Improved survival among patients with malignant pleural mesotheliomas who develop immune-related adverse events on immunotherapy.

8556 Background: While immune checkpoint inhibitors (ICI) are a standard option for patients with malignant pleural mesotheliomas (MPM), there is limited data on the rate of immune related adverse events (irAEs) and effects on clinical outcomes. Methods: 61 patients with MPM who received ICI between January 2016 and October 2020 were assessed and followed through November 2020. irAEs (CTCAE v5.0) were noted along with the time from ICI start to irAE onset. Patients were grouped into irAE ever versus never. Clinicopathologic characteristics, prior treatments, and investigator assessed clinical benefit rate (CBR; partial response [PR] + stable disease [SD]) were compared by Fisher’s Exact and Mann-Whitney Tests. Overall survival (OS) and investigator assessed progression free survival (PFS) from ICI start were compared using Kaplan Meier. In consented patients (n = 56), next generation sequencing (MSK-IMPACT) was performed with HLA genotyping analysis by POLYSOLVER software and alleles for the three major MHC class I (HLA-A, -B, -C) genes were obtained from whole exome recapture. Results: Most patients were male (72%), smokers (55%), > 70 years old (median 72, range 34-90), and had epithelioid histology (67%). No patients had baseline autoimmune disease. The median line of prior systemic therapies to ICI start was 2 (range 1-5). 17 patients (28%) developed an irAE on therapy including 7 (11%) with grade 3 to 5 events (pneumonitis, myositis, pancreatitis, nephritis, encephalitis and adrenal insufficiency). The median time from ICI start to irAE was 2.5 months (range 2 days – 5.8 months). There was no association with dual ICI (n = 6) vs single agent (n = 11) and sooner onset (2.1 vs 4.0 months; p = 0.10) nor higher grade (median grade 2 vs 3; p = 0.31) of irAEs. 1 patient developed grade 5 pneumonitis with onset 2 days after initial dose of dual-ICI. Comparing patients with irAEs to those without, there was no difference in distribution of epithelioid histology (n = 10 vs 31; p = 0.54), median age (71 vs 72 years old; p = 0.43), nor prior thoracic radiation (n = 5 vs 11; p = 0.75).There was no difference in HLA type nor the fraction of HLA alleles of individual genes amongst the groups. Patients who had an irAE were on ICI longer than those that did not (median time on ICI 5.4 vs 0.9 months, respectively; p = 0.02). OS was higher in patients with irAEs compared to those without (21.1 vs 4.7 months; p = 0.003) as was PFS (6.8 vs 1.7 months; p = 0.01). There was a significant increase in the CBR between those that had an irAE (65%; 5 PR, 6 SD) and those that did not (27%; 2 PR, 10 SD; p = 0.006). Conclusions: 28% of patients with MPM who received ICIs developed an irAE and onset tended to be early in the course of treatment. There was no clear predictive clinicopathologic feature that correlated with the occurrence of irAE. There was a significant increase in OS, PFS, and CBR in patients that had an irAE compared to those that did not.

Grade G2 Rectal Neuroendocrine Tumor Is Much More Invasive Compared With G1 Tumor

BackgroundTo compare clinicopathologic feature of rectal neuroendocrine tumor (NET) grade G1 with G2 NET.MethodsSix hundred-one cases of rectal G1 and G2 NETs diagnosed in our center were analyzed.ResultsOf 601 cases of rectal NET, 515 cases were with grade G1 and 86 cases were with grade G2. Median tumor size was 0.7 cm. Compared with G1 NET, G2 tumors were with significantly larger tumor size (0.8 vs 2.2 cm, p < 0.001), less percentages of patients with tumors confined to submucosa (92.6 vs 42.8%, p < 0.001), more frequent presence of microvascular invasion (MVI) (3.6 vs 16.9%, p < 0.001) or peri-neural invasion (PNI) (2.0 vs 24.1%, p < 0.001). Incidence of lymph node and distant metastasis was 5.2 and 2.1% in G1 NET compared with 44.2 and 31.4% in G2 tumor, respectively (p < 0.001). For tumors sized 1–2 cm and confined to submucosa, incidence of lymph node metastasis was 6.1% for G1 NET compared with 21.1% for G2 NET. Status of MVI/PNI was predictive of lymph node metastasis for G2 tumor rather than G1 NET in this subgroup.ConclusionsRectal G2 NET was much more invasive with significantly elevated prevalence of lymph node metastasis compared with G1 tumor.

