Couple-based communication intervention for head and neck cancer: a randomized pilot trial.

OBJECTIVE: To test feasibility and preliminary efficacy of a couple-based supportive communication (CSC) intervention for head and neck cancer (HNC) delivered during patients' oncology treatment. METHODS: Twenty couples were randomly assigned to either a four-session CSC or a treatment-as-usual (TAU) condition. The CSC intervention primarily focused on increasing couple emotional disclosure, supportive listening, and social support. Patients and partners completed measures of individual and relationship functioning at baseline, post-intervention, and 6-month follow-up. RESULTS: Ninety-eight percent of CSC sessions were completed and couples reported high levels of satisfaction with the intervention. Between-group effect sizes indicated that patients and partners in CSC reported improvements in individual and relationship functioning, relative to those in the TAU condition. CONCLUSIONS: A couple-based communication intervention delivered during oncology treatment is feasible and acceptable in the context of HNC and may lead to improvements in individual and relationship functioning. Preliminary efficacy results are interpreted in the context of social-cognitive processing and intimacy theories. TRIAL REGISTRATION: The trial was registered on www.clinicaltrials.gov (NCT01785576) first posted on February 7, 2013.

Measuring financial toxicity as a clinically relevant patient-reported outcome: The validation of the COmprehensive Score for financial Toxicity (COST).

BACKGROUND: Cancer and its treatment lead to increased financial distress for patients. To the authors' knowledge, to date, no standardized patient-reported outcome measure has been validated to assess this distress. METHODS: Patients with AJCC Stage IV solid tumors receiving chemotherapy for at least 2 months were recruited. Financial toxicity was measured by the COmprehensive Score for financial Toxicity (COST) measure. The authors collected data regarding patient characteristics, clinical trial participation, health care use, willingness to discuss costs, psychological distress (Brief Profile of Mood States [POMS]), and health-related quality of life (HRQOL) as measured by the Functional Assessment of Cancer Therapy: General (FACT-G) and the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires. Test-retest reliability, internal consistency, and validity of the COST measure were assessed using standard-scale construction techniques. Associations between the resulting factors and other variables were assessed using multivariable analyses. RESULTS: A total of 375 patients with advanced cancer were approached, 233 of whom (62.1%) agreed to participate. The COST measure demonstrated high internal consistency and test-retest reliability. Factor analyses revealed a coherent, single, latent variable (financial toxicity). COST values were found to be correlated with income (correlation coefficient [r] = 0.28; P<.001), psychosocial distress (r = -0.26; P<.001), and HRQOL, as measured by the FACT-G (r = 0.42; P<.001) and by the EORTC QOL instruments (r = 0.33; P<.001). Independent factors found to be associated with financial toxicity were race (P = .04), employment status (P<.001), income (P = .003), number of inpatient admissions (P = .01), and psychological distress (P = .003). Willingness to discuss costs was not found to be associated with the degree of financial distress (P = .49). CONCLUSIONS: The COST measure demonstrated reliability and validity in measuring financial toxicity. Its correlation with HRQOL indicates that financial toxicity is a clinically relevant patient-centered outcome. Cancer 2017;123:476-484. © 2016 American Cancer Society.

A Contemporary Analysis of Surgical Trends in the Treatment of Squamous Cell Carcinoma of the Oropharynx from 1998 to 2012: A Report from the National Cancer Database.

BACKGROUND: This study examined surgical trends for oropharynx squamous cell carcinoma (OPC) from 1998 to 2012, with a post-2009 focus coinciding with the Food and Drug Administration (FDA) approval of transoral robotic surgery (TORS). METHODS: Using the National Cancer Data Base, the study analyzed 84,449 patients with stage I-IVB OPC. χ (2) tests and logistic regression models were used to examine surgical trends. RESULTS: The use of surgery decreased from 41.4 % in 1998 to 30.4 % in 2009 (p < 0.001). The surgical trends reversed and in 2012 increased to 34.8 % (p < 0.001). There was much variation in surgery in 2012 between American Joint Committee on Cancer stages, with 80.2 % of stage I patients receiving surgery compared with 54.0 % of stage II patients, 36.8 % of stage III patients, and 28.5 % of stage IV patients (p < 0.001). Black patients with high socioeconomic status (SES) showed lower use of surgery (25.3 %) compared to low SES white (32.3 %) and low SES Hispanic patients (27.3 %) (p < 0.001). The highest surgical rates were noted in the West North Central region and lowest rates were observed in the New England and South Atlantic regions. Between 2009 and 2012, independent predictors of surgical treatment included young age, female gender, white or Hispanic race, high SES, private insurance, academic hospitals, hospitals in the West North Central region, residence more than 75 miles from the hospital, increasing comorbidities, stage I disease, and tonsil origin (all p < 0.05). CONCLUSION: Since FDA approval of TORS in 2009, surgical rates have increased with multiple socioeconomic and regional factors affecting patient selection. This study provides a basis for further investigation into factors involved in decision making for OPC patients.

