Difference In Median Survival Research Articles

An iodine-125 seed strand combined with a metal stent versus a metal stent alone for obstructive jaundice caused by pancreatic ductal adenocarcinoma

PurposeThe purpose of this study was to assess the efficacy of an iodine-125 (125I) seed strand combined with a metal stent compared with a metal stent for treatment of obstructive jaundice caused by pancreatic ductal adenocarcinoma (PDAC). Methods and MaterialsA retrospective analysis was carried out of patients who were referred to Shanghai Zhongshan Hospital of Fudan University with a diagnosis of PDAC between January 1, 2010 and January 31, 2019. A total of 110 consecutive patients with obstructive jaundice caused by PDAC were divided into the iodine-125 seed strand combined with a metal stent group (Group A = 48) and the metal stent group (Group B = 62). The primary outcome was stent obstruction–free survival time, and secondary outcomes were overall survival and complications. ResultsThe median stent obstruction–free survival time was 133.0 (95% confidence interval (CI): 166.093–149.907) days, and the median overall survival was 212.0 (95% CI: 187.183–236.817) days in all patients. Median stent obstruction–free survival time was 175 days (95% CI 103.165–246.835 days) in Group A versus 120 days (95% CI 87.475–152.525 days) in Group B (p = 0.035). A lower Eastern Cooperative Oncology Group (ECOG) score (p = 0. 000) and iodine-125 seed strand combined with metal stent implantation (p = 0.008) were associated with a longer stent obstruction–free survival time. Obstruction length (p = 0.083), ECOG score (p = 0.000), and iodine-125 seeds (p = 0.037) might have potential impact on stent obstruction–free survival time and were included for multivariable analysis using the Cox proportional hazards model. Stent restenosis was observed in 18.8% (9/48) of patients in Group A and 54.8% (34/62) in Group B, respectively. There was no significant difference in median survival between Group A and Group B (p = 0.409). The median survival in Group A was 209 days (95% CI 150.750–267.250) and 202 days (95% CI 190.624–233.376) in Group B. The median survival of patients with a lower ECOG score was better than that of patients with a higher ECOG score (267 days vs 132 days, p = 0.000). The Grade 3 or 4 complications occurred in 4 (8.3%) of the 48 patients in Group A (one case of hemobilia, one case of liver abscess, two cases of choleperitonitis) and in 5 (8.1%) of the 62 patients in Group B (one case of hemobilia, two cases of liver abscess, two cases of choleperitonitis) (p = 0.972). ConclusionsImplantation of an iodine-125 seed strand combined with a metal stent provides longer obstruction-free survival time compared with a metal stent in patients with obstructive jaundice caused by PDAC. It seems reasonable to choose an iodine-125 seed strand combined with a metal stent as a treatment for these patients.

Outcomes of 350 Robotic-assisted Esophagectomies at a High-volume Cancer Center: A Contemporary Propensity-score Matched Analysis.

To evaluate perioperative and oncologic outcomes in our RAMIE cohort and compare outcomes with contemporary OE controls. RAMIE has emerged as an alternative to traditional open or laparoscopic approaches. Described in all esophagectomy techniques, rapid adoption has been attributed to both enhanced visualization and technical dexterity. We retrospectively reviewed patients who underwent RAMIE for malignancy. Patient characteristics, perioperative outcomes, and survival were evaluated. For perioperative and oncologic outcome comparison, contemporary OE controls were propensity-score matched from NSQIP and NCDB databases. We identified 350 patients who underwent RAMIE between 2010 and 2019. Median body mass index was 27.4, 32% demonstrated a Charlson Comorbidity Index >4. Nodal disease was identified in 50% of patients and 74% received neoadjuvant chemoradiotherapy. Mean operative time and blood loss were 425 minutes and 232 mL, respectively. Anastomotic leak occurred in 16% of patients, 2% required reoperation. Median LOS was 9 days, and 30-day mortality was 3%. A median of 21 nodes were dissected with 96% achieving an R0 resection. Median survival was 67.4 months. 222 RAMIE were matched 1:1 to the NSQIP OE control. RAMIE demonstrated decreased LOS (9 vs 10 days, P = 0.010) and reoperative rates (2.3 vs 12.2%, P = 0.001), longer operative time (427 vs 311 minutes, P = 0.001), and increased rate of pulmonary embolism (5.4% vs 0.9%, P = 0.007) in comparison to NSQIP cohort. There was no difference in leak rate or mortality. Three hundred forty-three RAMIE were matched to OE cohort from NCDB with no difference in median overall survival (63 vs 53 months; P = 0.130). In this largest reported institutional series, we demonstrate that RAMIE can be performed safely with excellent oncologic outcomes and decreased hospital stay when compared to the open approach.

