Citations

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

Abstract Background: FGFR dysregulation is observed in multiple cancers and targeting FGFR is an emerging therapeutic strategy with FDA approved treatments in bladder and cholangiocarcinoma. Here we examined the prevalence of FGFR mutations, fusions, and high-level amplifications in breast cancer, stratified by receptor subtype and local/metastatic status, in both Foundation Medicine (FM) and institutional Mayo Clinic (MC) cohorts. Methods: For the FM cohort, comprehensive genomic profiling (CGP) examining at least 324 genes for all classes of alterations, including FGFR1-4 was carried out for 32,048 breast cancers during the course of routine clinical care in a Clinical Laboratory Improvement Amendments (CLIA)-certified lab (Foundation Medicine Inc., Cambridge, MA, USA). Tumor mutational burden (TMB) was determined on up to 1.1 Mb, microsatellite instability high (MSI-High) was determined on up to 114 loci and predicted ancestry from >10,000 SNPs. Estrogen receptor (ER) and HER2 status were available for a subset of FM samples. Additionally, 131 patients with metastatic breast cancer from a subset of patients at three Mayo Clinic sites (MC cohort) with clinical characteristics and cancer-panel DNA sequencing data from a CLIA-certified lab (Tempus, Chicago, IL) were included. Results: In the FM cohort, the prevalence of FGFR1-4 high-level amplification (CN≥10) was 10.1%, while mutations (1.5%) and fusions (0.72%) were rare. Most amplifications occurred in FGFR1 (9.2%); most fusions and mutations occurred in FGFR2 (0.46%, 0.77%). FGFR alteration prevalence was highest in ER+/HER2- subtype (14.4%) and lowest in HER2+ disease (7.7%). FGFR alterations were more common in IDC (11.7%) than ILC (7.7%), p<3E-08. FGFR alterations were more prevalent in the metastatic setting relative to breast-biopsied disease (13.6% v 10.1%; OR = 1.4; p=2E-17), especially in the HER2+ (OR =1.9, p=0.004) and ER-/HER2- (OR = 1.9, p = 0.05) disease; no enrichment was seen in the ER+/HER2- metastases (OR =1.0, p = 1). FGFR amplifications were observed at a higher prevalence in patients with predicted East Asian ancestry, relative to patients with European ancestry (12.1% v 10.0%; p = 0.03). Overall, the most common activating mutations in FGFR were FGFR2 N549K (n=85), FGFR1 N546K (n=78), FGFR4 V510M (n=28), FGFR2 K659E (n=28), FGFR4 V510L (n=20), and FGFR2 Y375C (n=15). The most common recurrent fusions were FGFR3:TACC3 (n=36), FGFR2:TACC2 (n=17), FGFR1:TACC1 (n=9), FGFR1:BAG4 (n=6), and FGFR2:ATE1 (n=5). In patients with FGFR amplifications, the most frequently co-occurring alterations were ZNF703 (78.4%), TP53 (51.5%), CCND1 (36.1%), FGF3/4/19 (32.9 - 34.4%), PIK3CA (30.7%), MYC (29.6%), ESR1 (17.2%), EMSY (16.3%), and PTEN (10.6%). Significant co-occurrence was observed for a number of genes including FGF3/4/19, CDK4, and CDK8 (all OR>2, p<1E-07); mutual exclusivity was observed with PIK3R1, BRCA1, and BRCA2 (all OR <0.5, p<4E-13), among other genes. In the 131 metastatic tumors from MC, the prevalence of FGFR1-4 high-level amplifications was 19.8% [FGFR1 (12.4%), FGFR2 (7.4%), and FGFR3 (0.8%)]. The prevalence of high-level FGFR amplifications did not differ by clinical subtypes: HR-/HER2- (7/31), HR+/HER2- (15/79), and HER2+ (2/11), p=0.68. Conclusions: High-level FGFR amplifications are observed in >11% of breast cancers, especially the ER+/HER2- subtype, while mutations/fusions are rare. These data support the ongoing studies evaluating targeted therapies for FGFR amplified ER + breast cancer. Correlations with clinical information (MC cohort) and associations with actionable alterations are ongoing and may inform potential combination strategies. Citation Format: Karthik V Giridhar, Ethan S Sokol, Peter T Vedell, Jason P Sinnwell, Aakash Desai, Tufia C Haddad, Ciara C O’Sullivan, Roberto A Leon-Ferre, Siddhartha Yadav, Kostandinos Sideras, Brenda Ernst, Minetta C Liu, Abe Eyman Casey, Xiaojia Tang, Zoe Fleischmann, Karthikeyan Murugesan, Krishna R Kalari, Matthew P Goetz. The frequency and somatic mutation landscape of Fibroblast growth factor receptor (FGFR) alterations in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-08-02.