Cixutumumab and temsirolimus for patients with bone and soft-tissue sarcoma: a multicentre, open-label, phase 2 trial.

BACKGROUND: Preclinical studies have shown synergistic antitumour activity by inhibition of insulin-like growth factor-1 receptor (IGF-1R) and mTOR. The expression of IGF-1R seems to be crucial for this effect. We investigated the safety and efficacy of the combination of the IGF-1R antibody cixutumumab and the mTOR inhibitor temsirolimus in patients with chemotherapy-refractory bone and soft-tissue sarcomas according to IGF-1R expression by immunohistochemistry. METHODS: We undertook a multicentre, open-label, phase 2 study in 19 cancer centres in the USA. Patients aged at least 16 years with a histologically confirmed diagnosis of bone or soft-tissue sarcoma were allocated on the basis of IGF-1R expression by immunohistochemistry to one of three treatment groups: IGF-1R-positive soft-tissue sarcoma (group A), IGF-1R-positive bone sarcomas (group B), or IGF-1R-negative bone and soft-tissue sarcoma (group C). Patients received weekly treatment with cixutumumab (6 mg/kg, intravenous) and temsirolimus (25 mg, intravenous flat dose) in 6-week cycles. A Simon optimal two-stage design was used for every arm. The primary endpoint was progression-free survival (PFS) at 12 weeks by intention-to-treat analysis in the first 54 patients assigned to every treatment arm. Although patients still remain on treatment, this trial has completed enrolment and this represents the final analysis. This study is registered with ClinicalTrials.gov, number NCT01016015. FINDINGS: Between Nov 18, 2009, and April 11, 2012, 388 patients were screened for IGF-1R expression and 54 were assigned to each arm. 17 of 54 patients in the IGF-1R-positive soft-tissue sarcoma group (31%; one-sided 95% CI lower bound 21%; two-sided 90% CI 21-43), 19 of 54 in IGF-1R-positive bone sarcoma group (35%; one-sided 95% CI lower bound 24%; two-sided 90% CI 24-47), and 21 of 54 in the IGF-1R-negative group (39%, one-sided 95% CI lower bound 28%; two-sided 90% CI 28-51) were progression free at 12 weeks. On April 6, 2011, the protocol was amended to include three additional patients in the IGF-1R-positive soft-tissue sarcoma group (total of 57 patients) and nine more in the IGF-1R-negative group (total of 63 patients). There were 2546 adverse events reported during the study, 214 (8%) of which were grade 3-4. The most common grade 3-4 toxicities in the 174 treated patients were anaemia in 16 (9%) patients, hyperglycaemia in 18 (10%), hypophosphataemia in 16 (9%), lymphopenia in 25 (14%), oral mucositis in 19 (11%), and thrombocytopenia in 19 (11%). INTERPRETATION: The combination of cixutumumab and temsirolimus shows clinical activity in patients with sarcoma and forms a basis for future trials. However, IGF-1R expression by immunohistochemistry is not predictive of clinical outcome after treatment with this combination. FUNDING: National Cancer Institute and CycleforSurvival Fund, Memorial Sloan-Kettering Cancer Center.

Adult-onset multifocal kaposiform hemangioendothelioma in the bone marrow, lung, liver, and brain: a case report.