Gilteritinib Remains Clinically Active in Relapsed/Refractory FLT3 Mutated AML Previously Treated with FLT3 inhibitors

Gilteritinib Remains Clinically Active in Relapsed/Refractory FLT3 Mutated AML Previously Treated with FLT3 inhibitors

What Multiple Myeloma With t(11;14) Should Be Classified Into in Novel Agent Era: Standard or Intermediate Risk?

ObjectiveTo investigate the prognostic value of t(11;14) for de novo multiple myeloma (MM) patients in novel agent era.MethodsA total of 455 patients with fluorescence in situ hybridization (FISH), before treatments from three hospitals in China, were included in the study. All patients received autologous stem cell transplantation (ASCT) after induction therapy as consolidation. High risk (HR) cytogenetics were defined as t(4;14), t(14;16), and/or del 17p.ResultsA total of 152 patients were in the HR group. Of patients without HR cytogenetics, 55 were in the t(11;14) group, and 248 were in the standard risk (SR) group without t(11;14). Gain in 1q21 was observed in 38.9% patients with t(11;14). There were no differences in median progression free survival (PFS) and overall survival (OS), respectively, between patients in the t(11;14) group and those in the SR group. Patients in the t(11;14) group had the longer median PFS and OS, respectively, compared with those in the HR group. Regardless of coexisting with 1q21 gain or not, patients in the t(11;14) group still had similar median PFS and OS compared to those in the SR group. Finally, multivariate analysis indicated that including 1q21 gain and bone marrow plasma cell with CD20 expression, no variables were found to predict the outcome of the t(11;14) group in our cohort.ConclusionsThese results confirm that outcomes of t(11;14) MM are similar to standard risk patients when they receive novel agent induction therapy consolidated by ASCT. Gain of 1q21 coexists with t(11;14) frequently. In addition, both bone marrow plasma cell with CD20 expression and 1q21 gain have no impact on median PFS or OS for patients with t(11;14).

Management of primary and metastatic malignant small bowel obstruction, operate or palliate. A systematic review.

The management of patients presenting with malignant small bowel obstruction is a challenging paradigm. The aim of this systematic review was to examine different management strategies in these complex patients. The primary outcomes evaluated were the type of intervention, 30-day morbidity and mortality and overall survival rates. A systematic literature review of EMBase, Medline, PubMed and the Cochrane Library was performed using Preferred Reporting Items for Systematic reviews and Meta-Analyses for studies reporting on conservative and operative management of malignant small bowel obstruction. Fifteen studies (n = 882 patients) reporting on outcomes for malignant small bowel obstruction were analysed. Outcomes measured were primarily survival and relief of obstructive symptoms. The median age ranged from 52 to 66 years. The most common cause of malignant small bowel obstruction was gynaecological in nature (56%), followed by colorectal (19%). Four hundred and eighty-six patients underwent primary surgical management and the remaining 396 patients were assigned to non-surgical intervention. Median overall survival in the operative studies ranged from 2.5 to 7.4 months compared with 0.9 to 1.9 months (P < 0.05). The 30-day mortality ranged from 13% to 28% in those who underwent surgical interventions versus 2% to 61% in the non-surgical group (P = 0.09). No significant difference in median survival in gastrointestinal (GI) and gynaecological malignancies was observed (4.3 versus 5.0 months, P = 0.12). Morbidity ranged from 21% to 85% in the surgical group and 12% to 29% in the percutaneous groups (P < 0.05). Surgical intervention in malignant small bowel obstruction is associated with significant morbidity, although it may improve survival in selected patients with gynaecological and colorectal malignancy. It is imperative that realistic goals and expectations are discussed with patients preoperatively.

