = 108.998, P<0.05), respectively. In children with Ki 67 > 70% and children with Ki 67 < 70%, the two-year OS was 52.6% and 86.9% (χ2 = 8.544, P = 0.003), respectively. In children with distant metastases and children without distant metastasis, the two-year OS was 70% and 100% (χ2 = 14.239, P<0.05), respectively.ConclusionThe most common MRTK distant metastasis site is the lung. Risk factors for poor MRTK prognoses include an age of <24 months, Ki 67 > 70%, and distant metastases.

Impact of surgical resection on survival in patients with metastatic soft tissue sarcoma and comparison between synchronous and metachronous metastases

BackgroundThe role of local surgery in patients with metastatic soft tissue sarcoma (STS) remains unknown. The study aims to assess the clinical outcomes and impact of surgical resection on survival in patients with metastatic STS and elucidate the survival differences between synchronous and metachronous metastatic groups. MethodsAmong the 272 patients with STS treated between 2000 and 2018, 84 with synchronous or metachronous metastasis were included. Associations between overall survival and primary tumor resection and metastasectomy were assessed using multivariate Cox regression analyses to adjust for baseline differences between surgically and non-surgically treated patients. Propensity score matching was applied to compare synchronous and metachronous metastasis. ResultsAmong the 84 patients included, 69 (82%) and 41 (49%) underwent primary tumor resection and metastasectomy, respectively. The 2- and 5-year overall survivals of all patients after first detection of metastasis were 51.1% and 24.4%, respectively. Multivariate analysis showed that size <8 cm, grade <3, and number of metastases <4 were associated with longer overall survival. After adjusting for baseline demographic and tumor characteristics, primary tumor resection and metastasectomy still had favorable effects on survival. Tumor subtypes, grade, and number of metastases differed significantly between synchronous and metachronous groups. However, after adjusting for these valuables, both groups exhibited comparable survival. ConclusionsApproximately one fourth of the patients with metastatic STS survived for >5 years. Our results showed that surgical resection of primary tumors or metastatic lesions had favorable impact on survival even after adjusting for patient backgrounds, with comparable survival observed between those with synchronous and metachronous metastases.

Surgical resection of primary tumors improved the prognosis of patients with bone metastasis of non-small cell lung cancer: a population-based and propensity score-matched study.

BackgroundMost patients with lung cancer are in an advanced stage at the time of diagnosis due to occult onset. Bone is one of the most common sites of hematogenous metastasis of lung cancer. This study aimed to evaluate the impact of surgical resection of primary tumors on the prognosis of patients with bone metastasis of non-small cell lung cancer, using the Surveillance, Epidemiology, and End Results (SEER) database.MethodsA total of 9,804 patients with only bone metastasis were identified from the SEER database. Propensity score matching was used to reduce the selection bias. Cancer-specific survival (CSS) and overall survival (OS) were compared between patients with or without primary tumor resection. The Cox regression model was applied to evaluate multiple prognostic factors.ResultsAfter propensity score matching, 424 patients were selected for survival analysis. No statistically significant differences were found in age, sex, race, tumor location, histology, T stage, and N stage between patients with or without surgical resection of primary tumors. The prognosis of patients who underwent surgical resection of primary tumors was significantly better than that of patients who had not undergone surgery. The surgical resection of primary tumors was an independent prognostic factor. The prognosis of patients who underwent lobectomy/bilobectomy was significantly better compared to other surgical types. Regional lymph node resection during surgery also significantly improved the prognosis of the patients.ConclusionsFor patients with only bone metastasis, surgical resection of primary tumors could significantly improve prognosis. Lobectomy/bilobectomy with regional lymph node resection was the best surgical strategy.

Combination of Bempegaldesleukin and Anti-CTLA-4 Prevents Metastatic Dissemination After Primary Resection or Radiotherapy in a Preclinical Model of Non-Small Cell Lung Cancer.

