Novel Immunotherapeutic Approaches to Treating HPV-Related Head and Neck Cancer.

Head and neck cancer (HNC) is the seventh most common malignancy, with oropharyngeal squamous cell carcinoma (OPSCC) accounting for a majority of cases in the western world. While HNC accounts for only 5% of all cancers in the United States, the incidence of a subset of OPSCC caused by human papillomavirus (HPV) is increasing rapidly. The treatment for OPSCC is multifaceted, with a recently emerging focus on immunotherapeutic approaches. With the increased incidence of HPV-related OPSCC and the approval of immunotherapy in the management of recurrent and metastatic HNC, there has been rising interest in exploring the role of immunotherapy in the treatment of HPV-related OPSCC specifically. The immune microenvironment in HPV-related disease is distinct from that in HPV-negative OPSCC, which has prompted further research into various immunotherapeutics. This review focuses on HPV-related OPSCC, its immune characteristics, and current challenges and future opportunities for immunotherapeutic applications in this virus-driven cancer.

Head and neck cancer.

Head and neck cancer is the seventh most common type of cancer worldwide and comprise of a diverse group of tumours affecting the upper aerodigestive tract. Although many different histologies exist, the most common is squamous cell carcinoma. Predominant risk factors include tobacco use, alcohol abuse, and oncogenic viruses, including human papillomavirus and Epstein-Barr virus. Head and neck malignancies remain challenging to treat, requiring a multidisciplinary approach, with surgery, radiotherapy, and systemic therapy serving as key components of the treatment of locally advanced disease. Although many treatment principles overlap, treatment is generally site-specific and histology-specific. This Seminar outlines the current understanding of head and neck cancer and focuses on treatment principles, while also discussing future directions to improve the outcomes of patients with these malignancies.

Parenteral Bevacizumab for the Treatment of Severe Respiratory Papillomatosis in an Adult Population.

OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis (RRP) is a rare, potentially life-threatening, disease that impacts the voice, breathing, and quality of life of patients. Frequent surgical interventions may be needed to control symptoms. We examined the safety and efficacy of utilizing parenteral bevacizumab in the management of severe RRP in adults. STUDY DESIGN: This is a retrospective review of clinical management approaches in a group of patients with severe RRP defined as having a high disease burden, frequent need for debridement, and/or tracheobronchial disease. Patients were initially treated with 15 mg/kg of bevacizumab at 3-week intervals. Bevacizumab dosing and frequency was then individually titrated down. RESULTS: Fourteen adults received a median of 8.5 (range 2-17) bevacizumab infusions over approximately 24 months. All had a history of laryngeal RRP with 6/14 having additional tracheobronchial lesions. Patients required a median of 4 (range 2-11) procedures in the year prior to treatment. Only 3/10 (30%) patients who continued therapy required any additional procedures. Bevacizumab administration was generally well tolerated, with four patients discontinuing therapy. Medical reasons included severe epistaxis and hypertension and thrombocytopenia in an individual with systemic lupus erythematosus. Common side effects included hypertension (grade 2), headache (grades 1-2), elevated creatinine (grades 1-2), and epistaxis (grade 3). CONCLUSIONS: Intravenous bevacizumab for the primary treatment of severe RRP in adults appears clinically effective and safe. Expected and typically mild side effects related to bevacizumab were observed. Continued investigation of bevacizumab through a prospective clinical trial is warranted. LEVEL OF EVIDENCE: 4. Laryngoscope, 131:E921-E928, 2021.

Multimodal Therapy for Sinonasal Malignancies: Updates and Review of Current Treatment.

OPINION STATEMENT: Sinonasal malignancies pose a significant challenge in management due to their low incidence, biologic diversity, and significant symptom burden. Even though surgery remains the primary therapeutic modality, a multi-modality approach has been shown to benefit a significant proportion of patients and its success depends largely on stage and histologic type. Non-surgical approaches such as novel radiation approaches as well as intensification with systemic therapy hold promise in altering the organ preservation rate as well as overall survival for patients. Practice changing randomized trials to test these novel modalities are overdue and desperately needed.

A Case of Chronic Myelogenous Leukemia Occurring in a Patient Treated for Essential Thrombocythemia.

