Tumor infiltrating lymphocyte stratification of prognostic staging of early-stage triple negative breast cancer

The importance of integrating biomarkers into the TNM staging has been emphasized in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging system. In a pooled analysis of 2148 TNBC-patients in the adjuvant setting, TILs are found to strongly up and downstage traditional pathological-staging in the Pathological and Clinical Prognostic Stage Groups from the AJJC 8th edition Cancer Staging System. This suggest that clinical and research studies on TNBC should take TILs into account in addition to stage, as for example patients with stage II TNBC and high TILs have a better outcome than patients with stage I and low TILs.

Evolution in Sinonasal Mucosal Melanoma Management

Sinonasal mucosal melanoma is a rare and aggressive cancer with poor prognosis. Surgical resection with clear margins, when possible, remains the treatment of choice. Radiation therapy is generally used in the adjuvant setting with improved rates of local control following complete resection. Traditional chemotherapeutic agents do not improve the rates of locoregional control or survival. Immunotherapy has been used with some responders but with overall relatively poor outcomes. These outcomes highlight the need for new agents and more prospective trials in this space. We provide a unique case report of a patient with an advanced sinonasal mucosal melanoma and an overview of the recent literature pertaining to the management of this disease.

O-OGC09 PD-1 inhibitors in Oesophageal Cancer: A systematic review of the oncological outcomes associated with PD-1 blockade and the evolving therapeutic landscape

Background Patients with oesophageal or gastro-oesophageal junction (GOJ) cancer that fail to respond to chemoradiotherapy have a poor clinical prognosis. Recent clinical trials have investigated the use of immune checkpoint inhibitors in these patients. The use of programmed cell death protein 1 (PD-1) inhibitors have emerged as exciting therapeutic options in other solid tumors, such as non-small cell lung cancer, renal cell carcinoma and melanoma. We assessed the efficacy and safety of PD-1 inhibitors in oesophageal and GOJ cancers. Methods This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive electronic literature search from the EMBASE, Pubmed, Scopus, MEDLINE and Google Scholar databases was conducted up to April 1st 2021. Results This review identified nine eligible studies reporting outcomes of 2149 patients treated with PD-1 blockade compared with 1244 patients treated with either a placebo or the standard regimen of chemotherapy for oesophageal and GOJ cancer. Clinically significant improvements in median overall survival have been demonstrated in advanced and metastatic oesophageal and GOJ cancer while maintaining acceptable safety profiles. Promising survival data has also recently emerged from PD-1 blockade in the adjuvant setting. Conclusions PD-1 blockade in oesophageal and GOJ cancer has delivered impressive survival benefit whilst remaining well tolerated. Its use in the adjuvant setting may further advance our treatment options for this difficult-to-treat tumour, and more advancements in the immunotherapy landscape are highly anticipated. However, further characterization of the PD-1/PD-L1 pathway is required to optimise patient selection.

RADT-29. CHARACTERISTICS OF PATIENTS WITH MENINGIOMA WHO DEVELOPED SIGNIFICANT EDEMA REQUIRING STEROIDS AFTER GAMMA KNIFE RADIOSURGERY

Gamma Knife stereotactic radiosurgery (GK-SRS) is an effective treatment of meningioma in the definitive and adjuvant setting. While SRS is generally safe, some patients develop significant post-treatment edema leading to seizures and neurological deficits requiring medical intervention. This study identifies risk factors associated with the development of significant edema after SRS. Between 2014 and 2020, 126 patients with 182 WHO grade I-III meningiomas were treated with GK-SRS at our institution. We retrospectively identified a subset of patients with clinically significant post-treatment edema on MRI and documented steroid use. Clinical and treatment parameters such as treatment intent, dose, tumor location, and tumor volume were collected. The median follow-up was 34 months. A total of 6 patients (4 females and 2 males, median age 60.5) developed symptomatic edema, including 4 of 71 patients treated in the definitive setting, 1 of 16 patient in the postoperative adjuvant setting, and 1 of 39 patient in the salvage setting. 2 patients had convexity meningioma, 3 patients had parasagittal meningioma, and 2 patients had skull base meningioma. The median onset of symptomatic edema after SRS was 5 months (range: 2-5months); the median duration of steroid use was 1.5 months (range: 0.5-3months). Mild headache and vision changes were reported in 2 patients. 4 patients developed seizures and required hospital admission. 1 patient died of cardiac arrest during admission. The remainder of patients were symptom-free following discontinuation of steroids and required no surgical intervention. The median tumor volume was 3.625cc (range: 2.74-12.15cc). All patients received single-fraction SRS with a median dose of 16Gy (range: 16-20Gy). 2 patients had received prior fractionated cranial radiation. A subset of meningioma patients treated with SRS can develop significant post-treatment edema requiring intervention. This small series showed that the risk of symptomatic edema with SRS is low, and most symptoms are transient.