BCR-ABL1–Negative Chronic Myeloproliferative Neoplasms and Pulmonary Hypertension: A Prospective Long-Term Follow-up Study of the Impact of Pulmonary Hypertension on Survival

PurposeTo assess the prevalence of PHT in patients with BCR-ABL1–negative CMPN and to evaluate impact of PHT on survival during long-term follow-up. Patients and MethodsA total of 122 patients with BCR-ABL1–negative CMPN underwent transthoracic echocardiographic (TTE) evaluation at the beginning of study. Patients undergoing PHT on TTE examination were also evaluated by a pulmonologist. Patients were divided into 3 groups. Group A comprised patients with CMPN-related PHT; group B, patients with no PHT; and group C, patients with PHT due to secondary causes. Patients were evaluated again every 3 to 6 months. ResultsPHT was detected in 33 (27%) of 122 patients. Eight (6.5%) had CMPN-related PHT and the remaining 25 (20.5%) had non–CMPN-related PHT. Positivity for JAK2 V617F mutation in the study population was 72.9%. Groups were similar with respect to hematologic parameters and gender. Follow-up times were as follows: median (range) time from diagnosis to TTE and study end were 34 (1-158) months and 107 (16-251) months, respectively, and from TTE to study end was 88 (7-110) months. No significant differences found among the groups in terms of median time from diagnosis to TTE, follow-up, and overall survival. ConclusionBCR-ABL1–negative CMPN patients had a lower prevalence of PHT compared to earlier studies. There was no statistically significant difference in median overall survival between patients with or without PHT. This may be because patients with PHT were asymptomatic and PHT was mild. The impact of PHT on survival was negligible.

Comparison of hyperthermic intraperitoneal chemotherapy regimens for treatment of peritoneal-metastasized colorectal cancer.

BACKGROUNDCytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improves patient survival in colorectal cancer (CRC) with peritoneal carcinomatosis (PC). Commonly used cytotoxic agents include mitomycin C (MMC) and oxaliplatin. Studies have reported varying results, and the evidence for the choice of the HIPEC agent and uniform procedure protocols is limited.AIMTo evaluate therapeutic benefits and complications of CRS + MMC vs oxaliplatin HIPEC in patients with peritoneal metastasized CRC as well as prognostic factors.METHODSOne hundred and two consecutive patients who had undergone CRS and HIPEC for CRC PC between 2007 and 2019 at the Medical Center of the University Freiburg regarding interdisciplinary cancer conference decision were retrospectively analysed. Oxaliplatin and MMC were used in 68 and 34 patients, respectively. Each patient’s demographics and tumour characteristics, operative details, postoperative complications and survival were noted. Complications were stratified and graded using Clavien/Dindo analysis. Prognostic outcome factors were identified using univariate and multivariate analysis of survival.RESULTSThe two groups did not differ significantly regarding baseline characteristics. We found no difference in median overall survival between MMC and oxaliplatin HIPEC. Regarding postoperative complications, patients treated with oxaliplatin HIPEC suffered increased complications (66.2% vs 35.3%; P = 0.003), particularly intestinal atony, intraabdominal infections and urinary tract infection, and had a prolonged intensive care unit stay compared to the MMC group (7.2 d vs 4.4 d; P = 0.035). Regarding univariate analysis of survival, we found primary tumour factors, nodal positivity and resection margins to be of prognostic value as well as peritoneal cancer index (PCI)-score and the completeness of cytoreduction regarding peritoneal carcinomatosis. Multivariate analysis of survival confirmed primary distant metastasis and primary tumour resection status to have a significant impact on survival and likewise peritoneal cancer index-scoring regarding peritoneal carcinomatosis.CONCLUSIONIn this single-institution retrospective review of patients undergoing CRS with either oxaliplatin or MMC HIPEC, overall survival was not different, though oxaliplatin was associated with a higher postoperative complication rate, indicating treatment favourably with MMC. Further studies comparing HIPEC regimens would improve evidence-based decision-making.

