Phase II Trial of Induction Chemotherapy for Advanced Sinonasal Squamous Cell Carcinoma.

Purpose: Outcomes after primary surgery for advanced sinonasal squamous cell carcinoma (SCC) are poor. We tested whether induction chemotherapy (IC) can improve disease control or organ preservation.

Patients And Methods: A phase II trial evaluated previously untreated patients with stage II-IV, M0 sinonasal SCC.

Evolutionary Action Score of Analysis in Pathologically High-Risk Human Papillomavirus-Negative Head and Neck Cancer From a Phase 2 Clinical Trial: NRG Oncology Radiation Therapy Oncology Group 0234.

Purpose: An evolutionary action scoring algorithm (EAp53) based on phylogenetic sequence variations stratifies patients with head and neck squamous cell carcinoma (HNSCC) bearing missense mutations as high-risk, associated with poor outcomes, or low-risk, with similar outcomes as wild-type, and has been validated as a reliable prognostic marker. We performed this study to further validate prior findings demonstrating that EAp53 is a prognostic marker for patients with locally advanced HNSCC and explored its predictive value for treatment outcomes to adjuvant bio-chemoradiotherapy.

Methods And Materials: Eighty-one resection samples from patients treated surgically for stage III or IV human papillomavirus-negative HNSCC with high-risk pathologic features, who received either radiation therapy + cetuximab + cisplatin (cisplatin) or radiation therapy + cetuximab + docetaxel (docetaxel) as adjuvant treatment in a phase 2 study were subjected to targeted sequencing and EAp53 scoring to correlate with clinical outcomes.

Induction chemotherapy with or without erlotinib in patients with head and neck squamous cell carcinoma amenable for surgical resection.

Purpose: Neoadjuvant chemotherapy prior to definitive surgery has been utilized widely for locally advanced oral squamous cell carcinoma (OSCC). We evaluated neoadjuvant erlotinib with platinum-docetaxel vs. placebo with platinum-docetaxel in stage III-IVB OSCC patients.

Precision medicine: preliminary results from the Initiative for Molecular Profiling and Advanced Cancer Therapy 2 (IMPACT2) study.

Precision medicine is associated with favorable outcomes in selected patients with cancer. Herein, we report an interim analysis of IMPACT2, an ongoing randomized study evaluating genomic profiling and targeted agents in metastatic cancer. Patients with metastatic cancer underwent tumor genomic profiling (ClinialTrials.

A Phase II Trial of Alisertib (MLN8237) in Salvage Malignant Mesothelioma.

Lessons Learned: Treatment with the Aurora kinase A inhibitor yields often durable disease control, but limited tumor regression, in heavily pretreated patients with unresectable malignant pleural or peritoneal mesothelioma. In a limited sample size, MYC copy-number gain or gene amplification, a candidate predictive biomarker for alisertib, did not correlate with improved response numbers or patient outcomes.

Background: Malignant mesothelioma is an aggressive disease for which few effective therapies are available.

Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy.

Background: Patients with advanced primary and recurrent salivary duct carcinoma (SDC), a rare and lethal malignancy, have limited therapeutic options. Novel small-molecule agents aimed at targeting critical signaling associated with SDC tumorigenesis may lead to new therapeutic options for patients with these tumors. The human epidermal growth factor receptor 2 (HER2)/phosphoinositide 3-kinase (PI3K) axis, an important oncogenic pathway, has been targeted for therapy in several solid tumors.

Combining Immune Checkpoint Blockade and Tumor-Specific Vaccine for Patients With Incurable Human Papillomavirus 16-Related Cancer: A Phase 2 Clinical Trial.

Importance: In recurrent human papilloma virus (HPV)-driven cancer, immune checkpoint blockade with anti-programmed cell death 1 (PD-1) antibodies produces tumor regression in only a minority of patients. Therapeutic HPV vaccines have produced strong immune responses to HPV-16, but vaccination alone has been ineffective for invasive cancer.

Objective: To determine whether the efficacy of nivolumab, an anti-PD-1 immune checkpoint antibody, is amplified through treatment with ISA 101, a synthetic long-peptide HPV-16 vaccine inducing HPV-specific T cells, in patients with incurable HPV-16-positive cancer.

Comparing Intensity-Modulated Proton Therapy With Intensity-Modulated Photon Therapy for Oropharyngeal Cancer: The Journey From Clinical Trial Concept to Activation.