Kaposiform hemangioendothelioma (KHE), a rare form of vascular neoplasm, is typically seen in children. In this paper, we report a unique case of KHE replacing bone marrow tissue mimicking myeloproliferative neoplasm with additional involvement in the lung, liver, and brain in a 60-year-old Caucasian woman. The patient was initially seen in the hematology department for the chief complaint of epigastric pain and anemia. Abdominal magnetic resonance imaging (MRI) revealed mild splenomegaly with iron deposition secondary to extramedullary hematopoiesis. Additional workup was inconclusive. Subsequent bone marrow and lung biopsies eventually revealed bone marrow with extensive grade 3 fibrosis and multiple foci of low-grade vasoformative neoplasm in the lung suggestive of KHE. Although rare, KHE can present as an aggressive disease with indolent behavior in adults and can be distinguished from other vascular malignancies based on histopathology and imaging findings.

Bilateral areolar leiomyomas in a patient undergoing BRAF inhibition therapy for melanoma.

BRAF inhibition therapy, used to treat melanomas with BRAF mutations, is associated with both neoplastic and non-neoplastic cutaneous side effects including squamous cell carcinomas, warty dyskeratomas, verrucous keratoses, photosensitivity and widespread eruptions that present histopathologically as acantholytic dyskeratosis. We report a case of a patient undergoing BRAF inhibition therapy for disseminated melanoma with a V600E mutation who developed bilateral areolar leiomyomas, one of which was biopsied and the other of which resolved after discontinuation of vemurafenib therapy. To our knowledge, this is the first reported case of a mesenchymal neoplasm developing in association with BRAF inhibition therapy.

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma.

CONTEXT.­: Pembrolizumab is used in patients with metastatic head and neck squamous cell carcinoma contingent upon the programmed death ligand-1 (PD-L1) combined positive score (CPS). OBJECTIVE.­: To compare PD-L1 CPS scores derived from paired resected primary tumors (PTs) and lymph node metastases (LMs) in patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC). DESIGN.­: We identified 38 resected p16+ OPSCCs for which paired PTs and LMs were available. PD-L1 immunohistochemistry using the SP263 antibody clone was done on both the PT and the LM. CPS scoring was performed by 4 observers, and data were analyzed at the CPS cut points of greater than or equal to 1 and 20 in regard to interobserver and interspecimen agreement. RESULTS.­: Overall agreement between consensus CPS scoring of PT and LM was seen in 76% of paired specimens (κ = 0.53). No specimen received a negative consensus score. Interobserver agreement for both PT and LM was fair to substantial (κ = 0.54 and 0.51, respectively) and was inferior to that seen in a prospective series of unselected head and neck squamous carcinoma cases evaluated at our institution (κ = 0.84). CONCLUSIONS.­: Given the high rates of interobserver and interspecimen variability, evaluation of additional material or by additional observers may be of value in performing CPS scoring in cases of p16+ OPSCC. This is particularly the case when a negative or low-positive result is being evaluated in a patient who is otherwise a good candidate for immunotherapy.

Cancer-associated thrombosis by cancer sites and inherited factors in a prospective population-based cohort.

Cancer-associated thrombosis (CAT) is common and associated with mortality. We estimated CAT rate by cancer sites and inherited factors among cancer patients from the UK Biobank (N =70,406). The 12-month CAT rate after cancer diagnosis was 2.37% overall but varied considerably among cancer sites. Among the 10 cancer sites classified as 'high-risk' of CAT by the National Comprehensive Cancer Network guidelines, 6 had CAT rate <5%. In contrast, 5 cancer sites classified as 'average-risk' by the guidelines had CAT rate >5%. For inherited risk factors, both known mutation carriers in two genes (F5/F2) and polygenic score for venous thromboembolism (VTE) (PGSVTE) were independently associated with increased CAT risk. While F5/F2 identified 6% patients with high genetic-risk for CAT, adding PGSVTE identified 13 % patients at equivalent/higher genetic-risk to CAT than that of F5/F2 mutations. Findings from this large prospective study, if confirmed, provide critical data to update guidelines for CAT risk assessment.

A randomized phase II study of cetuximab every 2 weeks at either 500 or 750 mg/m2 for patients with recurrent or metastatic head and neck squamous cell cancer.

