Iris Gluck

Lymph node ratio predicts the benefit of post-operative radiotherapy in oral cavity cancer.

BACKGROUND The standard treatment for non-metastatic oral cavity squamous cell carcinoma (OCSCC) is surgical resection followed by post-operative radiotherapy (PORT) with/without chemotherapy in high risk patients. Given the substantial toxicity of PORT we assessed lymph node ratio (LNR) as a predictor of PORT benefit. DESIGN By using the Surveillance, Epidemiology and End Results (SEER) database, we analyzed all node positive OCSCC patients diagnosed between 1988 and 2007 who underwent neck dissection. LNR was categorized into three groups: < 6%, 6-12.5% and > 12.5%. RESULTS In 3091 subjects identified, median survival was 32, 25 and 16 months for LNR Groups 1, 2 and 3, respectively. On multivariate analysis, survival was associated with age, race, grade, tumor size, nodal stage, extra-capsular extension, use of PORT and LNR. When stratified by LNR group, PORT was associated with a survival benefit only in Group 3 (LNR > 12.5%): 2 year survival 25% vs 37%. No benefit to PORT was seen when the LNR ≤ 12.5%: 2 year survival 51% vs 54%. CONCLUSION A low LNR is associated with extended survival in LN positive OCSCC. The survival benefit associated with PORT in this disease appears to be limited to those with a LNR > 12.5%. Validation is required prior to the clinical implementation of our findings.

Association between very young age and adverse characteristics of breast cancer at presentation amongst Israeli women

Background: Up to 4% of breast cancer cases occur in women younger than 35 years. Studies have suggested an association between breast cancer at a young age, poorer outcome, and adverse clinical and pathologic characteristics. It is unclear whether age is an independent prognostic factor. Objectives: To characterize the prognostic significance of young age at diagnosis through comparison of disease characteristics of “less-young” (born between 1958–1962 and aged 37–44 years) and “very-young” (born after 1967 and aged ≤35 years) premenopausal patients. Methods: Consecutive patients with breast cancer born after 1967 treated at Sheba Medical Centre between January, 1999 and October, 2002 were identified and their files reviewed. This cohort was identified as “very-young” and was compared with a group of “less-young” patients. The clinico-pathologic characteristics and survival data were compared. Results: Sixty-one very young and 94 less-young patients were identified. The mean age at diagnosis was 29.9 (range, 23–34 years) and 40.5 years (range, 37–44 years) for the very young and less young patients, respectively (P < 0.0001). Significantly more very young patients had metastatic disease at presentation (20% vs. 3%, respectively, P = 0.0007). The very young patients were more likely to have high grade, endocrine nonresponsive tumors than the less young patients. After controlling for stage and tumor grade, very-young age was not shown to be an independent risk factor for reduced survival. Conclusions: Very young age among Israeli women with breast cancer is associated with higher stage at diagnosis, adverse pathologic characteristics and adverse outcome but is not an independent prognostic factor for survival.

Delayed Sino-nasal Complications of Radiotherapy for Nasopharyngeal Carcinoma

Objective There are only sporadic reports of delayed sino-nasal complications associated with nasopharyngeal carcinoma (NPC) treated with radiotherapy. These include choanal stenosis, osteoradionecrosis, chronic sinusitis, and intranasal synechiae. Most likely, these complications are underestimated as in many institutions nasal endoscopies in NPC patients are not performed routinely. The aim of this study was to identify the onset and incidence of delayed sino-nasal complications in NPC patients and their effect on quality of life (QOL). Study Design Case series with chart review. Setting Tertiary medical center. Subjects and Methods A retrospective chart review was performed on all patients treated for NPC in our institution between 1988 through 2009. The inclusion criteria required at least a 3-year follow-up without recurrence. Included patients were contacted prospectively and asked to fill a SNOT-16 questionnaire. Results Sixty-two patients were included in our review. There were 42 males and 20 females. The average age at onset was 42 years. The AJCC staging for T1, T2, T3, and T4 tumors was 22 (35%), 11 (18%), 18 (29%), and 11 (18%), respectively. Eleven patients (18%) suffered from chronic sinusitis. Nine patients (15%) developed choanal stenosis. Five patients (8%) developed osteoradionecrosis. Two patients suffered from nasal synechiae. Forty-eight patients completed the SNOT-16 questionnaire. Patients with choanal stenosis had the lowest QOL scores out of the cohort. Conclusion The incidence of delayed sino-nasal complications after radiation treatment for NPC is not negligible and should be kept in mind when addressing the quality of life of NPC survivors.