Exploration of the Tumor Mutational Burden as a Prognostic Biomarker and Related Hub Gene Identification in Prostate Cancer

To explore the signature function of the tumor mutational burden (TMB) and potential biomarkers in prostate cancer (PCa), transcriptome profiles, somatic mutation data, and clinicopathologic feature information were downloaded from The Cancer Genome Atlas (TCGA) database. R software package was used to generate a waterfall plot to summarize the specific mutation information and calculate the TMB value of PCa. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to select the hub genes related to the TMB from the ImmPort network to build a risk score (RS) model to evaluate prognostic values and plot Kaplan–Meier (K-M) curves to predict PCa patients survival. The results showed that PCa patients with a high TMB exhibited higher infiltration of CD8+ T cells and CD4+ T cells and better overall survival (OS) than those with a low TMB. The anti-Mullerian hormone (AMH), baculoviral IAP repeat-containing 5 (BIRC5), and opoid receptor kappa 1 (OPRK1) genes were three hub genes and their copy number variation (CNV) was relatively likely to affect the infiltration of immune cells. Moreover, PCa patients with low AMH or BIRC5 expression had a longer survival time and lower cancer recurrence, while elevated AMH or BIRC5 expression favored PCa progression. In contrast, PCa patients with low OPRK1 expression had poorer OS in the early stage of PCa and a higher recurrent rate than those with high expression. Taken together, these results suggest that the TMB may be a promising prognostic biomarker for PCa and that AMH, OPRK1, and BIRC5 are hub genes affecting the TMB; AMH, OPRK1, and BIRC5 could serve as potential immunotherapeutic targets for PCa treatment.

Basal-Like Subgroup is Associated with Younger Age, Increased Expression of Androgen Receptor, and Worse Prognosis, while Non-basal-like Subtype is Associated with Higher BMI in Triple-Negative Breast Cancer Patients

BACKGROUND: Triple-negative breast cancer (TNBC) represents a heterogenous disease which differ in characteristic, treatment response and prognosis. We aim to perform in-depth analysis on the clinicopathologic feature and the prognostic value of basal-like and non-basal-like TNBC patients in an Indonesian tertiary hospital.METHODS: We retrospectively included patients diagnosed with TNBC between 2014-2017. Clinical variables were collected from medical record. Expression of epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), p53 mutant and androgen receptor (AR) were examined by using immunohistochemistry (IHC).RESULTS: We included 67 subjects, 67.1% were basal-like and the remaining 32.9% were non-basal-like, with mean age of 51 years old, 59.7% subjects had BMI <25 and 40.3% subjects had BMI ≥25; 16.4%, 65.7%, and 17.9% subjects presented with early stage, locally advanced stage, and distant metastasis respectively; T<5 cm was found in 29.9% subjects, while 70.1% subjects had T≥5; 67.2% subjects presented with N-, while 32.8% subjects were N+. The most common histological type was infiltrating ductal (82% of subjects). P53 mutant and AR expressions were positive in 44.8% and 15% subjects, respectively. Basal-like subtype presented with younger age at and had higher expression of AR, while non-basal-like subtype is associated with BMI ≥25 (p<0.05). Basal-like subjects had shorter overall survival (23.9 months (95% CI: 21.9-25.9) vs. 26.1 months (95% CI: 23-29.2).CONCLUSION: Basal-like subtype is associated with worse prognosis, younger age at diagnosis and increased expression of AR, while non-basal-like subtype is associated with higher BMI in Indonesian TNBC.KEYWORDS: TNBC, subtype; basal-like, young age, Indonesia

Potential risks in sentinel lymph node biopsy for cervical cancer: a single-institution pilot study

Background：Sentinel lymph node (SLN) biopsy is an attractive technique that widely performed in many oncological surgeries. However, the potential risks in SLN biopsy for cervical cancer remains largely unclear. Methods：Seventy-five patients with histologically confirmed cervical cancer were enrolled between May 2014 and June 2016. SLN biopsies were performed followed by pelvic lymphadenectomies and all resected nodes were labeled according to their anatomic areas. Only bilateral detections of SLNs were considered as successful. Patients’ clinicopathologic feature, performance of SLN detection, and distributions of lymph node metastases were analyzed. Results: Of the 75 enrolled patients, at least one SLN was detected in 69 (92.0%), including 33 in bilateral and 36 in unilateral. SLNs were most detected in obturator area (52 of 69 patients, 75.4%) and 26 (37.7%) patients presented SLNs in more than one area of hemipelvis. Lymphovascular invasion was found to be the only factor that adversely influenced SLN detection, while the tumor diameter, growth type, histological grade, deep stromal invasion and neoadjuvant chemotherapy showed no significant impacts. Patients with lymphovascular invasion showed significantly higher rate to have unsuccessful detection (90.9% versus 41.5%, P<0.001) and lymph node metastasis (40.9% versus 3.8%, P<0.001) compared with those without. Nodal metastases were confirmed in 11 patients, of whom 9 (81.8%) had lymphovascular invasion and 7 (63.6%) had non-SLN metastasis. The most frequently involved SLNs were obturator nodes (9/11, 81.8%). In addition, the parametrial nodes also has high rate to be positive (4/11, 36.4%), although they were relatively less identified as SLNs. Besides, 3 patients showed metastases in the laterals without SLN detected.Conclusions: In cervical cancer, lymphovascular invasion is a significant factor for unsuccessful SLN detection. The risk of having undetected metastasis is high when SLN is positive, therefore further lymphadenectomy may be necessary for these patients.

