tbuckley/cabot-search huggingface dataset:
Denosumab and zoledronic acid treatment in patients with genitourinary cancers and bone metastases.
Authors: Luis Costa, Karim Fizazi, Fred Saad, Janet Elizabeth Brown, Roger Von Moos, Stephane Oudard, Cora N. Sternberg, Vinod Ganju, Kurt Miller, Huei Wang, Tapan Maniar, Ada Braun
Journal: Journal of Clinical Oncology (2013)

5079 Background: Phase III trial results showed that denosumab is superior to zoledronic acid (ZA) in preventing skeletal-related events (SREs) in patients with cancer and metastatic bone disease (Lipton et al; 2012, Eur J Cancer). Genitourinary (GU) cancers are some of the most commonly diagnosed cancers worldwide. We now compare the efficacy and safety of denosumab (DMAb) or ZA in a subgroup analysis of patients with GU cancers enrolled in the pivotal phase III trials. Methods: Patients were randomized 1:1 to receive DMAb (120 mg, SC) or ZA (4 mg, IV, adjusted for renal function) every 4 weeks. Daily calcium and vitamin D supplements were strongly recommended. Time to 1st on-study SRE, using a Cox proportional hazards model, time to 1st and subsequent on-study SRE, using the Anderson-Gill model, and safety were evaluated for the GU subgroup in an ad hoc analysis. Results: 2,128 patients (1,052 DMAb; 1,076 ZA) had GU cancers (prostate = 1,901, renal = 155, bladder = 63, and transitional cell = 9). DMAb significantly delayed the time to 1st on-study SRE by 4.0 months compared with ZA (20.7 months vs 16.7 months) in patients with GU cancers (Table). DMAb also significantly delayed the time to 1st and subsequent on-study SRE. Time to disease progression and overall survival were similar between treatment groups. Adverse events (AEs) and serious AEs were reported by similar percentages of patients in both groups (AEs: 96.9% denosumab, 96.8% ZA; serious AEs: 62.8% denosumab, 60.2% ZA). 14.6% of DMAb pts and 15.9% of ZA pts had a renal AE. Hypocalcemia was reported for 12.9% of DMAb patients and 6.2% of ZA patients. There was no significant difference in the incidence of positively adjudicated osteonecrosis of the jaw between the DMAb (2.2%) and ZA (1.6%) groups (p=0.34). Conclusions: Among patients with GU cancers and metastatic bone disease, DMAb was superior to ZA in preventing SREs. Clinical trial information: NCT00330759 and NCT00321620. [Table: see text]
Clinical impact of visceral thrombosis (VT) in pancreatic ductal adenocarcinoma (PDAC).
Authors: Angel Mier Hicks, Micheal Raj, Richard Kinh Gian Do, Kenneth H. Yu, Maeve Aine Lowery, Anna M. Varghese, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2017)

260 Background: VT or splanchnic thrombosis is defined as thrombi within the hepato-portal venous system including; portal (PV), mesenteric (MV) and splenic vein (SV), as well as thrombi in renal or gonadal veins. Limited evidence has explored the prognostic significance, incidence and current clinical management of VT in patients with PDAC. Methods: We conducted an analysis of N = 95 patients treated at Memorial Sloan Kettering Cancer Center diagnosed between 1/1/13 and 12/31/15 with PDAC who developed a VT either at presentation or which developed during the disease course. Results: N = 134 VT events (VTe) occurred. Median age of PDAC diagnosis was 62.5 yrs. Overall survival (OS) was 10.5 months (m); seven patients were still alive in 7/ 16. Time to develop first VTe was 4.3m (SD6.71, 0-31) and time to death from VTe development was 6.1m (SD 5.7,0-24). Subsequently, N = 42 pts developed a second VTe and N = 13 pts a third VTe. At time of VT diagnosis, N = 37 (38%) pts were asymptomatic, and N = 58 (61%) pts had an incidental finding. N = 39 (39%) pts were treated with short-term anticoagulation (STAC) ( &lt; 1m) (N = 35 pts, treated with Low Molecular Weight Heparin (LMWH)). N = 45(46%) pts were treated with long-term anticoagulation (LTAC) ( &gt; 1m) (LMWH N = 32, N = 11 pts were transitioned to an oral anticoagulant (NOAC)). Only N = 12(12%) pts were treated with a NOAC. N = 8 (8%) pts developed a bleeding complication from LTAC. OS for pts receiving LTAC was 4m vs 3m with STAC. Conclusions: In patients with PDAC, VT can frequently present as an incidental finding on routine abdominal imaging. The most common location is PV followed by MV and SV. We observed that AC is under-utilized in this setting despite a low bleeding complication rate. LMWH appeared to be the preferred treatment with LTAC, followed by use of a NOAC. PV was associated with reduced OS. Use of therapeutic anticoagulation for treatment of VT is limited by lack of data. Future large prospective studies should explore the role of AC and value in this setting.[Table: see text]
Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response in castration-resistant patients.