Abstract 5080: Prognostic immune subtypes in glioblastoma

Abstract Variations in the tumor immune microenvironment between Glioblastoma (GBM) patients complicates development and testing of immunotherapies. We used publicly available single cell RNA sequencing data of GBM patients to extract pan immune-specific genes in GBM. Interrogating bulk GBM sequencing or microarray data with pan immune-specific genes should allow examination of the immune component. We used these genes to investigate subtypes of GBM immune microenvironments. Consensus clustering using these genes on GBM TCGA RNAseq data gave 4 distinct subtypes while 12% of tumors were not assigned to any of those subtypes. Immune subtypes had distinct clinical outcomes. Differences in median survival (16.6 vs 5.8 months; longest vs. shortest survival; p &amp;lt; 1e-05 Logrank, Wald and Likelihood ratio tests) suggests the immune microenvironment significantly impacts clinical course. Cox univariate analysis indicates age had no contribution to risk (HR = 1.034; 95% confidence interval 1.017-1.052). We propose that immune-subtyping of GBM with pan immune-specific genes will lead to biomarkers that predict immunotherapeutic response. It will also help to identify molecular pathways and targets that suppress the immune anti-tumor response. Citation Format: Anna Joy, Xishuang Dong, Seungchan Kim. Prognostic immune subtypes in glioblastoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5080.

International real-world study of DLL3 expression in patients with small cell lung cancer

ObjectivesExpression of the Notch-family ligand delta-like protein 3 (DLL3), a potential therapeutic target in small cell lung cancer (SCLC), has not been assessed in the real-world setting. To identify the real-world utility of DLL3 as an SCLC therapeutic target, we performed the largest retrospective international noninterventional study to date to evaluate DLL3 prevalence in SCLC patients. Materials and MethodsDLL3 expression was assessed using immunohistochemistry in archived histological and cytological specimens (independent and paired) and correlated to patient demographics, clinical disease characteristics, and survival. The primary endpoint was the proportion of patients with DLL3 expression in ≥25 % of tumor cells. DLL3 expression concordance was assessed in paired specimens. ResultsIndependent tumor specimens were collected from 1073 patients. The mean age at biopsy was 66 years (SD, 10); 682 (64 %) patients were male. Paired specimens were collected from 36 patients. The mean age at biopsy was 62 years (SD, 11); 16 (44 %) patients were male. Most patients had ECOG performance status of 0–1, were smokers/ex-smokers, and received ≥1 prior therapy. Positive DLL3 expression (defined as ≥25 % of tumor cells) was identified in 895/1050 (85 %) patients with 1 specimen and evaluable DLL3 expression; 719/1050 (68 %) patients had high DLL3 expression (defined as ≥75 % of tumor cells). DLL3 expression concordance was 88 % between paired specimens (n = 17; Cohen’s kappa P value, .9412). There was no significant difference in median overall survival from SCLC diagnosis for evaluable patients with nonmissing data based on DLL3 expression (negative DLL3 expression [n = 139], 9.5 months; positive DLL3 expression [n = 747], 9.5 months; all evaluable patients [n = 893, 9.5 months). ConclusionThese real-world epidemiologic findings indicate that DLL3 is robustly expressed across SCLC disease stages and remains stable despite treatment, consistent with available clinical trial data. There was no prognostic role for DLL3 observed in this study for overall survival.

Life expectancy with glioblastoma at GMC, Bhopal

Life expectancy with glioblastoma at GMC, Bhopal - IJN- Print ISSN No: - 2581-8236 Online ISSN No:- 2581-916X Article DOI No:- 10.18231/j.ijn.2020.026, IP Indian Journal of Neurosciences-IP Indian J Neurosci

Germline mutation rates in young adults\xa0predict longevity and reproductive lifespan

Ageing may be due to mutation accumulation across the lifespan, leading to tissue dysfunction, disease, and death. We tested whether germline autosomal mutation rates in young adults predict their remaining survival, and, for women, their reproductive lifespans. Age-adjusted mutation rates (AAMRs) in 61 women and 61 men from the Utah CEPH (Centre d’Etude du Polymorphisme Humain) families were determined. Age at death, cause of death, all-site cancer incidence, and reproductive histories were provided by the Utah Population Database, Utah Cancer Registry, and Utah Genetic Reference Project. Higher AAMRs were significantly associated with higher all-cause mortality in both sexes combined. Subjects in the top quartile of AAMRs experienced more than twice the mortality of bottom quartile subjects (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.21–3.56; p = 0.008; median survival difference = 4.7 years). Fertility analyses were restricted to women whose age at last birth (ALB) was ≥ 30 years, the age when fertility begins to decline. Women with higher AAMRs had significantly fewer live births and a younger ALB. Adult germline mutation accumulation rates are established in adolescence, and later menarche in women is associated with delayed mutation accumulation. We conclude that germline mutation rates in healthy young adults may provide a measure of both reproductive and systemic ageing. Puberty may induce the establishment of adult mutation accumulation rates, just when DNA repair systems begin their lifelong decline.

