tbuckley/cabot-search huggingface dataset:
The impact of single-hetero UGT1A1 on clinical outcomes of irinotecan monotherapy in gastric cancer after fluoropyrimidine, platinum, and taxanes: Multicenter retrospective study.
Authors: Ken Ito, Yoshito Komatsu, Satoshi Yuki, Shintaro Nakano, Hiroshi Nakatsumi, Yasuyuki Kawamoto, Tetsuhito Muranaka, Kentaro Sawada, Takayuki Ando, Shinya Kajiura, Takuto Miyagishima, Kazuaki Harada, Yoshimitsu Kobayashi, Kazuteru Hatanaka, Atsushi Ishiguro, Takuya Honda, Masayoshi Dazai, Takahide Sasaki, Naoya Sakamoto
Journal: Journal of Clinical Oncology (2020)

296 Background: Japanese gastric cancer treatment guidelines (5th edition) recommend irinotecan (IRI) after fluoropyrimidine, platinum and taxanes as a third line chemotherapy. We previously reported that patients with UGT1A1 single heterozygous (SH) had significantly high frequency of severe hematological adverse events (AEs) compared to patients with UGT1A1 wild type (WT) in IRI monotherapy for advanced gastric cancer (AGC). However, it remains unclear that UGT1A1 SH affect efficacy and safety of IRI after fluoropyrimidine, platinum and taxanes compared to WT as a salvage line. Methods: We retrospectively analyzed the clinical data of patients who received IRI monotherapy after fluoropyrimidine, platinum and taxanes in the multi-institutional retrospective study. From January 2010 to December 2017, 69 eligible patients were registered from 8 centers in Japan. Results: Forty one patients with UGT1A1 WT and 28 patients with UGT1A1 SH were included in this study. In WT/SH patients, performance status 0/1/≥2 was 12/25/4 and 5/17/6, treatment line 3rd/4th or later was 33/8 and 26/2, HER2 status positive/negative was 12/29 and 5/23, respectively. In WT/SH patients, rate of initial dose reduction was 22 and 28% (P = 0.363), median relative dose intensity (RDI) was 82% and 80% (P = 0.309). Of 88 patients who have measurable lesions, the overall response rate (ORR) was 5.7% and 4.2% (P = 1.000), disease control rate (DCR) was 54% and 38% (P = 0.289). Median progression free survival was 3.2 and 2.1 months (HR 0.607, P = 0.058) and median overall survival from initial day of IRI monotherapy was 10.0 and 7.0 months (HR 0.618 P = 0.086). In WT/SH patients, severe hematological AEs (≥G3) were observed more frequently in patients with UGT1A1 SH (WT: 43% and SH: 68%, P = 0.050), although frequency of severe non-hematological AEs (≥G3) were not significantly different in both groups (13% and 25%, P = 0.211). Conclusions: Compared to UGT1A1 WT, UGT1A1 SH status may be associated with poor efficacy and be a risk factor of higher frequency of severe hematological AEs.
A phase II study of neoadjuvant chemotherapy with DCS for resectable advanced esophageal cancer.
Authors: Junya Kitadani, Masaki Nakamura, Toshiyasu Ojima, Masahiro Katsuda, Keiji Hayata, Hiroki Yamaue
Journal: Journal of Clinical Oncology (2020)

366 Background: The current standard treatment for clinical stage II/III esophageal cancer is neoadjuvant chemotherapy (NAC) with CDDP/5-FU (CF) regimen followed by surgery. However, to improve the survival of patients with advanced ESCC, more effective regimens are urgently needed. Triplet regimens containing docetaxel have been one of next candidates for advanced ESCC. Methods: The DCS regimen (Docetaxel 40mg/m2/day Day 1 div, CDDP 60mg/m2/day Day 1 div, S-1 80mg/m2/day Day 1~14 civ) was repeated every 4weeks until toxicity became unacceptable, the patient refused treatment, or disease progression was observed to a maximum of 3cycles. In this phase II trial of DCS, the primary endpoint was pathological response rate. Results: 40 patients were enrolled in this study and finally 39 patients underwent surgery and one patient performed chemoradiotherapy because of patient refusal. cT3 was 85%, cStage III and IV were 90%. Far advanced cases were in this study. Surgical complication was not increased compared to the historical data. R0 resection rate was achieved in 85%. The clinical response rate was 76%. Pathological response rate was 33%, which was the primary endpoint. 2-year recurrence-free survival rate was 56% and 2-year overall survival rate was 71%. The rate of Grade 3 or 4 Neutropenia was 69%, and FN was 18%. NAC-DCS was high toxic regimen, but manageable regimen. The median time of onset with Grade 3/4 neutropenia was day 11 from start of each cycle. Conclusions: NAC with DCS regimen was feasible and good response for advanced ESCC and became to a promising candidate. Further, the survival benefit of triplet regimen including S-1 should be verified by the randomized controlled trial. Clinical trial information: UMIN000017153.