Intensity-modulated proton therapy minimizes the incidental irradiation of normal tissues in patients with head and neck cancer relative to intensity-modulated photon (x-ray) therapy and has been associated with lesser treatment-related toxicity and improved quality of life. A phase II/III randomized trial sponsored by the US National Cancer Institute is currently underway to compare deintensification treatment strategies with intensity-modulated proton therapy vs intensity-modulated photon (x-ray) therapy for patients with advanced-stage oropharyngeal tumors. After significant input from numerous stakeholders, the phase III portion of the randomized trial was redesigned as a noninferiority trial with progression-free survival as the primary endpoint.

Erlotinib in the treatment of recurrent or metastatic cutaneous squamous cell carcinoma: A single-arm phase 2 clinical trial.

Background: Cutaneous squamous cell carcinoma (CSCC) is a very common malignancy in which most patients present with localized disease. Recurrent and metastatic disease is rare, and there is no standard therapy. These tumors frequently overexpress the epidermal growth factor receptor (EGFR).

Poly ADP-ribose polymerase-1 as a potential therapeutic target in Merkel cell carcinoma.

Background: Patients with metastatic Merkel cell carcinoma are treated similarly to small cell lung cancer (SCLC). Poly ADP-ribose polymerase-1 (PARP1) is overexpressed in SCLC and response to PARP inhibitors have been reported in patients with SCLC. Our study explores PARP as a therapeutic target in Merkel cell carcinoma.

Single Arm, Phase II Study of Cisplatin, Docetaxel, and Erlotinib in Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinomas.

Lessons Learned: The combination of cisplatin, docetaxel, and erlotinib as frontline treatment for recurrent and/or metastatic head and neck squamous cell carcinomas led to a response rate of 62%.This result exceeded the prespecified target response rate of 50% and represented an improvement compared with historical controls.This regimen warrants further investigation.

Initiative for Molecular Profiling and Advanced Cancer Therapy (IMPACT): An MD Anderson Precision Medicine Study.

Purpose: Genomic profiling is increasingly used in the management of cancer. We have previously reported preliminary results of our precision medicine program. Here, we present response and survival outcomes for 637 additional patients who were referred for phase I trials and were treated with matched targeted therapy (MTT) when available.

Nasopharyngeal carcinoma presenting as an inconspicuous primary lesion with extensive cavernous sinus involvement and temporal lobe extension: a case report and review of literature.

Detection of nodal metastasis in the neck or adjacent structures is common in nasopharyngeal carcinoma (NPC) when there is frank primary disease. Intracranial extension without obvious nasopharyngeal disease is not common. Here, we discuss a patient with NPC that presented with extensive intracranial disease with subtle findings in the nasopharynx.

Gefitinib for patients with incurable cutaneous squamous cell carcinoma: A single-arm phase II clinical trial.

Background: Preclinical data demonstrate a key role for the epidermal growth factor receptor (EGFR) in the carcinogenesis of cutaneous squamous cell carcinomas (CSCCs). There are, however, limited data on the efficacy of EGFR inhibitors in incurable, recurrent, and/or metastatic CSCC.

Objective: To determine the response rate to gefitinib in patients with CSCC not amenable to curative therapy including surgery or radiation.

Outcomes for olfactory neuroblastoma treated with induction chemotherapy.

Background: Oncologic outcomes for induction chemotherapy and its role in patients with advanced olfactory neuroblastoma (ONB) remain unclear.

Methods: A retrospective review of 15 consecutive patients with extensive local invasion and/or nodal disease treated with induction chemotherapy with curative intent followed by definitive local therapy.

Results: The majority of patients were treated with cisplatin and etoposide.

Delayed lower cranial neuropathy after oropharyngeal intensity-modulated radiotherapy: A cohort analysis and literature review.

Background: The purpose of this study was to examine swallowing-related lower cranial nerve palsy (LCNP) in oropharyngeal cancer (OPC) survivors after intensity-modulated radiotherapy (IMRT).

Methods: Patients treated with definitive IMRT (66-72 Gy) were pooled from institutional trial databases. Prospective analyses on parent trials included videofluoroscopy, clinical LCNP examination, and questionnaires pre-IMRT, 6 months post-IMRT, 12 months post-IMRT, and 24 months post-IMRT.

Reduced acute toxicity and improved efficacy from intensity-modulated proton therapy (IMPT) for the management of head and neck cancer.