BACKGROUND Essential thrombocythemia (ET) is one of the BCR-ABL gene fusion negative chronic myeloproliferative disorders (MPDs), which also include polycythemia vera (PV), and myelofibrosis. Few clinical cases have reported the progression of ET to chronic myelogenous leukemia (CML) with the expression of the BCR-ABL gene. This report describes such a case and includes a review of other reported cases of CML co-occurring with BCR-ABL-negative chronic MPDs. CASE REPORT A 49-year-old woman was diagnosed with ET in 2007. Cytogenetic testing was negative for expression of the JAK2 or BCR-ABL1 genes. Eight years later, in January 2015, she presented with excessive fatigue, poor appetite, unintentional weight loss, a white blood cell (WBC) count of 24,700 per mL, hemoglobin of 9.9 g/dl, and a platelet count of 557,000 per mL, with blasts and basophils in the blood film. Cytogenetic analysis with fluorescent in situ hybridization (FISH) confirmed a 9: 22 chromosomal translocation (Philadelphia chromosome), and quantitative reverse transcription polymerase chain reaction (qRT-PCR) detected the expression of the BCR-ABL gene, confirming a diagnosis of CML. In February 2015, first-line therapy commenced with nilotinib, which was changed to imatinib after three months. During the following nine months, qRT-PCR confirmed a trend to deep molecular remission (MR5). However, she developed early myelofibrosis, and myelosuppressive therapy was resumed. CONCLUSIONS This rare case highlights the importance of cytogenetic testing in cases of CMPD that transform to CML, not only to confirm the diagnosis but to plan treatment, as Philadelphia chromosome-positive and -negative cases differ in their management.

Systemic therapy in non-conventional cancers of the larynx.

Laryngeal cancer (LC) remains a challenging disease to treat. The majority of LCs diagnosed worldwide are squamous cell carcinomas (SCC), and current treatment guidelines are designed to address conventional laryngeal SCC. However, several histologically rare tumor types can originate in the larynx. There is a lack of guidelines regarding the best therapeutic approaches to these tumors and their treatment is often modeled after their recommended management at non-laryngeal sites. Understanding the role for systemic therapy in these rare tumors is important, especially for patients with advanced disease or those who are not surgical candidates. We provide in this manuscript a detailed and comprehensive overview of systemic therapy considerations for the following histologic tumor types of the larynx: verrucous carcinoma (VC), HPV-related SCC, basaloid SCC (BSCC), lymphoepithelial carcinoma (LEC), adenosquamous carcinoma (ASC), typical and atypical carcinoid, small cell neuroendocrine carcinoma (SCNC), large cell neuroendocrine carcinoma (LCNC), NUT midline carcinomas (NUTMC), melanoma, adenoid cystic carcinoma, rhabdomyosarcoma (RMS), malignant fibrous histiocytoma (MFH), lymphoma, mucoepidermoid carcinoma (MEC), acinic cell carcinoma, and spindle cell carcinoma (SpCC).

Toxicities of systemic agents in squamous cell carcinoma of the head and neck (SCCHN); A new perspective in the era of immunotherapy.

Squamous cell carcinoma of the head and neck (SCCHN) is a difficult to treat malignancy and represents the seventh most common cancer worldwide. Systemic therapy has a critical role in the treatment of locally advanced and recurrent/metastatic disease. Cytotoxic chemotherapy has been primarily used along with radiation and surgery, with cisplatin being the standard of care choice of therapy. When contraindications to cisplatin exist, other agents such as carboplatin, taxanes, 5-fluorouracil, and cetuximab are used. Similarly, in the advanced or metastatic setting, platinum agents, taxanes and cetuximab have been predominantly utilized. With the recent approval of novel agents such as pembrolizumab and nivolumab, and their distinct toxicity profiles, an understanding of the potential sequelae of the different systemic agents is essential to the careful selection of agents in the advanced disease setting. Going forward, choosing novel agents will be weighed against traditional chemotherapy, and understanding the toxicities at stake is critical in this process. In addition to providing an overview of the toxicity profile of the different systemic agents, we also provide a perspective into the future of SCCHN treatment.

Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia: A Case Report.

Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia.

The Future Prospects of Immune Therapy in Gastric and Esophageal Adenocarcinoma.