Systemic therapy without radiation may be appropriate as neoadjuvant therapy for localized pancreas cancer.

The utility of neoadjuvant treatment for resectable pancreas cancer is yet to be determined, but has commonly included chemoradiation. We evaluated outcomes in patients with radiographically resectable pancreatic adenocarcinoma treated with neoadjuvant chemotherapy without chemoradiation. A retrospective review of patients in our institutional pancreatic cancer registry was performed, which identified 36 patients who received neoadjuvant chemotherapy alone for resectable pancreatic adenocarcinoma between 2012 and 2016. Median age at diagnosis was 66.3 years. Chemotherapy regimens included gemcitabine (n=17), gemcitabine/nab-paclitaxel (n=8), or 5-FU/leucovorin/irinotecan/oxaliplatin (FOLFIRINOX) (n=11). Surgical resection was performed in 69% of patients (n=25), with an R0 resection rate of 92% (n=23 patients). During chemotherapy, distant disease became apparent in 19% of patients (n=7), while no patients had evidence of local progression. Resection rates were similar between chemotherapy regimens (single agent =59%, multiple agent =79%). Median overall survival for all patients who received neoadjuvant chemotherapy was 30.3 and 34.4 months for those who underwent surgical resection. There was no difference in median survival for patients treated with gemcitabine (31.3 months) or multi-agent chemotherapy (29.7 months). A short course of neoadjuvant chemotherapy without chemoradiation may improve patient selection prior to surgical resection for pancreas cancer. Further, local disease progression did not limit surgical resection in this small series.

Big Data-Based Identification of Multi-Gene Prognostic Signatures in Liver Cancer.

Simultaneous identification of multiple single genes and multi-gene prognostic signatures with higher efficacy in liver cancer has rarely been reported. Here, 1,173 genes potentially related to the liver cancer prognosis were mined with Coremine, and the gene expression and survival data in 370 samples for overall survival (OS) and 319 samples for disease-free survival (DFS) were retrieved from The Cancer Genome Atlas. Numerous survival analyses results revealed that 39 genes and 28 genes significantly associated with DFS and OS in liver cancer, including 18 and 12 novel genes that have not been systematically reported in relation to the liver cancer prognosis, respectively. Next, totally 9,139 three-gene combinations (including 816 constructed by 18 novel genes) for predicting DFS and 3,276 three-gene combinations (including 220 constructed by 12 novel genes) for predicting OS were constructed based on the above genes, and the top 15 of these four parts three-gene combinations were selected and shown. Moreover, a huge difference between high and low expression group of these three-gene combination was detected, with median survival difference of DFS up to 65.01 months, and of OS up to 83.57 months. The high or low expression group of these three-gene combinations can predict the longest prognosis of DFS and OS is 71.91 months and 102.66 months, and the shortest is 6.24 months and 13.96 months. Quantitative real-time polymerase chain reaction and immunohistochemistry reconfirmed that three genes F2, GOT2, and TRPV1 contained in one of the above combinations, are significantly dysregulated in liver cancer tissues, low expression of F2, GOT2, and TRPV1 is associated with poor prognosis in liver cancer. Overall, we discovered a few novel single genes and multi-gene combinations biomarkers that are closely related to the long-term prognosis of liver cancer, and they can be potential therapeutic targets for liver cancer.

Evaluation of the correlation between antibiotic use and survival in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs).

6509 Background: Recent evidence suggests that treatment with systemic antibiotics (Abx) disrupts the intestinal microbiome and may be associated with decreased survival for patients receiving treatment with ICIs for advanced cancers, including R/M HNSCC. However, a potential confounder is that Abx use identifies a subgroup of patients with a worse prognosis. The FDA examined the association between Abx use and survival for ICIs and other drugs used for the treatment of patients with R/M HNSCC. Methods: Data submitted to the FDA from three randomized controlled trials with ICI as a single agent or with chemotherapy (ICI group) compared to chemotherapy and/or cetuximab (Control group) were pooled. The association between systemic Abx use within 30 days of initiating anticancer therapy and survival for the ICI and Control groups was evaluated using Kaplan-Meier (KM) estimates and compared using Cox proportional hazards regression models, controlling for ECOG performance status, line of therapy, HPV status, PD-L1 expression, and other important prognostic factors. Results: In the ICI and Control groups, 36% and 46% of patients received Abx, respectively. For the ICI group, the difference in KM-estimated median overall survival (OS) was 5.6 months based on receipt of Abx (hazard ratio [HR] 1.70). Abx had no impact on OS for the Control group. Similar trends were observed for progression-free survival (PFS). Conclusions: In this exploratory analysis, systemic Abx within 30 days of initiating treatment for R/M HNSCC was associated with decreased survival for patients treated with ICIs compared with patients who did not receive Abx. Use of Abx had no apparent difference in survival in the control group. Further examination of the association between Abx use and clinical outcomes for patients with R/M HNSCC treated with ICIs is needed. [Table: see text]