Surgical resection or hypo-fractionated radiation therapy (RT) in early-stage non-small cell lung cancer (NSCLC) achieves local tumor control, but metastatic relapse remains a challenge. We hypothesized that immunotherapy with anti-CTLA-4 and bempegaldesleukin (BEMPEG; NKTR-214), a CD122-preferential IL2 pathway agonist, after primary tumor RT or resection would reduce metastases in a syngeneic murine NSCLC model. Mice bearing Lewis Lung Carcinoma (LLC) tumors were treated with combinations of BEMPEG, anti-CTLA-4, and primary tumor treatment (surgical resection or RT). Primary tumor size, mouse survival, and metastatic disease at the time of death were assessed. Flow cytometry, qRT-PCR, and cytokine analyses were performed on tumor specimens. All mice treated with RT or surgical resection of primary tumor alone succumbed to metastatic disease, and all mice treated with BEMPEG and/or anti-CTLA-4 succumbed to primary tumor local progression. The combination of primary tumor RT or resection and BEMPEG and anti-CTLA-4 reduced spontaneous metastasis and improved survival without any noted toxicity. Flow cytometric immunoprofiling of primary tumors revealed increased CD8 T and NK cells and decreased T-regulatory cells with the combination of BEMPEG, anti-CTLA-4, and RT compared to RT alone. Increased expression of genes associated with tumor cell immune susceptibility, immune cell recruitment, and cytotoxic T lymphocyte activation were observed in tumors of mice treated with BEMPEG, anti-CTLA-4, and RT. The combination of BEMPEG and anti-CTLA-4 with primary tumor RT or resection enabled effective control of local and metastatic disease in a preclinical murine NSCLC model. This therapeutic combination has important translational potential for patients with early-stage NSCLC and other cancers.

Clinical Outcomes of Metastatic Colorectal Cancer Following Surgical Resection of the Primary tumor at Hiwa Cancer Hospital, Sulaimani, Iraq

Background: Colorectal cancer (CRC) is one of the main causes of cancer-related mortality. The surgical resection of primary CRC tumors is a critical line of treatment. The present study investigated the clinical outcomes of the surgical resection of the primary tumor in metastatic CRC patients. Materials and Methods: In this prospective and retrospective study, 81 metastatic CRC patients were recruited at Hiwa Cancer Hospital in Sulaimani, Iraq from January 2016 to December 2019. Forty-one patients underwent surgical resection of their primary tumor while the remaining 40 patients did not undergo resection. Data regarding patients’ clinical outcomes were obtained from the clinical portal system of the hospital and were analyzed using SPSS (version 23.0). Results: The patients’ mean (± SD) age was 53.5 (± 17.02) years and the male-to-female ratio was 1.3:1. Patients undergoing the surgical resection of their primary tumors had a significantly better one-year survival compared to those who did not undergo resection (P = 0.04). Based on the results, patients in the surgical resection group continued to have a better overall survival although it was not statistically significant (P = 0.1). Significantly more patients with colon cancer underwent surgical resection compared to rectal cancer (P = 0.03), and smoking habit negatively affected the chance to undergo surgical resection (P = 0.009). Conclusion: In general, the surgical resection of the primary tumor has a significant favorable impact on one-year survival, but possibly not on overall survival. The primary site of the tumor and smoking habits significantly influence the chance to undergo surgical resection whereas the grade of the tumor or the type of systemic therapy has no significant impact in this regard.

A machine learning-based radiomics model for the prediction of axillary lymph-node metastasis in breast cancer.

The aim of this study was to develop and validate machine learning-based radiomics model for predicting axillary lymph-node (ALN) metastasis in invasive ductal breast cancer (IDC) using F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). A total of 100 consecutive IDC patients who underwent surgical resection of primary tumor with sentinel lymph-node biopsy and/or ALN dissection without any neoadjuvant treatment were analyzed. Volume of interests (VOIs) were drawn more than 2.5 of standardized uptake value in the primary tumor on the PET scan using 3D slicer. Pyradiomics package was used for the extraction of texture features in python. The radiomics prediction model for ALN metastasis was developed in 75 patients of the training cohort and validated in 25 patients of the test cohort. XGBoost algorithm was utilized to select features and build radiomics model. The sensitivity, specificity, and accuracy of the predictive model were calculated. ALN metastasis was found in 43 patients (43%). The sensitivity, specificity, and accuracy of F-18 FDG PET/CT for the diagnosis of ALN metastasis in the entire patients were 55.8%, 93%, and 77%, respectively. The radiomics model for the prediction of ALN metastasis was successfully developed. The sensitivity, specificity, and accuracy of the radiomics model for the prediction of ALN metastasis in the test cohorts were 90.9%, 71.4%, and 80%, respectively. The machine learning-based radiomics model showed good sensitivity for the prediction of ALN metastasis and could assist the preoperative individualized prediction of ALN status in patients with IDC.