The prognosis of esophageal cancers is poor and novel approaches are urgently needed. Despite improvements in outcomes with transtuzumab and ramucirumab, these improvements added an average of only 2 to 3 months with a median overall survival reported to be around 1 year. Comprehensive genomic sequencing has defined some molecular alterations with potential targets, but the majority of patients still do not benefit from druggable targets. Breakthroughs in immune checkpoint blockade have provided new therapeutic options in many cancers. Programmed death ligand 1 (PDL1) overexpression, a possible biomarker predicting response to immune checkpoint inhibitors, approaches forty percent in esophageal and gastric cancers. Translational and molecular studies have shown that esophageal cancers are possible candidate malignancies for immune checkpoint inhibition. In this review, we plan to highlight the mechanisms, preclinical, and early clinical data that provide insight on the role of immune therapeutics in esophageal cancers.

The Evolving and Future Role of Taxanes in Squamous Cell Carcinomas of the Head and Neck: A Review.

IMPORTANCE: Since their discovery in the 1970s, taxanes have maintained widespread clinical use in solid tumors, including squamous cell carcinoma of the head and neck (SCCHN), but SCCHN remains a difficult malignancy to treat, often requiring a multidisciplinary approach involving surgery, radiotherapy, and chemotherapy. Taxanes have been heavily studied in the treatment of SCCHN, and their use is currently in the setting of induction chemotherapy with the TPF (docetaxel, FU, cisplatin) regimen for locally advanced SCCHN, as well as in the concurrent therapy setting. However, there is still no clear guideline or indication for the use of taxanes in SCCHN. OBSERVATIONS: A literature search was completed in PubMed using the search terms "taxane," "head and neck cancer," "docetaxel," "paclitaxel," and "chemotherapy," for articles published between 1990 to 2015. In this review, we provide an overview of the evidence thus far supporting the use of taxanes in the concurrent, induction, and adjuvant settings, as well as their use in the treatment of recurrent or metastatic SCCHN. For locally advanced disease, docetaxel is part of the first line regimen for induction therapy, although the superiority of sequential therapy compared with concurrent therapy is still in question. In addition, several studies have shown at least equivalent outcomes for regimens including taxanes compared with standard platinum-based regimens. In the adjuvant setting, RTOG (Radiation Therapy Oncology Group) 1216 is looking into the prospect of docetaxel as a first-line agent for systemic therapy following surgery. In metastatic disease, various second-line regimens include taxanes, and their use is being considered in first-line therapies as well. Several phase 3 trials involving taxanes are underway, with the possibility that they will provide results that increase taxane use in SCCHN. In addition to reviewing their current use, we also provide an analytical discussion of the projected future role of taxanes in the management of SCCHN. Ongoing and future studies involving taxanes are also discussed. CONCLUSIONS AND RELEVANCE: While the current role of taxane use in SCCHN remains to be established, ongoing and future studies involving taxanes will hopefully solidify their role in the treatment of SCCHN. The future role of taxanes will also be influenced by the introduction of novel taxanes, as well as immunotherapy in the treatment of SCCHN.

Complete Remission of Acute Myeloid Leukemia following Cisplatin Based Concurrent Therapy with Radiation for Squamous Cell Laryngeal Cancer.

Acute myeloid leukemia (AML) is a myeloid disorder with several established treatment regimens depending on patient and leukemic factors. Cisplatin is known to have strong leukemogenic potential and is rarely used even as salvage therapy in relapsed or refractory AML. We present a patient simultaneously diagnosed with AML and squamous cell carcinoma of the larynx, who was found to be in complete remission from AML following treatment with cisplatin based chemoradiotherapy for his laryngeal cancer.

Vertical line quadrisection: "what" it represents and who gets the upper hand.

BACKGROUND: Normal adults demonstrate a slight upward bias (vertical pseudoneglect) when attempting vertical line bisection. The mechanism for this bias is unknown. Activation of the allocentric (object-centered) ventral visual system during attempted bisection may induce this bias. This object-centered ventral stream may also mediate focal attention. As compared to bisection, when normal participants perform a vertical line quadrisection task that requires more focal attention, they may have a greater upward bias. METHODS: Sixteen participants bisected and quadrisected vertical lines. RESULTS: The mean upward bias (deviation error) for the quadrisection tasks was significantly higher than the mean error for the line bisections. CONCLUSIONS: These results are consistent with the hypothesis that activation of the ventral stream by a task that requires focal allocentric attention can induce an upward vertical bias that is greater than the upward bias observed with allocentric line bisection, a task that requires more global attention.