Clinical and pathologic characteristics of early-onset colorectal cancer (EoCRC).
Authors: Arif Ahmad Arif, Daljeet Chahal, Caroline Speers, Sharlene Gill, Fergal Donnellan, Jonathan M. Loree
Journal: Journal of Clinical Oncology (2020)

72 Background: Although CRC incidence continues to fall in patients over 50 due to adoption of screening programs, there has been an increasing incidence in patients &lt; 50 where screening does not occur. We investigated the clinical and pathologic characteristics of EoCRC in BC. Methods: We retrospectively analyzed 27612 patients diagnosed with CRC and referred to BC Cancer between 1990-2016. Patients &lt; 50 were classified as early onset CRC and analyzed for baseline and disease characteristics. Results: In the 2540/27612 (9.2%) of patients &lt; 50, patients were more likely to be female (OR 1.33, 95% CI 0.61-1.44, P &lt; 0.0001), have left sided tumors (OR 1.50, 95% CI 1.35-2.01, P &lt; 0.0001), have poorly differentiated tumors (OR 1.24, 95% CI 1.10-1.34, P = 0.0003), and more patients presented with metastatic disease (OR 1.26, 95% CI 1.15-1.38, P &lt; 0.0001) compared to patients ≥50. At diagnosis, patients &lt; 50 were more likely to have a significant complication related to the primary tumor (OR 1.18, 95% CI 1.06-1.32, P = 0.0041), specifically, greater rates of perforation (OR 1.84, 95% CI 1.47-2.31, P &lt; 0.0001). Although high risk features used to guide adjuvant therapy decisions in patients &lt; 50 with stage II CRC were not higher, with similar T4 prevalence, poor differentiation, lymphovascular and perineural invasion, and less inadequate lymph node harvesting (≤12) (all p &gt; 0.05), rates of adjuvant therapy were higher (OR 2.39, 95% CI 1.91-3.00, P &lt; 0.0001). This was also noted in stage III CRC (OR 4.11 95% CI 3.07-5.48, P &lt; 0.0001). Age impacted overall survival, with younger patients of all stages living longer (HR 0.72, 95% CI 0.68-0.76, P &lt; 0.0001). Similar findings were noted for stage I-III CRC (HR 0.54 0.50-0.58, P &lt; 0.0001) and for patients once they became metastatic (HR 0.84 95% CI 0.75-0.93, P = 0.0025). To control for competing causes of death, we looked at disease specific survival, which continued to show improved outcomes for patients age &lt; 50 in stage I-III (HR 0.88 95% CI 0.81-0.97, P = 0.0016) and stage IV (HR 0.77 95% CI 0.72-0.84, P &lt; 0.0001) CRC. Conclusions: EoCRC patients present with unique clinical and pathologic characteristics which may impact outcome. While the population &lt; 50 has comparable outcomes, they may undergo increased rates of treatment.
A real-world application of liquid biopsy (LB) in metastatic colorectal cancer (mCRC).