Cancers in the head and neck area are usually close to several critical organ structures. Traditional external-beam photon radiation therapy unavoidably exposes these structures to significant doses of radiation, which can lead to serious acute and chronic toxicity. Intensity-modulated proton therapy (IMPT), however, has dosimetric advantages that allow it to deposit high doses within the target while largely sparing surrounding structures.

Long-Term, Prospective Performance of the MD Anderson Dysphagia Inventory in "Low-Intermediate Risk" Oropharyngeal Carcinoma After Intensity Modulated Radiation Therapy.

Purpose: To characterize long-term MD Anderson Dysphagia Inventory (MDADI) results after primary intensity modulated radiation therapy (IMRT) for oropharyngeal carcinoma (OPC) among patients with "low-intermediate risk" OPC who would be eligible for current trials (eg, ECOG 3311, NRG HN002, CRUK PATHOS).

Methods And Materials: A retrospective pooled analysis combined data from 3 single-institution clinical trials for advanced-stage head and neck carcinoma. Inclusion criteria were clinical stage III/IV OPC (T1-2/N1-2b, T3/N0-2b) treated with definitive split-field IMRT and prospectively collected MDADI at baseline and at least 1 posttreatment interval available in trial databases.

Predicting two-year longitudinal MD Anderson Dysphagia Inventory outcomes after intensity modulated radiotherapy for locoregionally advanced oropharyngeal carcinoma.

Objectives/hypothesis: To determine the factors associated with longitudinal patient-reported dysphagia as measured by the MD Anderson Dysphagia Inventory (MDADI) in locoregionally advanced oropharyngeal carcinoma (OPC) survivors treated with split-field intensity modulated radiotherapy (IMRT).

Study Design: Retrospective patient analysis.

Methods: A retrospective analysis combined data from three single-institution clinical trials for stage III/IV head and neck carcinoma.

Reirradiation of Head and Neck Cancers With Intensity Modulated Radiation Therapy: Outcomes and Analyses.

Purpose: To review our 15-year institutional experience using intensity modulated radiation therapy (IMRT) to reirradiate patients with head and neck squamous cell carcinomas (HNSCC) and identify predictors of outcomes and toxicity.

Methods And Materials: We retrospectively reviewed the records of 227 patients who received head and neck reirradiation using IMRT from 1999 to 2014. Patients treated with noncurative intent were excluded.

Intensity-modulated proton beam therapy (IMPT) versus intensity-modulated photon therapy (IMRT) for patients with oropharynx cancer - A case matched analysis.

Background: Owing to its physical properties, intensity-modulated proton therapy (IMPT) used for patients with oropharyngeal carcinoma has the ability to reduce the dose to organs at risk compared to intensity-modulated radiotherapy (IMRT) while maintaining adequate tumor coverage. Our aim was to compare the clinical outcomes of these two treatment modalities.

Methods: We performed a 1:2 matching of IMPT to IMRT patients.

Clinical Outcomes and Patterns of Disease Recurrence After Intensity Modulated Proton Therapy for Oropharyngeal Squamous Carcinoma.

Purpose: A single-institution prospective study was conducted to assess disease control and toxicity of proton therapy for patients with head and neck cancer.

Methods And Materials: Disease control, toxicity, functional outcomes, and patterns of failure for the initial cohort of patients with oropharyngeal squamous carcinoma (OPC) treated with intensity modulated proton therapy (IMPT) were prospectively collected in 2 registry studies at a single institution. Locoregional failures were analyzed by using deformable image registration.

Eye-sparing multidisciplinary approach for the management of lacrimal gland carcinoma.

Background: We analyzed local control and early ocular toxicity after eye-sparing management of lacrimal gland carcinoma.

Methods: For consecutive patients with lacrimal gland carcinoma treated during 2007 to 2014, we reviewed tumor characteristics, treatment details, ocular toxic effects, and recurrence.

Results: Twenty patients, median age 55 years, were treated for lacrimal gland carcinoma during the study period; 11 had globe-sparing surgery.

Radiation therapy (with or without neck surgery) for phenotypic human papillomavirus-associated oropharyngeal cancer.

Background: Favorable outcomes for human papillomavirus-associated oropharyngeal cancer have led to interest in identifying a subgroup of patients with the lowest risk of disease recurrence after therapy. De-intensification of therapy for this group may result in survival outcomes that are similar to those associated with current therapy but with less toxicity. To advance this effort, this study analyzed the outcomes of oropharyngeal cancer patients treated with or without systemic therapy.