BACKGROUND Hirayama disease (HD), also known as juvenile spinal muscular atrophy, is a rare condition in which flexion of the cervical neck causes compression and ischemic changes to the anterior horns of the spinal cord. Here the authors presented the first reported case of HD in North America that was successfully treated via surgical intervention. OBSERVATIONS The patient was a 15-year boy with insidious onset upper limb weakness and atrophy. His findings were a classic presentation of HD although his complex history and relative rarity of the disease caused him to remain undiagnosed for months. After conservative management via cervical collar failed, the patient was successfully treated via C5-C7 anterior cervical discectomy and fusion. The patient’s symptoms stabilized by the 3-month follow-up. LESSONS The diagnosis of HD is easy to miss because of the lack of reporting and widespread knowledge of this condition in North America. Thus, when presented with a case of insidious onset limb weakness in a juvenile patient, HD should be placed on the differential list and verified with cervical flexion magnetic resonance imaging. Additionally, surgical intervention should be considered a safe and effective option for HD when conservative methods have failed.

PURPOSEAn ASCO provisional clinical opinion offers timely clinical direction to ASCO's membership following publication or presentation of potentially practice-changing data from major studies. This provisional clinical opinion addresses the appropriate use of tumor genomic testing in patients with metastatic or advanced solid tumors.CLINICAL CONTEXTAn increasing number of therapies are approved to treat cancers harboring specific genomic biomarkers. However, there is a lack of clarity as to when tumor genomic sequencing should be ordered, what type of assays should be performed, and how to interpret the results for treatment selection.PROVISIONAL CLINICAL OPINIONPatients with metastatic or advanced cancer should undergo genomic sequencing in a certified laboratory if the presence of one or more specific genomic alterations has regulatory approval as biomarkers to guide the use of or exclusion from certain treatments for their disease. Multigene panel–based assays should be used if more than one biomarker-linked therapy is approved for the patient's disease. Site-agnostic approvals for any cancer with a high tumor mutation burden, mismatch repair deficiency, or neurotrophic tyrosine receptor kinase ( NTRK) fusions provide a rationale for genomic testing for all solid tumors. Multigene testing may also assist in treatment selection by identifying additional targets when there are few or no genotype-based therapy approvals for the patient's disease. For treatment planning, the clinician should consider the functional impact of the targeted alteration and expected efficacy of genomic biomarker–linked options relative to other approved or investigational treatments. Additional information is available at www.asco.org/assays-and-predictive-markers-guidelines .