Authors: Letizia Procaccio, Marzia Del Re, Stefania Crucitta, Giulia Gianfilippo, Francesca Daniel, Veronica Di Antonio, Sara Gallimberti, Giada Munari, Giulia Zanella, Giulia Alberti, Mario Domenico Rizzato, Cosimo Rasola, Giulia Maddalena, Alessandra Anna Prete, Francesca Bergamo, Vittorina Zagonel, Sara Lonardi, Romano Danesi, Matteo Fassan, Fotios Loupakis
Journal: Journal of Clinical Oncology (2020)

48 Background: First-line decision making is the key to the successful management of mCRC patients (pts). RAS/BRAF status is essential to choose the best targeted agent. In hub centers, a not negligible proportion of pts referred from elsewhere may not have standard tissue-based (STB) molecular results available at the time of first oncologic visit (T0). LB may help circumvent these hurdles. Methods: A monoinstitutional prospective head-to-head comparison of LB versus (vs) STB testing was conducted in a real-world setting. Selection criteria included: mCRC with unknown RAS/BRAF status at T0, tissue from primary or metastases archived in external centers, no previous anti- EGFR agents. At T0, pts underwent plasma sampling for LB testing and procedure for tissue recovery. RAS/BRAF genotyping was carried out by droplet digital PCR on circulating-free (cf) DNA. Primary endpoint was the comparison of time to LB (T1) vs STB (T2) results. Secondary endpoints were the overall percent agreement (OPA), specificity, sensitivity, positive and negative predictive value (PPV and NPV) of LB. Urinary (u) cfDNA testing was also explored. Results: A total of 33 pts were included. Mean T1 was 7 (2-12) days (d) as compared to 22 (7-65) d mean T2. T2 included a mean time for tissue recovery of 17 d. The OPA between LB and STB analysis was 83%. Compared to STB testing, LB specificity and sensitivity were 90% and 80%, respectively, with a PPV of 94% and NPV of 69%. In detail, at STB and LB testing, RAS mutation was found in 50% and 43% of pts; BRAF mutation in 17% and 13%, respectively. LB results included 1 false positive and 4 false negative (FN). FN showed a significantly lower tumor burden (i.e. total tumor volume) at basal CT scan. Concordance between STB and ucfDNA testing was 89%, with a sensitivity of 83% and specificity of 100% recorded for ucfDNA analysis. Conclusions: Faster turnaround time, high concordance and accuracy are 3 key-points supporting the adoption of LB in routinary mCRC care, in particular when decision on first-line is urgent and tissue recovery from external centers may require a long time. Results should be interpreted with caution in LB wild-type cases with low tumor burden.
The role of immunotherapy on the survival of pancreatic cancer patients.
Authors: Saber Ali Amin, Michael Baine, Jane L. Meza, Chi Lin
Journal: Journal of Clinical Oncology (2020)

714 Background: Immunotherapy has revolutionized the treatment landscape of many malignancies, but its therapeutic role in pancreatic cancer (PC) remains unclear. The objective of this study is to investigate the impact of immunotherapy on the overall survival of PC patients stratified by definitive surgery of the pancreas using the National Cancer Database (NCDB). Methods: Patients with pancreatic adenocarcinoma were identified from NCDB. Cox proportional hazard models were employed to assess the impact of immunotherapy on survival after being stratified by surgery and adjusted for age of diagnosis, race, sex, place of living, income, education, treatment facility type, insurance status, year of diagnosis, and treatment types such as chemotherapy and radiation therapy. Results: Of 252,280 patients who were analyzed, 214,632 (85.08%) had definitive surgery, and 37,638 (14.92%) did not get definitive surgery of the pancreas. In the surgery group, 351 (0.93%) received immunotherapy and 37,287 (99.07%) did not while in the no surgery group, 838 (0.39%) received immunotherapy and 213,804 (99.61%) did not. In the multivariable analysis, patients who received immunotherapy had significantly improved OS both in the no surgery group (HR: 0.886, CI: 0.655-0.714; P &lt; 0.0001) and in the surgery group (HR: 0.846, CI: 0.738-0.971; P &lt; 0.0001) compared to patients who did not receive immunotherapy. Treatment with chemotherapy plus immunotherapy was associated with significantly improved OS (HR: 0.871, CI: 0.784-0.967; P &lt; 0.009) compared to chemotherapy without immunotherapy in the no surgery group, while it was not significant in the surgery group. Chemoradiation plus immunotherapy was associated with significantly improved OS (HR: 0.787, CI: 0.684-0.906; P &lt; 0.0009) in the no surgery group and (HR: 0.799, CI: 0.681-0.938) in the surgery group compared to chemoradiation alone. Conclusions: In this study, the addition of immunotherapy to chemoradiation therapy was associated with significantly improved OS in PC patients with or without definitive surgery. The study warrants further future clinical trials of immunotherapy in PC.