CTNI-26. PHASE 2 STUDY OF DIANHYDROGALACTITOL (VAL-083) IN PATIENTS WITH MGMT-UNMETHYLATED, BEVACIZUMAB-NAÏVE GLIOBLASTOMA IN THE RECURRENT AND ADJUVANT SETTING

Current standard-of-care for glioblastoma (GBM) includes surgery followed by concurrent therapy with radiation and temozolomide (TMZ) followed by adjuvant TMZ. Almost all GBM patients experience recurrent/progressive disease despite upfront standard-of-care treatment, with a median survival of 3-9 months after recurrence. Unmethylated promoter for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for TMZ-resistance and is correlated with poor patient prognosis. VAL-083 is a bi-functional DNA-targeting agent which rapidly induces interstrand DNA cross-links at N7-guanine inducing double-strand breaks causing cell death and acts independently of MGMT DNA repair. This trial is an open-label two-arm biomarker-driven phase 2 clinical trial in MGMT-unmethylated, bevacizumab-naïve GBM patients with either recurrent (Group 1) or newly diagnosed GBM requiring adjuvant therapy after chemo-irradiation with temozolomide (Group 2). Patients receive VAL-083 IV at 30 or 40 mg/m2/d on days 1, 2, and 3 of a 21-day cycle. The primary objective of this study is to determine the effect of VAL-083 on median overall survival (mOS) in MGMT-unmethylated recurrent GBM patients (Group 1); and progression-free survival (PFS) in newly diagnosed GBM patients requiring adjuvant therapy after chemo-irradiation with temozolomide (Group 2), compared to historical controls in both groups. Tumor response is assessed by MRI every 42 days, using RANO criteria. The initial starting dose in this study was 40 mg/m2/d on days 1, 2, and 3 of a 21-day cycle, which was subsequently reduced to 30 mg/m2/d to improve tolerance due to myelosuppression. As of May 2021, Group 1 (Recurrent GBM) is fully enrolled: 35 evaluable patients have received 40 mg/m2/d and 48 evaluable patients have received 30 mg/m2/d VAL-083. In the adjuvant setting (Group 2), 35 evaluable patients have been enrolled (30 mg/m2/day). Enrollment, safety data and efficacy updates will be presented at the meeting. Clinicaltrials.gov identifier: NCT02717962.

308 Transcriptomic analysis of melanoma patients in adjuvant setting treated with anti PD1 therapy: real life study

BackgroundAdjuvant treatment of melanoma patients with immune-checkpoint inhibition (ICI) significantly improved relapse-free survival (RFS).1 In the phase 3 keynote-054 trial showed that pembrolizumab (anti-PD1) administration in adjuvant setting provided a longer RFS (59,8%) than the placebo group (41,4%) at a 3.5-year median follow-up.2 Moreover, 4 years RFS results from the phase 3 checkmate 238 trial, showed a superior efficacy of nivolumab versus ipilimumab in patients with resected AJCC-7 stage III or IV melanoma. RFS rate was of 58% in the nivolumab arm and 45% in the ipilimumab arm.3 Although treatment with ICIs has improved the RFS of melanoma patients in adjuvant setting, there is still a large proportion of patients who do not respond to the treatment and then relapse. The aim of this study was to investigate the molecular mechanisms underlying resistance to anti-PD1 treatment in the adjuvant setting.MethodsFrom December 2018 to July 2020, n. 121 melanoma patients in stage III or IV NED were treated with anti-PD1s as adjuvant (minimum follow up of 12 months, range 12–30 months). These patients received nivolumab (n=95) or pembrolizumab (n=26). Distant and local metastases was observed in 33 (27%) and 7 (6%) patients, respectively (patients baseline characteristics are listed in table1). Gene expression profiles, using NanoString IO 360 panel, were performed from peripheral blood mononuclear cell (PBMCs), collected retrospectively, from n.73 patients (of which n.26 had relapse). All patients have appropriately signed informed consent. Statistical analysis was performed via Bonferroni correction, P< 0.05 was considered statistically significant for median stratification.ResultsAt a minimum follow-up of 12 months, the 12-month rate of Relapse-free survival was 72%, confirming the data reported by checkmate 238 trial. In the transcriptomic analysis we observed that in patients with local-regional metastases there was a higher expression of ITGA2 (p<0.05), a gene that promotes malignant tumor aggression by up-regulating PD-L1 expression through STAT3 pathway and the downregulation of DUSP1 (p<0.05) that is linked in promotion of angiogenesis, invasion and metastasis. Moreover, in male group we found a higher expression of HLA-DQB1 and HLA-DQA1 which belonged to HLA class II beta chains.Abstract 308 Table 1ConclusionsIn this preliminary report we found that RFS 1-yr rate is similar to checkmate 238 study, and that patients with local metastasis have a higher expression of genes related to promote PDL1 levels. Further investigations are needed to get additional information.AcknowledgementsThe study was supported by the Institutional Project ”Ricerca Corrente” of Istituto Nazionale Tumori IRCCS Fondazione ”G. Pascale” of Napoli, Italy.ReferencesWeber J, Mandala M, Del Vecchio M, et al, CheckMate 238 Collaborators. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med 2017 November 9;377(19):1824–1835.Eggermont AMM, Blank CU, Mandalà M, et al. EORTC melanoma group. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol 2021 May;22(5):643–654.Ascierto PA, Del Vecchio M, Mandalá M, et al. Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial. Lancet Oncol 2020 November;21(11):1465–1477.Ethics ApprovalThe study was approved by internal ethics board of the Istituto Nazionale Tumori IRCCS Fondazione ”G. Pascale” of Napoli Italy, approval number of registry 33/17 OSS.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