Recurrent metastatic spread to a percutaneous gastrostomy site in a patient with squamous cell carcinoma of the tongue: a case report and review of the literature.

Patients diagnosed with head and neck squamous cell cancer (HNSCC) frequently develop dysphagia and odynophagia owing to advancing disease or as a result of medical interventions. Selected patients diagnosed with advanced HNSCC may require the insertion of a percutaneous endoscopic gastrostomy (PEG) tube as part of their management. During the past 2 decades, there have been increasing reports describing tumor seeding at the PEG exit site, which have caused controversy relating to the technique used in PEG insertion. Although PEG placement is considered a safe procedure for patients with advanced head and neck cancer, the method can lead to tumor seeding, probably from direct traumatic tumor shedding. This report describes a case of tumor implantation at the PEG site in a patient with an advanced SCC of the tongue, with a review of the available literature concerning this rare condition and its possible pathogenesis.

Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012

BackgroundSecond-line treatment options for advanced head and neck squamous cell carcinoma (HNSCC) are limited. The phase Ib KEYNOTE-012 study evaluated the safety and the efficacy of pembrolizumab for the treatment of HNSCC after long-term follow-up.MethodsMulti-centre, non-randomised trial included two HNSCC cohorts (initial and expansion) in which 192 patients were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks (initial cohort; N = 60) or 200 mg every 3 weeks (expansion cohort; N = 132). Co-primary endpoints were safety and overall response rate (ORR; RECIST v1.1; central imaging vendor review).ResultsMedian follow-up was 9 months (range, 0.2–32). Treatment-related adverse events (AEs) of any grade and grade 3/4 occurred in 123 (64%) and 24 (13%) patients, respectively. No deaths were attributed to treatment-related AEs. ORR was 18% (34/192; 95% CI, 13–24%). Median response duration was not reached (range, 2+ to 30+ months); 85% of responses lasted ≥6 months. Overall survival at 12 months was 38%.ConclusionsSome patients received 2 years of treatment and the responses were ongoing for more than 30 months; the durable anti-tumour activity and tolerable safety profile, observed with long-term follow-up, support the use of pembrolizumab as a treatment for recurrent/metastatic HNSCC.

Pseudo pulmonary embolism in cancer patients: a new clinical syndrome.

To characterize the clinical features of oncology patients presenting with shortness of breath mistakenly diagnosed at first with pulmonary emboli, but later found instead to have extrinsic compression of the pulmonary artery or its tributaries by tumor. Medical charts and computed tomography (CT) angiographies of these patients were reviewed retrospectively. In a 7-year period, 11 patients from a single institute were identified. Five patients were excluded as they had a pleural and pericardial effusion that by itself could result in dyspnea. All had varied solid tumors and none had lymphoma. In three of six patients, an increased ratio between right and left ventricle was detected by CT angiography; however, in contradistinction to patients with pulmonary emboli, this was not found to be associated with short survival. The term ‘pseudo pulmonary emboli’ is suggested to describe this phenomenon. Anticoagulant treatment to avoid in-situ pulmonary artery thrombosis may be considered; however, misdiagnosis of pulmonary embolism may delay the appropriate treatment with chemotherapy, biological therapy, and radiotherapy.