Subsequent anticancer procedures following first-line lenvatinib (LEN): A post hoc analysis from the phase III REFLECT study in unresectable hepatocellular carcinoma (uHCC).
Authors: Angel Alsina, Masatoshi Kudo, Arndt Vogel, Ann-Lii Cheng, Won Young Tak, Baek-Yeol Ryoo, T.R. Jeffry Evans, Carlos Lopéz Lopéz, Bruno Daniele, Jean-Frédéric Blanc, Min Ren, Rae Lynn Baldwin, Namiki Izumi, Shukui Qin, Richard S. Finn
Journal: Journal of Clinical Oncology (2020)

520 Background: The availability of newer therapeutic options has shifted the treatment paradigm for uHCC, evoking questions regarding the sequencing of anticancer therapies. REFLECT was a phase 3 study comparing the efficacy and safety of LEN versus sorafenib (SOR) in first-line treatment of patients (pts) who have uHCC. In this post hoc analysis, we investigated overall survival (OS) during the follow-up survival period between treatment arms for pts who did and did not receive subsequent anticancer procedures and for responders to first-line LEN who received subsequent anticancer procedures. Methods: Pts in REFLECT were randomized 1:1 to LEN or SOR. The follow-up period commenced at the first visit after stopping study medications. Pts were followed-up every 12 weeks until data cutoff (Nov 13, 2016) or death. OS was estimated using the Kaplan–Meier method and presented with a 95% confidence interval (CI). Pts receiving subsequent radiotherapy were excluded from the OS analysis. Results: Of the 954 pts enrolled in REFLECT, 122/478 (26%) LEN- and 130/476 (27%) SOR-treated pts received subsequent anticancer procedures, with the most common being transarterial chemotherapy embolization (LEN n = 69 [14.4%]; SOR n = 81 [17.0%]) and hepatic intra-arterial chemotherapy (LEN n = 23 [4.8%]; SOR n = 25 [5.3%]). Eastern Cooperative Oncology Group performance status scores and laboratory assessments, including liver function, were comparable between arms at first-line treatment discontinuation. Of the pts who received subsequent anticancer procedures, those randomized to first-line LEN (n = 99) had a longer median OS (23.0 vs 19.6 months, respectively; hazard ratio [HR]: 0.71; 95% CI: 0.51–1.01) than those randomized to first-line SOR (n = 112). Responders to first-line LEN who received subsequent anticancer procedures (n = 45) had a median OS of 27.2 months (95% CI: 20.7–29.8). There were too few SOR responders (n = 10) who received subsequent anticancer procedures to evaluate OS. Conclusions: Pts randomized to first-line LEN who received subsequent anticancer procedures had longer OS compared with the similar sequence for pts taking first-line SOR. Clinical trial information: NCT01761266.
Atypical Stevens-Johnson syndrome-like reaction in the setting of immune checkpoint inhibition.