Authors: Camilla Thellenberg Karlsson, Lee-ann Tjon-Kon-Fat, Marie Lundholm, Mona Schröder, Thomas Wurdinger, Anders Widmark, Jonas Nilsson, Pernilla Wikström
Journal: Journal of Clinical Oncology (2017)

e583 Background: Novel therapies for castration resistant prostate cancer (CRPC) have been introduced in the clinic with possibilities for individualized treatment plans. Best practice of those expensive drugs requires predictive biomarker monitoring. This study used circulating biomarker analysis to follow cancer-derived transcripts implicated in therapy resistance. Methods: The isolated platelet population of blood samples and QRT-PCR were used to identify selected biomarker transcripts in patients with CRPC prior chemo- or androgen synthesis directed therapies. The association between biomarker status in platelets (positive vs. negative) and therapy response, progression-free survival (PFS) and overall survival (OS) was examined. Results: Fifty patients received either docetaxel (n = 24) or abiraterone (n = 26) therapy, with therapy response rates of 54% and 48%, respectively. Transcripts for the PC-associated biomarkers kallikrein-related peptidase-3 ( KLK3), androgen receptor splice-variant 7 (ARV7), folate hydrolase 1 (FOLH1), and neuropeptide-Y ( NPY) were present within the platelet fraction. Analyzing biomarkers in the chemotherapy group did not add information about PFS, but FOLH1 was associated with short OS (p = 0.00015). In the abiraterone treated cohort, detectable FOLH1 (p = 0.009), KLK3 (p = 0.018), and NPY (p = 0.028) were all associated with short PFS. Patients with biomarker-negative platelets had the best outcome, while FOLH1 and NPY provided independent predictive information regarding PFS and KLK3 (p = 0.001) and FOLH1 (p = 0.002) were associated with short OS. Conclusions: Analyzing tumor-derived biomarkers in platelets of CRPC patients enabled prediction of the outcome after abiraterone therapy with high accuracy. Platelet-based analysis of FOLH1, NPY, and KLK3 may be used for treatment stratification of patients scheduled for treatment with abiraterone.
Predictive Properties of Biomarkers GDF-15, NTproBNP, and hs-TnT for Morbidity and Mortality in Patients With Type 2 Diabetes With Nephropathy
Authors: Arash Bidadkosh, Sebastiaan P.H. Lambooy, Hiddo J. Heerspink, Michelle J. Pena, Robert H. Henning, Hendrik Buikema, Leo E. Deelman
Journal: Diabetes Care (2017)

OBJECTIVE Although patients with type 2 diabetes (T2D) with nephropathy are at high risk for renal and cardiovascular complications, relevant biomarkers have been poorly identified. Because renal impairment may increase biomarker levels, this potentially confounds associations between biomarker levels and risk. To investigate the predictive value of a biomarker in such a setting, we examined baseline levels of growth differentiation factor-15 (GDF-15), N-terminal prohormone of B-type natriuretic peptide (NTproBNP), and high-sensitivity troponin T (hs-TnT) in relation to renal and cardiovascular risk in T2D patients with nephropathy. RESEARCH DESIGN AND METHODS Eight hundred sixty-one T2D patients from the sulodexide macroalbuminuria (Sun-MACRO) trial were included in our post hoc analysis. Prospective associations of baseline serum GDF-15, NTproBNP, and hs-TnT with renal and cardiovascular events were determined by Cox multiple regression and C-statistic analysis. Renal base models included albumin-to-creatinine ratio (ACR), serum creatinine, hemoglobin, age, and sex. Cardiovascular base models included diastolic blood pressure, ACR, cholesterol, age, and sex. RESULTS The mean (±SD) estimated glomerular filtration rate was 33 ± 9 mL/min/1.73 m2, and the median serum concentration for GDF-15 was 3,228 pg/mL (interquartile range 2,345–4,310 pg/mL), for NTproBNP was 380 ng/L (155–989 ng/L), and for hs-TnT was 30 ng/L (20–47 ng/L). In multiple regression analysis, GDF-15 (hazard ratio [HR] 1.83, P = 0.04), NTproBNP (HR 2.34, P = 0.004), and hs-TnT (HR 2.09, P = 0.014) were associated with renal events, whereas NTproBNP (HR 3.45, P &amp;lt; 0.001) was associated with cardiovascular events. The C-statistic was improved by adding NTproBNP and hs-TNT to the renal model (0.793 vs. 0.741, P = 0.04). For cardiovascular events, the C-statistic was improved by adding NTproBNP alone (0.722 vs. 0.658, P = 0.018). CONCLUSIONS Biomarkers GDF-15, NTproBNP, and hs-TnT associate independently with renal risk, whereas NTproBNP independently predicts cardiovascular risk.