Comparing clinicopathologic feature and treatment outcome of patients who underwent surgical resection or liver transplant for nonalcoholic fatty liver disease (NAFLD)-related and non-NAFLD related hepatocellular carcinoma (HCC).

e16675 Background: NAFLD associated HCC is rapidly increasing in frequency worldwide. In this study, we evaluated potential differences in clinical characteristics and outcomes of patients who underwent surgery or liver transplant for NAFLD-associated HCC compared to HCC from other etiologies. Methods: Demographic, clinicopathological features and outcomes of patients with HCC who underwent liver resection or liver transplant at Massachusetts General Hospital and Brigham and Women’s Hospital were collected (January 2004 - April 2018). Of 713 patients screened, 481were eligible: 260 underwent resection [NAFLD (n = 61), viral (n = 150), cryptogenic (CC) (n = 49)]. 221 underwent transplant [(NAFLD (n = 14), viral (n = 201), CC (n = 6)]. Results: In the Resected cohort, NAFLD patients presented with median age of (71.5 years) compared with Viral (63.4) and Cryptogenic (68.4). NAFLD patients had significantly higher Body Mass Index (BMI) > 28.8 39(66%) p = < 0.001, while patients with cryptogenic HCC presented with large tumor size (>5cm) 37(75%) p = 0.001. In multivariate analysis, tumor size 5cm (HR1.78,p = 0.002), R1 or R2 resection (HR 2.48, p = < 0.001and 2.8,p = 0.007), low platelet count (HR 2.8,p = 0.002) and diabetes (HR 1.5,p = 0.025) were poor prognostic factors in resection cohort. Median overall survival (OS) was not significantly different between NAFLD, Cryptogenic and Viral (47.2, 69.7 and 69.0 months, p = 0.18) etiologies, respectively. In the Transplant cohort, NAFLD patients had a median age of 65.5 and cryptogenic, viral (61.3 and 58.5 years) respectively. NAFLD and Cryptogenic HCC patients compared with viral HCC patients had low AFP median 3.7, 3.9 and 7.5 ng/mL(p = 0.012) respectively. In multivariate analysis patients with perineural invasion (HR 20.7,p = 0.009), disease recurrence (HR 2.5,p = 0.001) and high AFP (HR 2.1,p = 0.001) were at higher risk of death among transplant patients. No significant difference in median OS was seen between NAFLD, cryptogenic and viral (69.1,92.3 and 88.0 months, p = 0.38). Conclusions: NAFLD patients had higher BMI and had a lower AFP than viral and CC. NAFLD had similar median OS following resection and transplant when compared to those with Viral and CC.

Potential Risks in Sentinel Lymph Node Biopsy for Cervical Cancer: A Single-Institution Pilot Study

Background: Sentinel lymph node (SLN) biopsy is an attractive technique that widely performed in many oncological surgeries. However, the potential risks in SLN biopsy for cervical cancer remains largely unclear. Methods: Seventy-five patients with histologically confirmed cervical cancer were enrolled between May 2014 and June 2016. SLN biopsies were performed followed by pelvic lymphadenectomies and all resected nodes were labeled according to their anatomic areas. Only bilateral detections of SLNs were considered as successful. Patients’ clinicopathologic feature, performance of SLN detection, and distributions of lymph node metastases were analyzed. Results: Of the 75 enrolled patients, at least one SLN was detected in 69 (92.0%), including 33 in bilateral and 36 in unilateral. SLNs were most detected in obturator area (52 of 69 patients, 75.4%) and 26 (37.7%) patients presented SLNs in more than one area of hemipelvis. Lymphovascular invasion was found to be the only factor that adversely influenced SLN detection, while the tumor diameter, growth type, histological grade, deep stromal invasion and neoadjuvant chemotherapy showed no significant impacts. Patients with lymphovascular invasion showed significantly higher rate to have unsuccessful detection (90.9% versus 41.5%, P<0.001) and lymph node metastasis (40.9% versus 3.8%, P<0.001) compared with those without. Nodal metastases were confirmed in 11 patients, of whom 9 (81.8%) had lymphovascular invasion and 7 (63.6%) had non-SLN metastasis. The most frequently involved SLNs were obturator nodes (9/11, 81.8%). In addition, the parametrial nodes also has high rate to be positive (4/11, 36.4%), although they were relatively less identified as SLNs. Besides, 3 patients showed metastases in the laterals without SLN detected. Conclusions: In cervical cancer, lymphovascular invasion is a significant factor for unsuccessful SLN detection, which harbors the risk of omitting nodal metastasis. The risk of having undetected metastasis is high when SLN is positive, therefore further lymphadenectomy may be necessary for these patients.