Authors: Gabriel E. Molina, Zizi Yu, Ruth K. Foreman, Kerry Lynn Reynolds, Steven T. Chen
Journal: Journal of Clinical Oncology (2020)

102 Background: Stevens-Johnson syndrome (SJS) is a rare, life-threatening mucocutaneous toxicity that can occur in patients receiving immune checkpoint inhibitors (ICIs). ICI-induced SJS is scarcely reported in the literature and thus remains poorly understood, particularly regarding features that may distinguish it from classic SJS. Methods: To describe the timing, clinical manifestations, and treatment course of ICI-induced SJS, this multicenter, retrospective study identified seven patients with SJS in the setting of ICI use from January 2011 through May 2019. Results: All seven patients presented initially as benign, limited drug eruptions after a median of 4 ICI cycles (range, 1-7) and 63 days (range, 13-253 days) from ICI initiation. While none of the patients had prior drug allergies, all 7 were receiving new, recently initiated – i.e., within two months – medications at the time of rash onset. Cases demonstrated characteristic histologic findings of SJS, such as epidermal necrosis, and occasional unusual features, including interface dermatitis. All patients responded favorably and rapidly to systemic therapy, primarily intravenous corticosteroids, with near immediate symptomatic resolution and cessation of progressive skin blistering or detachment. Median length of stay was 11 days and no patients died from SJS. Conclusions: Our cohort defines an atypical SJS-like reaction secondary to ICI use, which is distinct from classic SJS in its delayed onset, mild initial presentation, and rare ocular involvement. The association with concomitant medication use suggests a potential mechanism whereby ICIs reduce patient immune tolerance to subsequent drug exposures. Reassuringly, this atypical SJS-like phenomenon exhibits a benign clinical course and favorable response to standard treatments.
Feasibility and clinical impact of routine molecular testing of gastrointestinal (GI) cancers at a tertiary center with a multigene, next generation sequencing (NGS) panel.
Authors: Giacomo Bregni, Tiberio Sticca, Tugba Akin Telli, Silvia Camera, Ligia Ioana Craciun, Leila Shaza, Amélie Deleruelle, Maëlle Anciaux, Godelieve Machiels, Amélie Deleporte, Caroline Vandeputte, Pieter Demetter, Denis Larsimont, Alain Hendlisz, Francesco Sclafani
Journal: Journal of Clinical Oncology (2020)

216 Background: High-throughput technologies have been increasingly used in research. Nevertheless, limited data are available on the feasibility and clinical value of these technologies in routine practice. Methods: All consecutive GI cancer patients (pts) who were tested with the 48-gene Truseq Amplicon Cancer Panel (Illumina) as part of routine practice at our Institution were identified from a prospectively maintained pathology database. Feasibility, results and impact on management decisions were analysed. Associations were tested with Fisher’s test. Results: From Apr 2014 to Jun 2019, 314 pts were tested. Sequencing was successful in 290 cases (92.4%; 234 colorectal (CRC), 21 gastro-esophageal, 17 bilio-pancreatic, 9 GIST, 4 appendix, 3 small intestine, 2 hepatocellular). In successful and failed cases, respectively, analyses were attempted on core biopsy (37.0% vs 66.7%), surgery (62.6% vs 16.7%), and fine needle aspiration (0.4% vs 12.4%) tumour samples (p &lt; 0.001). Median turnaround time (TAT) was 12.5 days, reducing from 13 days in 2014 to 10 days in 2019. The majority of successfully tested pts (85.6%) had stage IV disease. TP53 was the most frequent mutation (45.9%), followed by APC (42.1%), KRAS (39.7%), PIK3CA (12.1%), SMAD4 (7.6%), BRAF (6.2%), and NRAS (5.5%). All other mutations were found in &lt; 5% of cases. Excluding RAS/BRAF and KIT/PDGFR mutations, sequencing results impacted on the management of 4 (1.4%) pts. In 199 stage IV CRC pts, KRAS mutations were associated with lung (p = 0.020) and bone metastases (mts) (p = 0.008), NRAS mutations with liver mts (p = 0.021), BRAF mutations with peritoneal mts (p = 0.001), and APC mutations with lymph node mts (p = 0.006). Assuming a median of 25 samples per run, the estimated cost of NGS analysis per pt was €186. Conclusions: Low failure rate, short TAT and fair costs support feasibility of multi-gene NGS in routine practice. The clinical impact of this technology, however, is still limited but it could raise with the identification of new biologically relevant genetic alterations and the increased availability of novel therapeutics.
Does nutritional status affect treatment tolarability, response, and survival in metastatic colorectal cancer patients? Results of prospective multicenter study.