Prognostic Value and Molecular Landscape of HER2 Low-Expressing Metastatic Colorectal Cancer

BackgroundThe prognostic value and molecular landscape of human epidermal growth factor receptor 2 (HER2) low-expressing (HER2-L) metastatic colorectal cancer (mCRC) remain unclear. Patients and MethodsThis study enrolled patients with mCRC who had undergone surgical resection of primary tumor. Using the specimen, we evaluated HER2 expression by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 positivity was defined as follows: HER2 positivity (HER2-Pos) as IHC 3 + or IHC 2+/FISH positive, HER2-L as IHC 2+/FISH negative or IHC 1+, and HER2 negativity (HER2-Neg) as IHC 0+. Gene alterations were determined by next-generation sequencing. ResultsBetween 2005 and 2015, a total of 370 patients were analyzed, comprising 15 patients (4%) with HER2-Pos, 21 (6%) with HER2-L, and 334 (90%) with HER2-Neg disease. The clinicopathologic characteristics among groups had no differences. HER2-L had a significantly higher proportion of coaltered RAS mutation than HER2-Pos (P = .037). With a median follow-up of 101.8 months, HER2-L had a significantly better median overall survival than HER2-Pos (P = .029) (18.2 months in HER2-Pos vs. 33.3 in HER2-L vs. 27.9 in HER2-Neg). In 58 patients harboring wild-type RAS and receiving anti-EGFR antibody therapy, HER2-L had a better median progression-free survival tendency than HER2-Pos, with 2.2 months in HER2-Pos, 7.8 in HER2-L, and 5.1 in HER2-Neg (P = .036). ConclusionHER2-L mCRC showed a better prognosis than HER2-Pos mCRC, and it is similar to HER2-Neg mCRC. Hence, HER2-L mCRC might have different biologic behavior in terms of prognostic value and molecular landscape of mCRC, suggesting the possibility of implementation of HER2-guided clinical development against HER2-expressing mCRC.

Early-onset colorectal cancer in younger patients: A population-based study.

124 Background: In the US, the incidence of colorectal cancer (CRC) is increasing in patients younger than 50 years who may present with advanced stage, high grade, left-sided colon or rectal cancers with signet ring cell histopathology, aggressive clinical course, and reduced overall survival. Understanding the characteristics of this population could inform screening, early detection, and optimal treatment. In this study, we describe the attributes of adults who are 50 years and younger with a first diagnosis of CRC and ascertain molecular testing rates and time to surgery by using data from a commercially insured cohort in the U.S. Methods: This retrospective study of patients ages 50 and younger with a first diagnosis of CRC utilizes the IBM MarketScan database, and focuses on claims from January 2013 to December 2018. Included patients had continuous insurance enrollment of 12 months before and 6 months after diagnosis. We determined rates of tumor testing for microsatellite instability (MSI) or immunohistochemistry (IHC) for mismatch repair (MMR) proteins and referral to genetic services in all patients, as well as mutational analysis of KRAS, NRAS, and BRAF in metastatic CRC patients. Time to surgical resection of primary tumor (TTS) in non-metastatic colon cancer patients was measured. Results: During the 5-year period, 10,577 patients ages 18 to 50 years had a first diagnosis of CRC, which was 15.6% of the 67,921 adults of all ages with CRC. Claims for MSI or IHC for MMR proteins within 120 days of initial diagnosis were done in 4,429 (41.9%) patients and referral to genetics services/counseling within 1 year of initial diagnosis were done in 443 (4.1%) patients. Among metastatic CRC patients, KRAS, NRAS, or BRAF tumor mutational analyses within 120 days of initial diagnosis were documented in 323 (31.5%). The median TTS ranged from 7 to 15 days with no statistically significant differences based on geographic region or health insurance plan type. Conclusions: Younger patients with early onset CRC had low rates of referral to genetics services, tumor MSI or IHC for MMR proteins testing, and KRAS, NRAS, and BRAF mutational analysis. There were no geographic or insurance type trends in TTS in non-metastatic colon cancer patients. Although underreporting is possible in our study, the findings of low utilization of genetic services and tumor genomic testing in these younger patients with early onset CRC should alert the oncology community to critical management gaps in the care of this population.