TPS598 Background: CG0070 is a serotype 5 adenovirus engineered to express GM-CSF and replicate in cells with mutated or deficient RB, with response rates (RR) of approximately 45% observed in patients with recurrent NMIBC after BCG (J Urol. 2012;188:2391–7; Urol Oncol. 2018;36(10):440–7). This single arm phase 3 study (NCT04452591) was launched to confirm the clinical activity of CG0070 in patients with BCG Unresponsive NMIBC. Methods: 110 patients with BCG-unresponsive CIS with or without concurrent Ta or T1 disease will be treated with intravesical (IVe) CG0070 at a dose of 1x1012 vp. CG0070 will be administered as follows: induction weekly x 6 followed by weekly x 3 maintenance instillations at months 3, 6, 9, 12, and 18. Patients with persistent CIS or HG Ta at 3 months (m) may receive re-induction with weekly x 6 CG0070. Assessment of response will include q 3 m cystoscopy with biopsy of areas suspicious for disease, urine cytology, CTU/MRU, and mandatory bladder mapping at 12 m. Detection of high grade disease within the bladder will be enumerated as recurrence or non-response. The primary endpoint of the study is CR at any time on study as assessed by biopsy (directed to cystoscopic abnormalities and mandatory mapping at 12 m), urine cytology, and radiography, as above. Secondary endpoints include CR at 12 m, duration of response, progression free survival, cystectomy free survival and safety. Correlative assessments include changes in the tumor immune microenvironment, systemic immune induction as reflected in the peripheral blood and urine, as well as viral replication and transgene expression. Baseline expression of coxsackie adenovirus receptor, E2F transcription factor as well as anti-adenovirus antibody titer will be correlated with tumor response. Study enrollment globally is ongoing including in North America, Taiwan, Japan, and South Korea. Refs. Burke JM, Lamm DL, Meng MV, Nemunaitis JJ, Stephenson JJ, Arseneau JC, Aimi J, Lerner S, Yeung AW, Kazarian T, Maslyar DJ, McKiernan JM. A first in human phase 1 study of CG0070, a GM-CSF expressing oncolytic adenovirus, for the treatment of nonmuscle invasive bladder cancer. Clinical trial information: NCT04452591.

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) provide recommendations for the evaluation, diagnosis, and management of patients with MDS based on a review of clinical evidence that has led to important advances in treatment or has yielded new information on biologic factors that may have prognostic significance in MDS. The multidisciplinary panel of MDS experts meets on an annual basis to update the recommendations. These NCCN Guidelines Insights focus on some of the updates for the 2022 version of the NCCN Guidelines, which include treatment recommendations both for lower-risk and higher-risk MDS, emerging therapies, supportive care recommendations, and genetic familial high-risk assessment for hereditary myeloid malignancy predisposition syndromes.

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.

Objective: To analyze insulin delivery and glycemic metrics throughout the menstrual cycle for women with type 1 diabetes using closed loop control (CLC) insulin delivery. Methods: Menstruating women using a CLC system in a clinical trial were invited to record their menstrual cycles through a cycle-tracking application. Sixteen participants provided data for this secondary analysis over three or more complete cycles. Insulin delivery and continuous glucose monitoring (CGM) data were analyzed in relation to reported cycle phases. Results: Insulin delivery and CGM metrics remained consistent during cycle phases. Intraparticipant variability of CGM metrics and weight-based insulin delivery did not change through cycle phases. Conclusions: For this sample of menstruating women with type 1 diabetes using a CLC system, insulin delivery and glycemic metrics remained stable throughout menstrual cycle phases. Additional studies in this population are needed, particularly among women who report variable glycemic control during their cycles. Trial Registration: NCT03591354.

The NCCN Guidelines for Kidney Cancer focus on the screening, diagnosis, staging, treatment, and management of renal cell carcinoma (RCC). Patients with relapsed or stage IV RCC typically undergo surgery and/or receive systemic therapy. Tumor histology and risk stratification of patients is important in therapy selection. The NCCN Guidelines for Kidney Cancer stratify treatment recommendations by histology; recommendations for first-line treatment of ccRCC are also stratified by risk group. To further guide management of advanced RCC, the NCCN Kidney Cancer Panel has categorized all systemic kidney cancer therapy regimens as “Preferred,” “Other Recommended Regimens,” or “Useful in Certain Circumstances.” This categorization provides guidance on treatment selection by considering the efficacy, safety, evidence, and other factors that play a role in treatment selection. These factors include pre-existing comorbidities, nature of the disease, and in some cases consideration of access to agents. This article summarizes surgical and systemic therapy recommendations for patients with relapsed or stage IV RCC.