Authors: Senem Karabulut, İzzet Dogan, Çiğdem Usul Afşar, Mehmet Karabulut, Sule Karaman, Ferhat Ferhatoglu, Didem Tastekin
Journal: Journal of Clinical Oncology (2020)

70 Background: The efficacy and tolerability of modern cytotoxic chemotherapy regimens used in malnourished metastatic colorectal cancer patients is uncertain. The aim of this study was to investigate the effect of malnutrition on efficacy and tolerability of cytotoxic chemotherapy and overall survival in mCRC patients. Methods: In this multicenter study, demographic, oncologic and nutritional data were collected prospectively from mCRC patients. Nutritional status were evaluated on the basis of NRI, BMI and WL before the first chemotherapy, after the first and second chemotherapy. To determine the inter-treatment weight loss toxicity assessment was included to theese parameters after each chemotherapy. NRIs were examined in 3 categories as ‘no malnutrition’ (NRI &gt;97.5), ‘moderate malnutrition’ (97.5 ≥ NRI ≥83.5) or ‘severe malnutrition’ (NRI &lt;83.5). Response to treatment and drug-induced toxicities were assessed based on RECIST 1.1 and CTCAE version 4.0 respectively. Results: 137 mCRC patients were prospectively included. Median age was 48 (range 18-83). Primary location was colon in 66% of patients, 84% of them source was left colon. Malnutrition was detected in 39% of the cases. Response rate to treatment was 24 %. Moderate / severe malnutrition was associated with multipl site of metastases, WHO PS of 1, over the median value of CEA/CA 19-9 levels (p=0.003, p=0.03, p&lt;0.001, and p=0.02; respectively). Hypoalbuminemia and moderate/severe malnutrition were associated with all types of toxicity (p&lt;0.001 and p&lt;0.001). Moderate/severe malnutrition was associated with thrombocytopenia, and diarrhea following chemotherapy predominately, (p=0.02 and p=0.04; respectively). In moderate/severe malnutrition group median overall survival was prominently shorter than those with no malnutrition [6.6 moths (95 %CI, 5.6-7.6) vs 11.9 moths (95 % CI, 11.1-12.7) respectively, p&lt;0.001]. Conclusions: Our study showed that moderate/severe malnutrition in mCRC patients was associated with decreased overall survival and increased chemotherapy toxicity.
Clinicopathological features of multifocal gastric carcinoma: A retrospective study.
Authors: Xi Zou, Runfeng Zhang, Qi Lei, Aiping Zhou, Chun-Xia Du
Journal: Journal of Clinical Oncology (2020)

453 Background: The occurrence of multifocal gastric carcinoma (MGC) is growing in China, while relevant study remains limited. This study aimed to collect more information of MGC for further research. Methods: Patients with MGC treated at China National Cancer Center from January 2010 to December 2017 were enrolled in this retrospective study. A 6-month interval was used to separate synchronous and metachronous foci. Results: 103 patients were included. 88 (85.4%) were males. 96 (93.2%) patients had two foci and 7 (6.8%) had three or more foci, contributing a total of 216 tumor foci. 185 (85.6%) foci were adenocarcinoma, 18 (8.3%) were intraepithelial neoplasia, 2 (0.9%) were lymphoepithelioma-like carcinoma and 1 (0.5%) was small cell carcinoma. Intestinal, diffuse, and mixed type accounted for 49.7%, 14.6% and 11.4% respectively, with 24.3% unknown.In 96 patients with 2 foci, 56 (58.3%) patients had synchronous diseases, and 40 (41.7%) had metachronous diseases. The median age at the diagnosis of first tumor was 62 (55-71) years. The median diagnosis interval of metachronous tumor foci was 41.4 (23.5-88.3) months. The locations and sizes of foci are shown in Table. In synchronous cases, 6 foci of accessory tumor were less than 1cm including one being 0.4 cm. In metachronous cases, 4 foci of second tumor were less than 1 cm. 51 (49.5%) patients were current smokers or ex-smokers, and 44 (42.7%) were regular alcohol consumers. 26 (25.2%) patients had a first-relative family history, including 14 (13.6%) having a family history of gastrointestinal carcinoma. Conclusions: The second gastric tumor should be thoroughly detected to avoid missed diagnosis, since the accessory tumor might be rather small. Further genetic research is warranted to explore the potential pathogenesis of MGC. [Table: see text]