Stage 4S Neuroblastoma: What Are the Outcomes? A Systematic Review of Published Studies.

The prognosis of stage 4S/MS neuroblastoma has traditionally been reported as excellent, yet conflicting treatment protocols exist for this enigmatic disease. To critically address this question, we have undertaken a systematic review of published studies to accurately determine outcomes for infants with stage 4S/MS neuroblastoma. Studies were identified using MEDLINE, Embase, and Cochrane databases using the relevant search terms. Literature reviews, case reports, and adult studies were excluded. Data were extracted independently following article selection by three authors and reviewed by the senior author. The original search retrieved 2,325 articles. Following application of exclusion criteria and removing duplicate data, 37 studies (1,105 patients) were included for final review. Overall patient survival was 84%. Twelve studies (544 patients) recorded MYCN status. Mortality in MYCN amplified tumors was 56%. Chromosome 1p/11q status was reported in four studies and 1p/11q deletion carried a 40% fatality rate. Management included observation only (201 patients, 8.5% mortality), surgical resection of primary tumor only (153 patients, 6.5% mortality), chemotherapy only (186 patients, 21% mortality), radiotherapy (5 deaths, 33% mortality), chemotherapy with surgery (160 patients, 10% mortality), surgery with radiotherapy (21 patients, 19% mortality), radiotherapy with chemotherapy (42 patients, 29% mortality), and surgery with chemotherapy and radiotherapy (27 patients, 33% mortality). There is a significant mortality observed in stage 4S/MS neuroblastoma infants with a dismal outcome observed in those patients with MYCN amplification and 1p/11q deletion. Those patients suitably amenable for conservative management or surgery to excise the primary tumor carry the best prognosis.

Radical local treatment for stage IV non-small cell lung cancer in older adults: a propensity-score matched analysis of the SEER database.

BackgroundIncreased incidence of lung cancer in older adults is attributed to increased life expectancy, increased risk for many types of cancer, age-associated comorbidities and physical performance status. Contraindicatory tumor resection is suggested to benefit survival outcomes in stage IV non-small-cell lung cancer (NSCLC). We analyzed the clinical characteristics of older adults ≥70 years old with stage IV NSCLC and investigated whether radical local treatment may benefit this population.MethodsThis retrospective, population-based cohort study analyzed patient data from the USA Surveillance, Epidemiology and End Results (SEER) Program during 2004–2016. Eligible patients were aged ≥70 years and diagnosed with stage IV NSCLC. Primary endpoints were overall survival (OS) and lung-cancer-specific survival (LCSS). Propensity-score matching (PSM) and Cox regression analysis were performed to assess the prognostic role of surgical resection of primary tumor or metastasis.ResultsAmong 54,310 stage IV NSCLC older patients, 7.50% received radical local treatment of the primary tumor or metastasis. PSM resulted in a balanced study population consisting of a treatment group (n=4,037) and a matched no-local-treatment group (n=15,658). After adjusting for confounders, radical local treatment was significantly associated with increased LCSS [hazard ratio (HR): 0.85, 95% confidence interval (95% CI): 0.72–1.00] but decreased OS (HR: 1.97, 95% CI: 1.31–2.97, P=0.0012).ConclusionsIn older adults ≥70 years old with stage IV NSCLC, radical local treatment is associated with increased LCSS but decreased OS. Additional prospective studies are warranted to confirm the benefit of radical local treatment for primary or metastatic NSCLC.