Cetuximab is typically administered on a weekly schedule for patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC). This study explores cetuximab administered every 2 weeks (q2w). In this multicenter randomized prospective phase II study, eligible patients (≤2 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease; ECOG performance status ≤2) were randomized to receive cetuximab q2w at 500 mg/m(2) (Group A) or 750 mg/m(2) (Group B). The primary end point was response rate (RECIST 1.0). Sixty-one patients were enrolled: 35 in Group A and 26 in Group B, which was closed early for lack of efficacy. Confirmed partial response rates were 11% for Group A (4/35) and 8% for Group B (2/26) according to intention to treat analysis. Partial responses occurred only among patients whose primary tumors were in the oral cavity or larynx. Median progression-free survival (PFS) and median overall survival (OS) were similar for both groups (PFS, 2.2 and 2.0 months; OS, 7.0 and 9.4 months; Groups A and B, respectively). The most common cetuximab-related adverse events (all grades) among treated subjects included rash, fatigue, and hypomagnesemia. Cetuximab, 500 mg/m(2), q2w achieves similar efficacy as conventional dosing for patients with recurrent or metastatic HNSCC. Escalating the dose to 750 mg/m(2) q2w offers no obvious therapeutic advantage.

Pembrolizumab Plus Ipilimumab Following Anti-PD-1/L1 Failure in Melanoma.

PURPOSE: Combination of antiprogrammed cell death protein-1 (PD-1) plus anti-cytotoxic T-cell lymphocyte-4 (anti-CTLA-4) immunotherapy shows greater response rates (RRs) than anti-PD-1 antibody alone in melanoma, but RR after initial anti-PD-1 and programmed death ligand-1 (PD-L1) antibody progression awaits robust investigation. Anti-CTLA-4 antibody alone after anti-PD-1/L1 antibody progression has a historical RR of 13%. We report the results of the first prospective clinical trial evaluating ipilimumab 1 mg/kg plus pembrolizumab following progression on anti-PD-1 immunotherapy. METHODS: Patients with advanced melanoma who had progressed on anti-PD-1/L1 antibody as immediate prior therapy (including non-anti-CTLA-4 antibody combinations) were eligible. Patients received pembrolizumab 200 mg plus ipilimumab 1 mg/kg once every 3 weeks for four doses, followed by pembrolizumab monotherapy. The primary end point was RR by irRECIST. After 35 patients, the trial met the primary end point and was expanded to enroll a total of 70 patients to better estimate the RR. RESULTS: Prior treatments included 60 on anti-PD-1 antibody alone and 10 on anti-PD-1/L1 antibody-based combinations. Thirteen patients had progressed in the adjuvant setting. The median length of prior treatment with anti-PD-1/L1 antibody was 4.8 months. Response assessments included five complete and 15 partial responses, making the irRECIST RR 29% among the entire trial population. The median progression-free survival was 5.0 months, and the median overall survival was 24.7 months. The median duration of response was 16.6 months. There was no difference in median time on prior anti-PD1/L1 or time to PD1 + CTLA4 initiation between responders and nonresponders. Grade 3-4 drug-related adverse events occurred in 27% of patients. Responses occurred in PD-L1-negative, non-T-cell-inflamed, and intermediate tumor phenotypes. CONCLUSION: To our knowledge, this is the first prospective study in melanoma of pembrolizumab plus low-dose ipilimumab after anti-PD-1/L1 immunotherapy failure, demonstrating significant antitumor activity and tolerability.

PD-L1 CPS Scoring Accuracy in Small Biopsies and Aspirate Cell Blocks from Patients with Head and Neck Squamous Cell Carcinoma.

To evaluate the performance characteristics of PD-L1 immunohistochemistry (IHC) combined positive scoring (CPS) in core biopsies and aspirate cell blocks from patients with head and neck squamous cell carcinoma (HNSqCCa). PD-L1 IHC using the SP263 antibody was performed on 20 paired cases which consisted of a small biopsy and an excisional specimen. The scores were compared at both the 1% and 20% cutpoints. Using the CPS result obtained from the resected specimen or excisional biopsy as the gold standard, PD-L1 IHC performed on the core biopsy or cell block identified 4 of 6 positive cases (66%) at the 20% cutpoint and 12 of 17 (70%) positive patients at the 1% cutpoint. False positive cases were uncommon at both cutpoints. CPS scoring should be used with caution in small biopsies from patients with HNSqCCa. A negative result should prompt consideration of an excisional biopsy and repeat testing.

Phase II randomised discontinuation trial of brivanib in patients with advanced solid tumours.