A broad Italian experience with eribulin mesylate in metastatic breast cancer patients: The ESEMPiO study.
Authors: Sandro Barni, Caterina Fontanella, Lucia Del Mastro, Luca Livraghi, Laura Pizzuti, Maria Morritti, Stefania Eufemia Lutrino, Mariangela Ciccarese, Ornella Garrone, Andrea Michelotti, Agnese Latorre, Loretta d'Onofrio, Arianna Pellegrino, Vita Leonardi, Laura Iezzi, Nicla Maria La Verde, Mario Airoldi, Marco Pistelli, Francesca Martella, Luca Porcu
Journal: Journal of Clinical Oncology (2015)

e11539 Background: Eribulin Mesylate (EM) has been available in Italy since January 4th, 2012 for the treatment of patients (pts) with metastatic breast cancer (MBC) after the failure of at least 2 chemotherapy lines. In order to evaluate the efficacy and safety of EM, we designed a multicenter observational study in a real-world cohort of MBC patients. Methods: Patients who received at least one administration of EM from January 2012 to December 31st, 2013 were included. All data were updated to 31st March 2014. Results: A total of 497 pts received EM in 39 Italian centers. At the time of MBC diagnosis, the median age was 54.5 years (range: 24.1-78.5). Overall, 82.8% of patients were diagnosed with ductal breast cancer (lobular 10.7% others 6.5%), 79.9% were ER/PgR+, 13.0% triple negative, and 7.1% HER2+. In our analysis, 13.1% of pts received EM as third line, 19.3% as fourth line, and 60.4% as ≥ fifth line (median number of EM lines: 5, range: 1-9). In third line, the median number of cycles was 4 (range: 1-20), in fourth line was 3 (range: 1-19) and ≥ fifth line was 4 (range: 1-19); the median number of cycles was 4 (range: 1-20). Overall, at a median follow-up of 7.5 years from MBC diagnosis, 62.4% of pts died. Median overall survival (OS) from MBC diagnosis was 34.2 months (mos) (95%CI: 25.9-59.8 mos) for patients who received EM as third line, 40.7 mos (95%CI: 36.0-48.7 mos) for fourth line, and 71.6 mos (95%CI: 66.0-83.5 mos) for ≥ fifth line (median OS: 62.9 mos; 95%CI: 55.7-68.1 mos); while the median OS from EM treatment initiation was 12.6 mos (95%CI: 6.8-15.6 mos), 11.5 mos (95%CI: 6.6-14.8 mos), and 9.7 mos (95%CI: 8.7-11.5 mos) for the third, fourth and ≥ fifth lines respectively (median OS: 9.8 mos; 95%CI: 8.8-11.5 mos). The main reason for EM discontinuation was disease progression (87.4%), followed by toxicity (9.2%) and others (3.4%). Conclusions: Although Italian patients who received EM were more pre-treated (median number of lines: 5) compared with those of the study EMBRACE (median 4), the efficacy of EM has been confirmed. Considering the number of cycles performed and the low discontinuation of EM for toxicity also in advanced lines we can speculate that EM should always be included in the sequence of treatment for MBC.