Stage-dependent angiopoietin-Tie2 and nitric oxide signaling of erythrocytes in response to surgical trauma in head and neck cancer

BackgroundAngiopoietin-Tie2 and nitric oxide pathway is crucial in tumor angiogenesis and closely correlates with tumor development, growth, and metastasis. This study aimed to investigate the angiopoietin-Tie2 and nitric oxide signaling of the erythrocyte membrane in response to surgical trauma in head and neck cancer.MethodsWe prospectively enrolled the patients with histology-proven head and neck squamous cell carcinoma undergoing surgical resection of primary tumors at the medical center between August and November 2019. We measured the preoperative and postoperative levels of angiopoietin-1, angiopoietin-2 in plasma using enzyme-linked immunosorbent assays, nitric oxide in plasma using nitrate/nitrite colorimetric assays, and Tie2 phosphorylation in erythrocyte membrane using Western blotting.ResultsThe plasma angiopoietin-1 was downregulated from the median 971.3 pg/mL (interquartile range [IQR] 532.1–1569.3) to 417.9 (IQR 270.5–597.3) after tumor resection (p = 0.0020). Conversely, the plasma angiopoietin-2 was enhanced from 1173.6 pg/mL (IQR 977.7–1450.2) to 2353.7 (IQR 1352.4–2954.3) after surgery (p = 0.0021), with a concomitant increase in plasma nitric oxide level from 7.73 μM (IQR 5.39–10.06) to 10.50 (IQR 7.65–14.18) after surgical resection (p = 0.0093). Subgroup analyses further showed the angiopoietin-Tie2 and nitric oxide signaling was significant only in stage III and IV cancer.ConclusionsThe dynamic change of angiopoietin-Tie2 signaling in the erythrocyte membrane along with the enhanced nitric oxide in plasma after tumor resection suggests erythrocytes play a significant role in modulating surgery-induced angiogenesis, which may provide a novel marker for cancer surveillance and control.

Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis

The most common site of breast cancer metastasis is the bone, occurring in approximately 70% of patients with advanced disease. Bone metastasis is associated with severe morbidities and high mortality. Therefore, deeper understanding of the mechanisms that enable bone-metastatic relapse are urgently needed. We report the establishment and characterization of a bone-seeking variant of breast cancer cells that spontaneously forms aggressive bone metastases following surgical resection of primary tumor. We characterized the modifications in the immune milieu during early and late stages of metastatic relapse and found that the formation of bone metastases is associated with systemic changes, as well as modifications of the bone microenvironment towards an immune suppressive milieu. Furthermore, we characterized the intrinsic changes in breast cancer cells that facilitate bone-tropism and found that they acquire mesenchymal and osteomimetic features. This model provides a clinically relevant platform to study the functional interactions between breast cancer cells and the bone microenvironment, in an effort to identify novel targets for intervention.

Survival value of primary tumour resection for stage IV non-small-cell lung cancer: A population-based study of 6466 patients.

For stage IV non-small-cell lung cancer (NSCLC) patients, surgical resection of primary tumour was rarely recommended. We conducted this population-based study to demonstrate the survival value of primary tumour resection (PTR) for stage IV (NSCLC). The Surveillance, Epidemiology and End Results (SEER) database was searched for selecting stage IV NSCLC patients. The patients were matched according to age, gender, grade, primary tumour site, histopathological type, tumour size and regional lymph nodes metastasis by propensity score matching (PSM) analysis. Kaplan-Meier curves were presented to show the survival differences between resection group and non-resection group. Risk factors which were supposed to influence survival outcome were investigated using a Cox proportional hazard regression model. And a nomogram was performed to present prognostic factors for stage IV NSCLC patients. 6466 patients diagnosed from 2004 to 2015 were included in survival analyses after PSM. The median overall survival (OS) for overall patients with resection was 27 months, much longer than those without resection (8 months). And this trend remained in subgroup analyses, including different histopathological types and distant metastases (All P values<0.001). Younger age, race other than white and black, female, grade 1/2 (G1/G2), PTR, chemotherapy, no other distant metastases, smaller tumour size and no regional lymph node metastases were favourable prognostic factors for stage IV NSCLC. A predictive nomogram was conducted based on above risk factors. PTR prolonged survival of stage IV NSCLC patients. And PTR should be considered in clinical practice for stage IV NSCLC.