BACKGROUND: Brivanib is a selective inhibitor of vascular endothelial growth factor and fibroblast growth factor (FGF) signalling. We performed a phase II randomised discontinuation trial of brivanib in 7 tumour types (soft-tissue sarcomas [STS], ovarian cancer, breast cancer, pancreatic cancer, non-small-cell lung cancer [NSCLC], gastric/esophageal cancer and transitional cell carcinoma [TCC]). PATIENTS AND METHODS: During a 12-week open-label lead-in period, patients received brivanib 800 mg daily and were evaluated for FGF2 status by immunohistochemistry. Patients with stable disease at week 12 were randomised to brivanib or placebo. A study steering committee evaluated week 12 response to determine if enrolment in a tumour type would continue. The primary objective was progression-free survival (PFS) for brivanib versus placebo in patients with FGF2-positive tumours. RESULTS: A total of 595 patients were treated, and stable disease was observed at the week 12 randomisation point in all tumour types. Closure decisions were made for breast cancer, pancreatic cancer, NSCLC, gastric cancer and TCC. Criteria for expansion were met for STS and ovarian cancer. In 53 randomised patients with STS and FGF2-positive tumours, the median PFS was 2.8 months for brivanib and 1.4 months for placebo (hazard ratio [HR]: 0.58, p = 0.08). For all randomised patients with sarcomas, the median PFS was 2.8 months (95% confidence interval [CI]: 1.4-4.0) for those treated with brivanib compared with 1.4 months (95% CI: 1.3-1.6) for placebo (HR = 0.64, 95% CI: 0.38-1.07; p = 0.09). In the 36 randomised patients with ovarian cancer and FGF2-positive tumours, the median PFS was 4.0 (95% CI: 2.6-4.2) months for brivanib and 2.0 months (95% CI: 1.2-2.7) for placebo (HR: 0.56, 95% CI: 0.26-1.22). For all randomised patients with ovarian cancer, the median PFS in those randomised to brivanib was 4.0 months (95% CI: 2.6-4.2) and was 2.0 months (95% CI: 1.2-2.7) in those randomised to placebo (HR = 0.54, 95% CI: 0.25-1.17; p = 0.11). CONCLUSION: Brivanib demonstrated activity in STS and ovarian cancer with an acceptable safety profile. FGF2 expression, as defined in the protocol, is not a predictive biomarker of the efficacy of brivanib.

Association of a Proactive Swallowing Rehabilitation Program With Feeding Tube Placement in Patients Treated for Pharyngeal Cancer.

Importance: A proactive speech and language pathology (SLP) program is an important component of the multidisciplinary care of patients with head and neck squamous cell carcinoma (HNSCC). Swallowing rehabilitation can reduce the rate of feeding tube placement, thereby significantly improving quality of life. Objective: To evaluate the initiation of a proactive SLP rehabilitation program at a single institution and its association with rates of feeding tube placement and dietary intake in patients with HNSCC. Design, Setting, and Participants: Cohort study at a tertiary care and referral center for patients with HNSCC serving the northern Chicago region. Patients were treated for squamous cell carcinomas of the hypopharynx, oropharynx, and nasopharynx from 2004 to 2015 with radiation or chemoradiation therapy in the definitive or adjuvant setting. Patients who received less than 5000 cGy radiation or underwent reirradiation were excluded. Interventions: A proactive SLP program for patients with HNSCC was initiated in 2011. Study cohorts were divided into 2 groups: 2004 through 2010 and 2011 through 2015. Main Outcomes and Measures: Primary outcome variables were SLP referral placement and timing of the referral. Secondary outcomes were feeding tube placement and ability to tolerate any oral intake. Results: A total of 254 patients met inclusion criteria (135 before and 119 after implementation of SLP program; median age, 60 years [range, 14-94 years]; 77% male). With the initiation of a proactive SLP program, pretreatment evaluations increased from 29 (21.5%) to 70 (58.8%; risk ratio [RR], 2.74; 95% CI, 1.92-3.91), and rate of referral overall at any time increased from 60.0% to 79.8% (RR, 1.33; 95% CI, 1.13-1.57). Feeding tube placement rates decreased from 45.9% (n = 62) to 29.4% (n = 35; RR, 0.64; 95% CI, 0.46-0.89). Among patients receiving a swallow evaluation, feeding tube requirements were less frequent for those receiving a pretreatment evaluation (31 of 99 [31%]) than for those referred during (11 of 18 [61%]) or after (38 of 59 [64%]) treatment. The rate of tolerating any oral intake at the end of treatment improved from 71.1% (n = 96) in the preimplementation period to 82.4% (n = 98; RR, 1.16; 95% CI, 1.01-1.33). Conclusions and Relevance: A proactive SLP program can be successfully established as part of the multidisciplinary care of patients with HNSCC and improve patient quality of life.