From preclinical to phase II: Using virtual tumor clinical model to predict the efficacy of randomised phase II trials.
Authors: Eric Fernandez, Hitesh Mistry, Frances A Brightman, David Orrell, Daniele Giulio Generali, Manuela Milani, Alberto Bottini, Christophe Chassagnole
Journal: Journal of Clinical Oncology (2015)

e12032 Background: The translation of results from animal to man is a key phase in oncology drug development. Being able to determine efficacious doses and when to start taking key biopsy measurements are important for successful evaluation of a new drug within early clinical development. Furthermore, being able to accurately translate combination schedules from mouse to man would provide significant cost savings and accelerate clinical development. There is a clear unmet need for predictive tools to aid this process. Methods: We have developed a mathematical model of a tumour cell population called the Virtual Tumour, which has been used extensively to predict the efficacy of monotherapy or combination treatments in preclinical studies. We have now extended and adapted our preclinical model to predict efficacy in the clinic, thus creating the ‘Virtual Tumour Clinical’. The Virtual Tumour Clinical was successfully used to forward translate the efficacy of docetaxel/selumetinib combination vs docetaxel monotherapy used to treat melanoma in a phase II clinical trial using preclinical xenograft efficacy data. Here we present new sets of results highlighting the translational predictivity of Virtual Tumour Clinical. Results: Here we show a new case study where we predict clinical efficacy in a randomised phase II trial of different schedules of epirubicin as primary chemotherapy for breast cancer treatment. Model was first calibrated using preclinical PK and xenograft efficacy studies. Then, using key patient and literature data, preclinical settings were switched to clinical settings. Simulations of clinical efficacy were performed and predictions were then compared to actual results. Conclusions: Virtual Tumour Clinical is able to translate the effect of various antineoplastic agents in several indications, demonstrating the potential applicability of Virtual Tumour Clinical in translational science.
Associations between regorafenib-induced adverse events (AEs) and efficacy in metastatic colorectal cancer (mCRC).
Authors: Takeru Wakatsuki, Eiji Shinozaki, Mitsukuni Suenaga, Izuma Nakayama, Tomohiro Matsushima, Hiroki Osumi, Takashi Ichimura, Mariko Ogura, Daisuke Takahari, Masato Ozaka, Keisho Chin, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2017)

556 Background: It is occasionally recognized that, in molecular targeted therapy, target-specific AEs can surrogate its efficacy, such as skin toxicities and anti-EGFR antibodies. Because of multikinase inhibitor, regorafenib is involved in various kinds of adverse events; however, the clinical associations between AEs and efficacy remain unclear. The aim of this study is to reveal what AEs could surrogate efficacy of regorafenib. Methods: AEs were graded according to CTCAE ver. 4.0. We defined as “CRP increased”, if CRP increased more than 5 mg/dl during treatment compared with the baseline level. Time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier methods and compared by the log-rank test. Covariates which were significant in univariate analysis were included in multivariate analysis. Results: One-hundred and two patients were enrolled in this study. Almost all patients were PS 0-1 and received 160mg of regorafenib as an initial dose. The median TTF and the median OS were 2.0 and 8.0 months, respectively. Major AEs were Hand-foot skin reaction (HFSR) in 82.4% (≥Gr3:38.2%), Hypertension (HT) in 39.2% (16.7%), Rash in 23.5% (8.8%), Blood bilirubin increased (BBI) in 58.8% (2.9%), Thrombocytopenia in 48.0% (3.9%), Neutropenia in 20.5% (0%), and CRP increased in 46.1%. Regarding TTF, in univariate analysis, BBI, AST increased Gr0-1, neutropenia, absence of CRP increased, Diarrhea, HFSR, and Rash Gr0-2 were associated with longer TTF. In multivariate analysis, HFSR (HR 0.34 95%CI 0.19-0.63, p = 0.001) and Rash ≥Gr3 (HR 2.43 95%CI 1.13-5.21, p = 0.023) retained to be significant. With respect to OS, in univariate analysis, AST increased Gr0-1, ALT increased Gr0-1, neutropenia, absence of CRP increased, HFSR, and Rash Gr0-2 were associated with longer OS. In multivariate analysis, HFSR (HR 0.47 95%CI 0.24-0.91, p = 0.026), neutropenia (HR 0.54 95%CI 0.30-0.95, p = 0.032) and AST ≥Gr2 (HR 5.72 95%CI 2.11-15.63, p = 0.023) retained to be significant. Conclusions: HFSR and neutropenia might surrogate regorafenib efficacy in mCRC. Elucidation of the mechanisms of these AEs may help to understand which the pathway is the key role of regorafenib treatment in mCRC.