Donafenib versus sorafenib as first-line therapy in advanced hepatocellular carcinoma: An open-label, randomized, multicenter phase II/III trial.

4506 Background: Sorafenib is still the standard first-line therapy for advanced hepatocellular carcinoma (HCC). Donafenib, a novel multikinase inhibitor, showed potential benefits in a previous phase Ib study in HCC. Methods: In this open-label, randomized phase II/III trial (ZGDH3), patients with unresectable or metastatic HCC, a Child-Pugh liver function score ≤ 7, and no prior systemic therapy were enrolled from 37 sites across China and randomized (1:1) to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression. The primary endpoint was overall survival (OS). Efficacy analysis was primarily based on the full analysis set (FAS). Results: Between March 2016 and April 2018, 668 patients were randomized (donafenib, 334; sorafenib, 334) and included in the intention-to-treat (ITT) set, of whom 659 were analysed by FAS (328 vs 331). Donafenib was associated with a significantly longer median OS than sorafenib in both FAS (12.1 months vs 10.3 months, hazard ratio 0.831, 95% confidence interval 0.699–0.988, p = 0.0363) and ITT (12.0 months vs 10.1 months, 0.839, 0.706–0.996, p = 0.0446). There were no significant differences in median progression-free survival (3.7 months vs 3.6 months, p = 0.2824), objective response rate (4.6% vs 2.7%, p = 0.2448), and disease control rate (30.8% vs 28.7%, p = 0.5532). Grade 3 or worse adverse events (AEs) occurred in 191 (57.4%) and 224 (67.5%) patients ( p = 0.0082), respectively, and AEs of special interest and those leading to treatment interruption occurred in 287 (86.2%) vs 309 (93.1%, p = 0.0049) and 101 (30.3%) vs 141 (42.5%, p = 0.0013). A numerically lower number of patients reported serious AEs (55 [16.5%] vs 67 [20.2%], p = 0.2307) with donafenib. Common AEs with donafenib included hand-foot skin reaction (50.5%), aspartate aminotransferase increased (40.5%), blood bilirubin increased (39.0%), platelet count decreased (37.8%), and diarrhea (36.6%). Conclusions: Donafenib significantly improves OS over sorafenib with favourable safety and tolerability. Donafenib is a promising superior first-line therapy for advanced HCC. Funding: Zelgen. Clinical trial information: NCT02645981 .

Total mesorectal excision compared to local excision in locally advanced rectal cancer achieving complete pathological response with neoadjuvant therapy: A National Cancer Database Analysis.

4107 Background: Total mesorectal excision (TME) is the standard surgical intervention for patients with locally advanced rectal cancer (LARC) regardless of response to neoadjuvant therapy. In this study, we perform a comprehensive review of the National Cancer Database (NCDP) to compare the clinical and surgical outcomes of TME to local excision (LE) in patients with LARC. Methods: NCDP was systematically researched to abstract all patients with stage II and III rectal adenocarcinoma between the years 2004 and 2015. We subsequently excluded all the patients who did not achieve complete pathological response (pT0) after neoadjuvant therapy. The patients were then divided into two groups; those who underwent TME and those who underwent LE. Data were analyzed using SPSS v. 26.0, SAS v. 9.4. Results: A total of 4,705 were included in the study; 4,589 in the TME group and 116 in the LE group. Baseline characteristics were similar between the groups except for age. A total of 81(1.8%) of patients in the TME group and 8(6.9%) of patients in the LE group did not receive radiation (p=0.006) and 19(0.4%) of patients the TME group and 4(3.4%) of patients in the LE group did not receive chemotherapy. There was no difference in median overall survival between TME and LE groups. The median length of hospital stay was remarkably shorter in the LE group compared to the TME group (1 day vs 6 days, p&lt;0.0001). The rate of 30-day and 90-day postoperative mortality were similar between the two groups (p-value=0.334 and 0.06, respectively). In the LE group, 4 (3.4%) of patients were readmitted within 30 days of the resection compared to 374 (8.5%) in the TME group but was not a statistically significant difference (p=0.059). Conclusions: In this study, TME and LE had similar overall survival and time to 25% mortality in patients with LARC who achieved complete pathological response after neoadjuvant therapy. Also, LE had a shorter hospital stay compared to the TME group. This study is limited by its retrospective nature, however these interesting observations warrant further investigation in randomized clinical trials. [Table: see text]