ASCO 2021—selection of personal highlights in early stage non-small cell lung cancer

SummaryThis article intends to summarize personal non-small cell lung cancer (NSCLC) highlights of the virtual ASCO 2021 meeting. Immunotherapy is now a mainstay of advanced stage NSCLC treatment and there are several ongoing studies investigating the role of immunotherapy in early stage NSCLC. At ASCO 2021 the first data on atezolizumab in the adjuvant setting were presented and give a positive signal that immunotherapy will also become an option for patient in early stage NSCLC. Furthermore, overall survival (OS) updates of two studies investigating the effects of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the adjuvant setting of EGFR-mutated NSCLC patients were presented. In conclusion ASCO 2021 provided the lung cancer community with inspiring new data especial in early stages and challenges the community with integration of these data into our daily clinical routine.

Radiotherapy in the Adjuvant and Advanced Setting of CSCC

Introduction: The use of radiotherapy for cutaneous squamous cell carcinoma (CSCC) has solid historical roots. It is used with patients who are not suitable for surgery, patients with high-risk histological features in the adjuvant setting, and in palliative care. Objectives: The aim of this article is to summarize and provide a radiation therapy overview on the indications, effectiveness, and potential adverse events of radiotherapy in the adjuvant and advanced setting of CSCC. Methods: We performed a comprehensive literature review on PubMed, adopted as our biomedical literature database. Articles were selected based on their date of publication (in the last 30 years) and relevance. Results: Radiotherapy (RT) can safely be used to manage non-surgical patients and high-risk patients in the advanced CSCC setting. The remarkable progress of delivery techniques has greatly improved the effectiveness and toxicity profile of RT treatments. From 2D techniques to intensity modulated radiation therapy (IMRT), and brachytherapy, all RT techniques have greatly advanced. To improve acute and chronic side effects, deeper care has been used. As regards CSCC, several dose fractionations and schedules have been suggested, in line with the patient’s age and medical conditions. Conclusions: RT is a fundamental and constantly evolving therapeutic option in the treatment of CSCC, to minimize the risk of recurrence and metastases in the adjuvant setting and in the exclusive treatment for non-surgical patients. Patients’ selection is crucial, together with and a collaborative team working approach among the specialists involved in disease management in the perspective of the best multidisciplinary assessment.

PD-1 inhibitors in esophageal cancer: a systematic review of the oncological outcomes associated with PD-1 blockade and the evolving therapeutic paradigm

Patients with esophageal or gastroesophageal junction (GEJ) cancer who fail to respond to chemoradiotherapy have a poor clinical prognosis. Recent clinical trials have investigated the use of immune checkpoint inhibitors in these patients. The use of programmed cell death protein 1 (PD-1) inhibitors has emerged as exciting therapeutic options in the curative and palliative setting of other solid tumors. We assessed the efficacy and safety of PD-1 inhibitors in esophageal and GEJ cancers. This systematic review was performed in accordance with the PRISMA guidelines. A comprehensive electronic literature search from the EMBASE, Pubmed, Scopus, MEDLINE, and Google Scholar databases was conducted up to 25 July 2021. This review identified 11 eligible studies reporting outcomes of 3451 patients treated with PD-1 blockade compared with 2286 patients treated with either a placebo or the standard regimen of chemotherapy. Clinically significant improvements in median overall survival have been demonstrated in advanced and metastatic esophageal and GEJ cancer while maintaining acceptable safety profiles. Promising survival data have also recently emerged from PD-1 blockade in the adjuvant setting. PD-1 blockade in esophageal and GEJ cancer has delivered impressive survival benefit while remaining well tolerated. Its use in the adjuvant setting will further advance treatment options, and more advancements in this area of therapy are highly anticipated. However, further characterization of the PD-1/programmed death ligand-1 pathway and elucidation of biomarkers to predict response are required to optimize patient selection.