Correlation of <sup>64</sup>Cu-DOTA-trastuzumab positron emission tomography (PET) imaging with HER2 status by immunohistochemistry (IHC).
Authors: Joanne E. Mortimer, Jinha Mark Park, Mary I. Carroll, Kofi Poku, Joshua Miles, David Colcher, Andrew Antony Raubitschek, Tri Tran, James R. Bading
Journal: Journal of Clinical Oncology (2013)

TPS11121 Background: We have developed 64 Cu-DOTA-trastuzumab for PET imaging of HER2-positive breast cancer. We have determined that administering trastuzumab (45 mg) prior to 64 Cu-DOTA-trastuzumab sharply reduces liver uptake of the radiotracer. We are now testing whether tumor uptake of 64 Cu-DOTA-trastuzumab correlates with variable IHC staining in women with advanced breast cancer. Methods: Eligibility criteria included biopsy confirmation of metastatic disease that was HER2 1+, 2+, or 3+ by IHC, no anti-HER therapy within the prior 4 mo, and at least 1 non-hepatic site of metastasis &gt; 20 mm outside the biopsy site. Staging workup included 18 F-FDG PET-CT. Patients received 45 mg of cold trastuzumab prior to 64 Cu-DOTA-trastuzumab. PET-CT scans were obtained at 21-25 h (Day 1) and 47-48 h (Day 2) over axial fields of view chosen in reference to 18 F-FDG. Uptake in prominent lesions was measured in terms of maximum single-voxel SUV (SUV max ). Lesions identified on CT and judged to have image intensity &gt; adjacent tissue by an expert radiologist were considered positive on PET. Results: Fourteen women (median age 56, range 35-75 y) have undergone imaging. HER2 status by IHC was 3+ in 9 pts., 2+ in 5 and 1+ in 1. Two women with IHC 2+ disease were FISH+. In the patients considered clinically HER2 positive (IHC 3+ or 2+, FISH+), 64 Cu-DOTA-trastuzumab sensitivity was 75 and 90%, respectively, on Days 1 and 2, compared with 94% for 18 F-FDG. Tumor uptake of 64 Cu-DOTA-trastuzumab was also readily visualized in HER2-negative patients (measured detection sensitivity 90%). There were no false positive findings with 64 Cu-DOTA-trastuzumab. Lesion uptake of 64 Cu-DOTA-trastuzumab was higher in HER2+ than in HER2- patients (SUV max mean ± sem: Day 1 8.9±0.6 vs 4.3±0.2; Day 2 9.9±0.8 vs 5.4±0.3, p &lt; 0.001). Conclusions: 64 Cu-DOTA-trastuzumab PET visualizes HER2 1+, 2+ and 3+ metastatic breast cancer with high sensitivity and specificity. Tumor uptake of 64 Cu-DOTA-trastuzumab-PET in IHC 1+ and 2+ patients implies possible benefit from anti-HER2 therapies for individuals whose cancers are currently considered HER2 negative. Research Support: DOD1024511. Clinical trial information: NCT01093612.
A randomized phase II feasibility study of individualized stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) with DEBDOX beads as a bridge to transplant in hepatocellular carcinoma (HCC).