P-298 Surgical resection of primary tumor as a prognostic factor in stage IV colon adenocarcinoma

Stage IV colon adenocarcinomas represent 22% of all colon cancer cases at diagnosis. There are some known prognostic factors such as left vs right sidedness, microsatellite instability, and KRAS and BRAF mutations. We seek to identify if surgical resection of the primary tumor is a prognostic factor for overall survival (OS). We identified histologically confirmed cases of colon adenocarcinomas with metastatic disease and information about surgery status and OS diagnosed between 2004 and 2016 from the National Cancer Database (NCDB). Kaplan-Meier method and log-rank test were used to estimate and compare OS. Recursive partitioning analysis (RPA) analysis was performed on the entire cohort. 169,001 patients met our inclusion criteria: 102,369 patients underwent surgical resection of the primary tumor and 66,632 patients did not. Surgical status, age, and sidedness were significant prognostic factors for OS by RPA, in that order. Patients who underwent surgery, younger than 75 years, with left-sided tumors had median OS of 30.7 months, compared with patients who did not undergo surgery, were younger than 75 years, with left-sided tumors had a median OS of 14.5 months (p< 0.0001). A similar improvement in OS was seen with patients with right-sided tumors. In the older than 75 years group, patients who underwent surgery had improved median OS of 10.2 months, compared with non-surgery patients who had median OS of 4.1 months (p< 0.0001). Surgical status, age, and sidedness were significant prognostic factors for OS, in that order. Patients who underwent surgery, were younger than 75 years, with left-sided tumors had the best OS.

Clinical investigation on sarcoma in oral and maxillofacial regions: A multicenter retrospective analysis in Japan

The aim of the present study was to review the treatment outcomes of oral sarcoma in Japan based on a multicenter retrospective analysis. Between January 2001 and December 2015, 30 patients were histologically diagnosed with sarcoma in the oral and maxillofacial regions and retrospectively reviewed. Osteosarcoma was the most common in 6 (20 %) out of 30 cases, followed by 3 cases (10 %) of fibrosarcoma. The average maximum size of the primary tumor was 42.3 ± 18.7 mm (range: 5−80 mm). The mandible was the most common site of the primary tumor and observed in 15 cases (50 %), followed by the maxilla in 12 cases (40 %). Soft tissue sarcoma was noted in 3 cases (10 %). The average follow-up period was 5.6 ± 4.6 years (range, 0.1–14.7 years). Five- and 10-year OS rates were 81.4 and 62.0 %, respectively. Five- and 10-year OS rates in cases that underwent radical surgery were 95.5 and 72.7 %, respectively, and were significantly higher than those treated with non-surgical therapy (p < 0.0001). The early detection and complete surgical resection of primary tumors with adequate surgical margins appears to be important for improving the prognosis of oral sarcoma patients.

Surgical resection of primary tumor is associated with prolonged survival in low-grade pancreatic neuroendocrine tumors

The incidence of pancreatic neuroendocrine tumors (PNETs) is increasing over the past few decades. Surgery for low-grade and small PNETs of less than 2cm and N0M0 is still debated. The purpose of this study is to examine the association between surgical resection and survival in patients with low-grade nonfunctioning PNETs. Patients diagnosed with PNETs between 2004 and 2015 were extracted from SEER. Kaplan-Meier methods and Cox proportional hazard models were used to estimate independent predictors in PNETs patients. A total of 2637 patients (2147 underwent surgical resection and 490 did not undergo surgery) with histologically confirmed low-grade PNETs in this cohort study. Overall survival (OS) and cancer-specific survival (CSS) of patients with surgery was better than those without surgery (log rank test POS<0.001, PCSS<0.001). Multivariate Cox regression analysis showed that surgical status was an independent prognostic factor associated with OS (HR 3.257, 95%CI: 2.635, 4.026) and CSS (HR 3.546, 95%CI: 2.798, 4.493). Subgroup analysis suggested the patients receiving surgery apparently had better OS and CSS regardless of tumor size (all log rank test POS<0.001, all log rank test PCSS<0.001) and SEER stage (all log rank test POS<0.001, all log rank test PCSS<0.001), compared to patients without removal of the primary tumor. Surgical resection of primary tumor may have a significant benefit on survival for patients with low-grade nonfunctioning PNETs. To determine the optimal management, grade, stage and tumor size should be considered comprehensively.