Abstract LB-339: Biomarkers predictive of response to pembrolizumab in head and neck cancer (HNSCC)

Background: Biomarkers predictive of response to anti-PD-1 therapy include tumor mutational burden (TMB) and inflammatory biomarkers such as PD-L1 expression and T-cell activated gene expression profile (GEP). This study evaluated relationships between TMB, PD-L1 expression, and GEP and response to pembrolizumab in HNSCC patients in the KEYNOTE (KN)-012 and KN-55 trials. Methods: Data were combined from 261 HNSCC patients in KN-012 (NCT01848834, subsets of B1 [PD-L1 + , ≥1%, modified proportion score or interface pattern, QualTek IHC; n=34] and B2 [n=73] cohorts) and KN-055 (NCT02255097, platinum/cetuximab resistant, n=154) who had TMB data available by whole exome sequencing. Of these, 258 patients had PD-L1 data (PD-L1 IHC using 22C3 pharmDx, CPS readout) and 240 patients had GEP score (RNA analyzed on NanoString nCounter). HPV +/- status was assessed by p16 IHC and WES methods. Statistical testing of relationships between biomarkers and best overall response (BOR) by logistic regression and progression free survival (PFS) by Cox regression was prespecified and performed in a blinded manner. Results: TMB, PD-L1 CPS and GEP were each significantly associated with BOR in the overall population (p - and 80 HPV + patients. TMB and GEP were each highly associated with BOR regardless of HPV - (p=0.0034 and 0.0084) and HPV + (p=0.0446 and 0.0008) status, respectively. PD-L1 CPS showed similar associations with BOR in HPV - (p=0.0649) and HPV + (p=0.0003) patients. TMB showed no correlation with PD-L1 (r = -0.047) and GEP (r = -0.135); whereas PD-L1 CPS and GEP were moderately correlated (r = 0.469), consistent with an interferon-γ induced T-cell activated microenvironment including PD-L1 induction. TMB, PD-L1 CPS and GEP remained significantly predictive for BOR when assessed individually in joint models of TMB and PD-L1, and TMB and GEP (all p - (n=201) and HPV + (n=58) patients identified by p16 IHC, indicating the feasibility of using the WES method. Conclusion: TMB, PD-L1 and T-cell inflamed GEP were independently predictive of response to pembrolizumab in HNSCC patients, in general regardless of HPV status. When used alone or jointly, these biomarkers may have utility in characterizing responses to anti PD-1 therapies and novel cancer regimens in HNSCC. Citation Format: Tanguy Y. Seiwert, Robert Haddad, Joshua Bauml, Jared Weiss, David G. Pfister, Shilpa Gupta, Ranee Mehra, Iris Gluck, Hyunseok Kang, Francis Worden, J. Paul Eder, Makoto Tahara, Barbara Burtness, Stephen V. Liu, Andrea Webber, Lingkang Huang, Robin Mogg, Razvan Cristescu, Jonathan Cheng, Laura Q. Chow. Biomarkers predictive of response to pembrolizumab in head and neck cancer (HNSCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-339.

The Effect of Head and Neck Radiotherapy on Blood Pressure and Orthostatic Hypotension in Patients With Head and Neck Tumors

BACKGROUND Radiotherapy (RT) plays a key role in the management of head and neck cancer (HNC), especially in locally advanced disease. Patients undergoing head and neck RT, especially elderly ones, are suffering from low and labile blood pressure (BP) during the treatment. They complain of weakness and fatigue and are prone to recurrent falls. The aim of this study was to characterize BP changes during RT period. METHODS Patients with HNC, receiving radiation to the neck, were recruited from Sheba medical center RT unit. Office BP, orthostatic measurements, 24-hour ambulatory BP monitoring, body weight, and metabolic parameters were measured at baseline after 30 days and after 90 days from beginning of therapy. RESULTS Nineteen patients (17 males), 64 ± 12 years old were recruited. Nine hypertensive patients continued their antihypertensive treatment during the study. Office systolic BP and diastolic BP decreased significantly after 30 days (128 ± 4/80 ± 3 to 122 ± 3/74 ± 3 mm Hg; P < 0.05). Average 24-hour BP values after 30 days of RT decreased from 130 ± 3/76 ± 2 to 123 ± 3/71 ± 2 mm Hg; P < 0.05. A similar trend was observed for day and night BP levels. Decrease in office and ambulatory BP was sustained for several months after RT completion. No orthostasis was observed during the study period. Patient lost weight significantly during the study period. However, BP changes were independent of weight loss. CONCLUSION There is a significant and sustained BP reduction after head and neck RT, without orthostatic changes. Clinicians should be aware of this phenomenon and consider treatment adaption accordingly.