Efficacy and Safety of Sorafenib in Unresectable Hepatocellular Carcinoma with Bile Duct Invasion

Introduction: Because the frequency of bile duct invasion in hepatocellular carcinoma (HCC) patients is very rare, there is limited clinical evidence to demonstrate the outcomes of systemic therapy in HCC with bile duct invasion. Objective: Our aim was to clarify the efficacy and safety of sorafenib treatment in patients with unresectable advanced HCC with bile duct invasion. Methods: One hundred and seventy-five patients with advanced HCC were enrolled in this study. We retrospectively compared the outcomes of sorafenib between patients without bile duct invasion [B (−) group, n = 165] and those with bile duct invasion [B (+) group, n = 10]. Results: There were no significant differences in the confirmed objective response rate (ORR) and the confirmed disease control (DC) rate between the B (−) and the B (+) groups (13.9 vs. 20.0%, p = 0.637 for ORR; 47.2 vs. 70.0%, p = 0.202 for DC rate, respectively). There were no significant differences in median overall survival (OS) and time to progression (TTP) between the B (−) group and the B (+) group (14.8 vs. 14.1 months, p = 0.780 for OS; 3.4 vs. 5.7 months, p = 0.277 for TTP, respectively). Post-treatment factors associated with good OS were changes in albumin-bilirubin score (0–6 weeks) of <0.25, and antitumor response at 6 weeks of DC. Though 5 of 10 patients (50%) in the B (+) group had bile duct complications, such as obstructive jaundice and biliary bleeding, these 5 patients were able to recover from biliary troubles by careful and vigorous management with biliary endoscopic intervention, and were able to continue sorafenib therapy safely. Conclusions: Our present results suggest that sorafenib might have potential therapeutic efficacy and safety in advanced HCC patients with bile duct invasion. In case of biliary tract troubles before and during sorafenib treatment, early biliary management may be important to continue sorafenib therapy safely. Further studies are needed to confirm the outcomes of sorafenib in advanced HCC patients with bile duct invasion.

Machine learning guided adjuvant treatment of head and neck cancer.

6567 Background: A combined analysis of the EORTC 22931 and RTOG 95-01 trials confirmed that patients (pts) with head and neck squamous cell carcinoma (HNSCC) and positive margins or extracapsular extension (ECE) benefit from adjuvant chemoradiotherapy (CRT), but the best treatment of pts with other risk factors is unclear. We hypothesized that deep learning models could identify the margin/ECE negative pts who benefit from CRT. Methods: We abstracted pts from the NCDB diagnosed from 2004-2016 with resected HNSCC who received radiotherapy (RT). We reserved 20% of pts for validation and used the remaining 80% for feature selection and model training. Features were chosen based on independent significance in a Cox proportional hazards model, and included demographics, tumor stage, site, grade, RT dose, and receipt of chemotherapy. HPV status was included, and imputed when unknown. We generated survival predictions with DeepSurv (DS), random survival forest (RSF), and neural network multitask (NNM) models. We consider CRT to be recommended by a model if predicted survival is longer with CRT than RT. We calculated the median overall survival (mOS) difference and hazard ratio (HR) for receipt of treatment in line with model recommendations. This was repeated with inverse probability of treatment weighting (IPTW) to account for confounding. As a comparator, we used the intermediate risk factors in the EORTC (T3-4 except T3N0 larynx, N2-3, LVI, deep nodes with oral / oropharynx cancer) and RTOG (2 involved nodes) trials as decision rules. Results: 36,831 pts from the NCDB met the inclusion criteria. 92% had T3-4 or node positive disease, and 40% received CRT. RTOG, EORTC, DS, NNM, and RSF models recommend CRT for 32%, 74%, 63%, 61%, and 35% of pts. The concordance index in the validation set was 0.696, 0.692, and 0.699 for DS, NNM, and RSF. Treatment according to model recommendations in the validation cohort was associated with a mOS benefit of 18.4 months (7.6 to 29.3, 95% CI) for DS, 20.5 months (8.8 to 32.2, 95% CI) for NNM, and 5.8 months (-6.6 to 18.3, 95% CI) for RSF. Similar results were seen with IPTW. Conclusions: Machine learning models can predict benefit from CRT in margin/ECE negative pts, and outperform treatment according to EORTC or RTOG inclusion criteria in this cohort. External validation of these models is warranted. [Table: see text]