Authors: Francis W. Nugent, Klaudia Hunter, Chris Molgaard, Amir Qamar, Krishna Gunturu, Keith E. Stuart, Frederic Gordon, Sebastian Flacke
Journal: Journal of Clinical Oncology (2020)

4586 Background: For HCC pts undergoing LT, loco-regional treatment as a "bridge" is standard. The best bridging modality is unclear. SBRT is safe and effective when used in pts with advanced HCC. We prospectively compared SBRT to TACE as a bridge for HCC pts undergoing LT. Methods: From 9/2014-10/2019, 60 pts within Milan Criteria with CTP Class A/B8 cirrhosis were consented. 54 pts were randomized to TACE vs. SBRT. TACE pts (n =30) were scheduled to receive 2 treatments one month apart utilizing DEBDOX beads. TACE pts were hospitalized after each TACE. Pts receiving SBRT (n =24) received a median total dose of 45Gy delivered over 5 fractions using fiducials. Mean liver dose, Veff, and NTCP determined prescription dose. Pts were assessed by using mRECIST criteria at 2 months and every 3 months thereafter until LT or death. Toxicity and QOL were assessed before treatment, during treatment, two weeks post-treatment, and then every three months using the PIQ-6 Pain Impact Questionnaire and the SF-36v2 Health Survey. The 1° endpoint was time to recurrent or residual dz. Secondary endpoints were toxicity, pathologic response, radiologic response, number of subsequent treatments, cost, and QOL. 50 pts are evaluable for review. Results: See table. Conclusions: For early stage HCC patients with CTP Class A/B liver cirrhosis, SBRT appears as effective as TACE at controlling HCC prior to LT, may engender less toxicity, and eliminates the need for hospitalization. A larger multi-center trial is ongoing. Clinical trial information: NCT02182687. [Table: see text]
Clinical and molecular landscape of metastatic colorectal cancer (mCRC) harboring <i>ALK</i>, <i>ROS1</i>, or <i>NTRK</i> 1, 2, 3 (<i>NTRK</i>s) rearrangements.
Authors: Filippo Pietrantonio, Federica Di Nicolantonio, Alexa Betzig Schrock, Jeeyun Lee, Sabine Tejpar, Salvatore Siena, Jason H. Christiansen, Jaclyn Frances Hechtman, Giovanni Fucà, Carlotta Antoniotti, Seung Tae Kim, Bosun Min, Danielle Murphy, Niall C. Tebbutt, Jeffrey S. Ross, Alberto Bardelli, Siraj Mahamed Ali, Alfredo Falcone, Filippo G. De Braud, Chiara Cremolini
Journal: Journal of Clinical Oncology (2017)

589 Background: ALK, ROS1, and NTRKs fusions occur in 0.2-2.4% of CRCs, and represent therapeutic targets, as indicated by promising reports of individual patients treated with tyrosine kinase inhibitors. Clinical and molecular features of mCRCs harboring these fusions have not been elucidated. Methods: mCRC harboring ALK, ROS1 and NTRKs fusions were identified taking advantage of screening programs worldwide (Ignyta STARTRK trials; Foundation Medicine Database; Memorial Sloan Kettering-IMPACT; Australian MAX trial post-hoc analysis). Clinicopathological and molecular characteristics of ALK, ROS1, NTRKs rearranged cases were compared with those of non-rearranged cases, included in Ignyta’s STARTRK trials program. Results: 27 ALK, ROS1 or NTRKs rearranged (including a novel SCYL3-NTRK1 fusion) and 319 not rearranged mCRCs patients were included. Rearrangements were more frequent in older patients (p = 0.024), and tumors that were right-sided (80% vs 30%; p &lt; 0.001), RAS wild-type (93% vs 52%; p &lt; 0.001), MSI-high (48% vs 8%; p &lt; 0.001) and spread more frequently to lymph nodes (46% vs 25%; p = 0.03) and less frequently to the liver (42% vs 66%; p = 0.026). At a median follow-up of 28.5 months, patients bearing rearranged tumors had a shorter overall survival (OS) when compared to non-rearranged (15.6 vs 33.7 mos; HR: 2.17, 95% CI 1.03-4.57; p &lt; 0.001). In the multivariable model including significant prognostic variables (primary site, primary resection, BRAF and MMR status), rearrangements were still associated with shorter OS (HR: 2.78, 95% CI 1.27-6.07; p = 0.011). All of the 4 patients with rearranged tumors evaluable for benefit from anti-EGFRs experienced disease progression as best response. One patient with an MSI-high EML4-ALK rearranged tumor experienced durable response to PD-1 blockade. Conclusions: ALK, ROS1 and NTRKs rearrangements define a new molecular subtype of mCRCs associated with unfavorable prognosis, and specific clinicopathological and molecular features. Since sensitivity to available treatment options, including anti-EGFRs, is very limited, targeted approaches with or without immunotherapy should be investigated in these patients.