Perspectives of Health-Care Providers Toward Advance Care Planning in Patients With Advanced Cancer and Congestive Heart Failure.

BACKGROUND: Advance care planning (ACP) discussions afford patients and physicians a chance to better understand patients' values and wishes regarding end-of-life care; however, these conversations typically take place late in the course of a disease. The goal of this study was to clarify attitudes of oncologists, cardiologists, and primary care physicians (PCPs) toward ACP and to identify persistent barriers to timely ACP discussion following a quality improvement initiative at our health system geared at improvement in ACP implementation. METHODS: A 20-question, cross-sectional online survey was created and distributed to cardiologists, oncologists, PCPs, and cardiology and oncology support staff at the NorthShore University HealthSystem (NorthShore) from February to March 2015. A total of 117 individuals (46% of distributed) completed the surveys. The results were compiled using an online survey analysis tool (SurveyMonkey, Inc., Palo Alto, California, USA). RESULTS: Only 15% of cardiologists felt it was their responsibility to conduct ACP discussions with their patients having congestive heart failure (CHF). In contrast, 68% of oncologists accepted this discussion as their responsibility in patients with terminal cancer ( P < .01). These views were mirrored by PCPs, as 68% of PCPs felt personally responsible for ACP discussion with patients having CHF, while only 34% felt the same about patients with cancer. Reported documentation of these discussions in the electronic health record was inconsistent between specialties. Among all surveyed specialties, lack of time was the major barrier limiting ACP discussion. Perceived patient discomfort and discomfort of the patient's family toward these discussions were also significant reported barriers. CONCLUSION: Attitudes toward ACP implementation vary considerably by medical specialty and medical condition, with oncologists in this study tending to feel more personal responsibility for these discussions with patients having cancer than cardiologists with their patients having heart failure. Robust implementation of ACP across the spectrum of medical diagnoses is likely to require a true collaboration between office-based PCPs and specialists in both the inpatient and the ambulatory settings.

A phase II trial of O6-benzylguanine and carmustine in patients with advanced soft tissue sarcoma.

PURPOSE: Tumor resistance to alkylating agents such as carmustine (BCNU) has been found to be associated with intracellular expression of O6-methylguanine-DNA methyltransferase (MGMT). Administration of O6-benzylguanine (O6-BG), a substrate that inactivates MGMT, may help overcome chemotherapy resistance. We performed a phase II study to explore the activity of O6-BG in combination with BCNU in patients with advanced soft tissue sarcoma. EXPERIMENTAL DESIGN: Informed consent was obtained from patients with metastatic soft tissue sarcoma naïve to systemic chemotherapy (adjuvant chemotherapy allowed). Patients received O6-BG 120 mg/m2 I.V. followed by BCNU 40 mg/m2 I.V. Treatment was repeated every 6 weeks until disease progression or development of unacceptable toxicity. RESULTS: No objective responses were observed in 12 enrolled patients. Four patients exhibited stable disease lasting 11-25+ weeks. The median overall survival was 16.9 months (95% CI, 2.9-NR). The most common grade 3-4 toxicities were neutropenia, thrombocytopenia, and anemia. Depletion of MGMT activity was demonstrated in peripheral blood mononuclear cells. Immunohistochemical estimation of MGMT expression from archival tissue ranged from 20 to 99% positive staining cells. CONCLUSIONS: Observed toxicities were consistent with previous studies of O6-BG plus BCNU. The degree of MGMT expression was variable in this small sample of heterogeneous sarcomas. Further development of this regimen and dose for the treatment of soft tissue sarcoma is not warranted due to the lack of objective responses.