Retrospective clinical trial experimentally validates glioblastoma genome-wide pattern of DNA copy-number alterations predictor of survival.

Modeling of genomic profiles from the Cancer Genome Atlas (TCGA) by using recently developed mathematical frameworks has associated a genome-wide pattern of DNA copy-number alterations with a shorter, roughly one-year, median survival time in glioblastoma (GBM) patients. Here, to experimentally test this relationship, we whole-genome sequenced DNA from tumor samples of patients. We show that the patients represent the U.S. adult GBM population in terms of most normal and disease phenotypes. Intratumor heterogeneity affects and profiling technology and reference human genome specifics affect <1% of the classifications of the tumors by the pattern, where experimental batch effects normally reduce the reproducibility, i.e., precision, of classifications based upon between one to a few hundred genomic loci by >30%. With a 2.25-year Kaplan–Meier median survival difference, a 3.5 univariate Cox hazard ratio, and a 0.78 concordance index, i.e., accuracy, the pattern predicts survival better than and independent of age at diagnosis, which has been the best indicator since 1950. The prognostic classification by the pattern may, therefore, help to manage GBM pseudoprogression. The diagnostic classification may help drugs progress to regulatory approval. The therapeutic predictions, of previously unrecognized targets that are correlated with survival, may lead to new drugs. Other methods missed this relationship in the roughly 3B-nucleotide genomes of the small, order of magnitude of 100, patient cohorts, e.g., from TCGA. Previous attempts to associate GBM genotypes with patient phenotypes were unsuccessful. This is a proof of principle that the frameworks are uniquely suitable for discovering clinically actionable genotype–phenotype relationships.

First-iGAP: A Randomized Placebo-Controlled Phase II Study of First-line Intercalated Gefitinib and Pemetrexed-Cisplatin Chemotherapy for Never-Smoker Lung Adenocarcinoma Patients

BackgroundWe aimed to evaluate whether intercalated combination of EGFR tyrosine kinase inhibitor gefitinib and chemotherapy improves survival outcomes in never-smokers with advanced lung adenocarcinoma. Patients and MethodsNever-smokers with chemo-naive stage IIIB/IV lung adenocarcinoma were randomly assigned to receive either gefitinib or placebo on days 5 to 18 of a 3-weekly cycle of pemetrexed and cisplatin. Chemotherapy was given up to 9 cycles, after which gefitinib or placebo was given daily. Patients in the placebo arm who had progression were crossed over to receive gefitinib. ResultsBetween June 2012 and December 2014, 76 patients with median age of 58.0 years were randomized, 39 on gefitinib and 37 on the placebo arm. EGFR mutation was positive in 34 (44.7%) patients. Baseline characteristics were well balanced between the 2 arms. The gefitinib arm had a better response rate (79.5% vs. 51.4%, P = .010) and median progression-free survival (PFS) (12.4 vs. 6.7 months, hazard ratio [HR] 0.49, P = .005) than the placebo arm; however, there was no statistically significant difference in median overall survival between the 2 arms (31.8 vs. 22.9 months, HR 0.78, P = .412). The PFS benefit of intercalated use of gefitinib over placebo was more apparent for patients with EGFR-mutant tumors (13.3 vs. 7.8 months, P = .025) than those with EGFR–wild-type tumors (8.2 vs. 6.6 months, P = .063). Overall, there was no difference in the frequency of severe adverse effect between the 2 arms. ConclusionsIntercalated combination of gefitinib with pemetrexed and cisplatin was well tolerated and improved PFS in never-smoker patients with lung adenocarcinoma.