Neoadjuvant PD-1 Immune Checkpoint Blockade Reverses Functional Immunodominance among Tumor Antigen-Specific T Cells.

Surgical resection of primary tumor with regional lymphadenectomy remains the treatment of choice for patients with advanced human papillomavirus-negative head and neck squamous cell carcinoma. However, even when pathologic disease-free margins can be achieved, locoregional and/or distant disease relapse remains high. Perioperative immunotherapy may improve outcomes, but mechanistic data supporting the use of neoadjuvant or adjuvant treatment clinically are sparse. Two syngeneic models of oral cavity carcinoma with defined T-cell antigens were treated with programmed death receptor 1 (PD-1) mAb before or after surgical resection of primary tumors, and antigen-specific T-cell responses were explored with functional and in vivo challenge assays. We demonstrated that functional immunodominance developed among T cells targeting multiple independent tumor antigens. T cells specific for subdominant antigens expressed greater levels of PD-1. Neoadjuvant, but not adjuvant, PD-1 immune checkpoint blockade broke immunodominance and induced T-cell responses to dominant and subdominant antigens. Using tumors lacking the immunodominant antigen as a model of antigen escape, neoadjuvant PD-1 immune checkpoint blockade induced effector T-cell immunity against tumor cells lacking immunodominant but retaining subdominant antigen. When combined with complete surgical excision, neoadjuvant PD-1 immune checkpoint blockade led to formation of immunologic memory capable of preventing engraftment of tumors lacking the immunodominant but retaining subdominant antigen. Together, these results implicate PD-1 expression by T cells in the mechanism of functional immunodominance among independent T-cell clones within a progressing tumor and support the use of neoadjuvant PD-1 immune checkpoint blockade in patients with surgically resectable carcinomas.

Molecular landscape and prognostic value of HER2 low-expression on metastatic colorectal cancer.

229 Background: HER2 dual blockade showed the promise in clinical trials in patients (pts) with HER2-positive (HER2-Pos) metastatic colorectal cancer (mCRC). A phase I/II study of a novel anti-HER2 antibody-drug conjugate (HER2-ADC) showed promising activities across different cancer subtypes including HER2-Pos mCRC, and also showed a hint of activity for low-expressing (HER2-L) mCRC, regardless of RAS mutation. However, molecular landscape and prognostic value of HER2-L on mCRC are unclear. Methods: The eligibility included pts with mCRC who had undergone surgical resection of primary tumor. Using the specimen, HER2 expression was evaluated by immunohistochemistry (IHC) and FISH. Definition of HER2 positivity was as follows; HER2-Pos as IHC 3+ or IHC 2+/FISH positive: HER2-L as IHC 2+/FISH negative or IHC 1+: Negative (HER2-Neg) as IHC 0+. NGS tests were also done. Results: Between 2005 and 2015, a total of 370 pts were analyzed; 60% were male, with a median age of 64 y/o. Fifteen pts (4%) with HER2-Pos, 21 (6%) with HER2-L, and 334 (90%) with HER2-Neg were identified. Proportion of left-sided primary tumor was similar among groups ranging from 72% to 78%. No difference was observed in terms of major clinicopathological characteristics. The proportion of co-altered RAS mutations in HER2-L was significantly higher than HER2-Pos ( p = 0.037) and similar to HER2-Neg (27% in HER2-Pos vs. 62% in HER2-L vs. 56% in HER2-Neg). As of median follow-up of 24.8 months, median overall survival (mOS) in HER2-L was significantly better than that in HER2- Pos ( p = 0.029, 18.2 months in HER2-Pos vs. 33.3 in HER2-L vs. 27.9 in HER2-Neg). In 58 pts harboring RAS wild-type who received an anti-EGFR monoclonal antibody therapy, median progression-free survival (mPFS) in HER2-L tended to be better than that in HER2- Pos, with 2.2 months in HER2-Pos, 7.8 in HER2-L, and 5.5 in HER2-Neg ( p = 0.099). Conclusions: Since HER2-L mCRC had the high prevalence of co-altered RAS mutations but showed a better prognosis and might benefit more from an anti-EGFR therapy than HES2-Pos, the HER2-L mCRC seems to have a different biological behavior from HER2-Pos in terms of molecular landscape and prognostic value on mCRC.