Phase II trial of gefitinib 250 mg daily in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

PURPOSE: An objective response rate of 11% was reported in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with 500 mg daily gefitinib although the recommended dose in lung cancer is 250 mg. This study evaluated the efficacy and toxicity of 250 mg daily gefitinib in patients with recurrent and/or metastatic SCCHN. EXPERIMENTAL DESIGN: Phase II trial with objective response rate as the primary end point. Measurements of quality of life and levels of serum vascular endothelial growth factor and transforming growth factor-alpha were assessed before and during therapy. RESULTS: In 70 patients, 1 (1.4%) partial response was observed. Median progression-free survival and overall survival were 1.8 and 5.5 months, respectively. Quality of life scores improved transiently during the first weeks of therapy before returning to baseline. Median vascular endothelial growth factor and transforming growth factor-alpha levels were above the normal range but were not predictive of outcome. Four patients experienced grade 3 drug-related adverse events. Rash of any grade was observed in 64% of subjects. Correlation between disease control (partial response + stable disease), progression-free survival, and overall survival and grade of cutaneous toxicity was observed (P = 0.001, 0.001, and 0.008 respectively). CONCLUSIONS: Gefitinib monotherapy at 250 mg in recurrent and/or metastatic SCCHN seems to have less activity than was previously observed for 500 mg daily. A dose-response relationship may exist for this agent in SCCHN and grade of cutaneous toxicity attributable to gefitinib is a clinical predictor of better outcome.

Current clinical immunotherapeutic approaches for head and neck cancer.

It was estimated that 59,340 new cases of head and neck cancer would be diagnosed in the US alone in 2015 and that 12,290 deaths would be attributed to the disease. Local and regional recurrences may be treated with chemotherapy and radiation; however, metastatic head and neck cancer is fatal and is treated with chemotherapy for palliation. Recent successful treatment of a variety of solid and hematological malignancies by immunotherapeutic approaches (i.e. harnessing the body's own immune system to combat disease) has added a fourth therapeutic option for the treatment of cancer. This commentary will review the status of immunotherapies in clinical development for the specific treatment of head and neck cancer.

Targeting pathways mediating resistance to anti-EGFR therapy in squamous cell carcinoma of the head and neck.

INTRODUCTION: As epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of squamous cell carcinomas of the head and neck (SCCHN), several therapeutic agents that target EGFR have been evaluated for the treatment of SCCHN. Although patients with SCCHN derive clinical benefit from anti-EGFR agents, most notably the EGFR monoclonal antibody cetuximab, these patients eventually become resistant to EGFR-based therapies; preclinical studies have shown activation of secondary signaling pathways that lead to resistance to EGFR inhibition and, as such, serve as potential therapeutic targets to overcome resistance to EGFR inhibitors. AREAS COVERED: This review summarizes the results of recently completed trials of anti-EGFR agents in SCCHN, highlights the various mechanisms that drive resistance to EGFR inhibitors in SCCHN, and focuses on several novel targeted agents that could potentially help overcome resistance to EGFR-based therapies in SCCHN. Expert commentary: Due to the development of resistance to EGFR-targeted therapies, novel treatment approaches to overcome resistance are a key unmet need for SCCHN.

Clinical Response of a Patient to Anti-PD-1 Immunotherapy and the Immune Landscape of Testicular Germ Cell Tumors.

Anti-Programed Death 1 (PD-1) is standard immunotherapy for multiple cancers, and the expression of one of its ligands, PD-L1, has been described in germ cell tumors (GCT). Neither the clinical activity of anti-PD-1 nor the incidence of an immunoresponsive tumor microenvironment has been described for GCTs. A patient initially diagnosed with melanoma via fine needle aspiration was treated with one dose of antibody to PD-1. A core needle biopsy was subsequently performed to acquire sufficient tissue for molecular analysis, which led to a change in diagnosis to metastatic embryonal carcinoma. The testicular GCT cohort of The Cancer Genome Atlas was analyzed using a T-cell gene signature associated with benefit from immunotherapy. Primary tumors (N = 134) were categorized as high (T-cell-inflamed), medium, or low (non-T-cell-inflamed) by their T-cell signature derived from RNAseq data. Anti-PD-1 induced decreases in serum markers and a 33% reduction in tumor volume. Gene expression revealed a T-cell-inflamed tumor microenvironment in 47% of testicular GCTs, including seminoma (83%) and nonseminoma (17%) tumor subtypes. Expression of alpha-fetoprotein (AFP) RNA correlated with lack of the T-cell signature, with increasing AFP RNA inversely correlating with the inflamed signature and expression of IFNγ-associated genes. These data suggest that GCTs can respond to anti-PD-1 and that gene expression profiling supports investigation of immunotherapy for treatment of GCTs. Cancer Immunol Res; 4(11); 903-9. ©2016 AACR.