Communicating suffering in primary stage head and neck cancer

The findings presented in this discussion seek to make a contribution to quality of life (QOL) research, by highlighting the import of factors affecting the communication of primary stage head and neck cancer patient's experiences of suffering after treatments by their clinicians. Qualitative research methodology based on open-ended interviews with 18 survivors of American Joint Committee on Cancer (AJCC) Stage I and Stage II, squamous cell carcinoma of the head and neck (SCCHN) were used. The interviews were transcribed verbatim and thematically analysed. In this preliminary analysis, three important themes emerged: (1) a self diminished by cancer; (2) the fear of addiction to pain medications; and (3) hopelessness and the loss of meaning in life after SCCHN. Our present findings indicate that SCCHN patients understand their experiences of cancer and under-report their experiences of suffering mainly because of fear. These include fears of: being further diminished by SCCHN, fears of addiction, and an inability to cope with the additional losses associated with SCCHN. As a consequence, and perhaps, because of a failure the part of clinicians and patients to adequately address these fears, SCCHN patients may also experience greater psychological morbidity, becoming fatalistic about biomedicine's ability to restore them to health after cancer, or related symptoms, including pain, despite being 'cured.' This study provides a perspective on why this under-reporting occurs, thereby potentially enhancing clinician-patient communication and the QOL of SCCHN patients who present with curable disease.     

Dysfunction of the p53 tumor suppressor pathway in head and neck cancer

It is important to examine the abnormality of the entire p53 tumor suppressor pathway in head and neck cancer. We examined the mRNA expressions of p53 regulatory factors, p33ING1 and p14ARF, and a p53-target gene, p21WAF1 in head and neck cancer. Nine of 14 benign pleomorphic adenomas (PAs) and 7 of 8 malignant salivary gland tumors (MSGTs) expressed p33ING1 mRNA. Thirteen of 14 PAs expressed p14ARF mRNA, however, only 1 of 8 MSGTs expressed p14ARF mRNA. Eight of 14 PAs and 7 of 8 MSGTs expressed p21WAF1 mRNA. In salivary gland tumors, there was clear correlation between the expression of p33ING1 and p21WAF1 (p<0.0001, r2=0.53). However, there was no correlation between the expression of p14ARF and p21WAF1 (p=0.6543, r2=0.009). Twenty-six of 28 oral squamous cell carcinomas (SCCs) expressed p33ING1 mRNA. Nineteen of 28 oral SCCs expressed p14ARF mRNA. All of the oral SCCs expressed p21WAF1 mRNA. In oral SCCs, the expressions of both p33ING1 (p=0.009, r2=0.181) and p14ARF (p=0.0009, r2=0.271) correlated with the expression of p21WAF1. Interestingly, 24 of 26 oral SCCs (92%) showed either abnormality of p53 itself or loss of expression of p53 regulatory factors, p33ING or p14ARF. These results suggest that head and neck cancer often involve the dysfunction of p53 tumor suppressor pathway.     

Immunotherapy of head and neck cancer using tumor antigen-specific monoclonal antibodies

Monoclonal antibodies (mAbs) are now commonly used therapeutic agents in cancer patients. Since US Food and Drug Administration approval of cetuximab for head and neck squamous cell carcinoma, it has been used increasingly in this disease. Several other mAbs also are in development or in clinical trials. Recently, evidence has accumulated that mAbs induce activation of cellular immunity, including natural killer and T cells and that this may contribute to clinical response. mAbs have been shown to mediate antibody-dependent cellular cytotoxicity, complement-dependent lysis, and activation of tumor antigen-specific T cells. Various patient and tumor factors, such as polymorphisms in Fcγ receptors expressed by immune cells, activity of T-regulatory cells, and tumor escape through downregulation of antigen-processing machinery in tumor cells, are likely to modulate the immune activation mediated by therapeutic mAbs. Understanding the interplay of these factors is likely to improve the selection of the most appropriate candidates for mAb-based immunotherapy, prediction of clinical response, and our understanding of mechanisms of tumor escape from therapeutic mAbs.     

Combined therapy for stage III-IV head and neck cancer: preliminary results

As part of a combined modality treatment program using chemotherapy, surgery, and/or radiotherapy, 25 patients with previously untreated stage III or IV head and neck cancer received initial combination chemotherapy. Pathologically confirmed complete remission was noted in nine patients (36%). The overall objective major response rate (with all patients included in analysis) was 68%. The chemotherapy regimen included bleomycin, cisplatin, vinblastine, methotrexate, and 5-fluorouracil. A novel concept of drug scheduling was used, based on chemotherapy-induced improvement in RBC deformability. The underlying concept is that improved RBC deformability results in improved capillary blood flow and thereby, increased drug delivery to tumor cells. Treatment resulted in moderate hematologic and renal toxicity with no treatment-related deaths. This exceptionally high, pathologically confirmed complete response rate will hopefully provide a mechanism by which combined modality therapy can adequately be tested for its ability to prolong survival of patients with advanced head and neck cancer.     

Early cancer in the head and neck

In head and neck tumors, there is no definition of early cancer. If T1N0M0, no lymph node and distant metastasis, will be early cancer, it is difficult to detect the tumor at early phase in head and neck tumor except for tongue and laryngeal cancer. Because it is hard to define it at early stage in the tumor surrounding by bony structure or tumor growing endophytically. Although almost tumor of head and neck were easily diagnosed by inspection and palpation, total imaging examination should be done actively for detection of early stage of cancer.     

Inflammatory myofibroblastic tumor of the head and neck

Inflammatory myofibroblastic tumor (IMT) is a rare benign neoplasm. The aim of this study was to enhance the understanding of head and neck IMT and to improve its diagnosis and management. Clinical features and related treatment of 10 IMT cases were retrospectively analyzed and the literature was reviewed. Tumor sites identified included four in the maxillary space, two in the buccal space, two in the parotid gland, one in the post aurem, and one in the neck. Nine of ten patients received local resection, and one of ten patients received a total maxillectomy. One patient had a local recurrence and died, while the other nine patients had no distant metastases and survived. A computed tomography (CT) exam performed on nine of the ten patients showed that six of these nine cases were heterogeneous in density, while the other three cases were homogeneous. Four cases showed marked heterogeneous enhancement, two cases showed mild heterogeneous enhancement, and three cases showed moderate homogeneous enhancement on contrast-enhanced CT images. The incidence of IMT in the head and neck is low, and local resection is currently the best treatment. A prolonged postoperative follow-up period is necessary for patients with IMT.     

Controversies in management of the neck in head and neck cancer

Opinion statement As definitive external radiation and multimodality organ preservation strategies (eg, combined chemotherapy and radiation therapy [CCRT]) improve, the role of surgery is being re-examined in the management of locally advanced head and neck cancer. Consensus regarding the use of neck dissections for complete responders and incomplete responders has yet to be achieved and the data are surprisingly controversial. A possible benefit from neck dissection after a complete response of the primary tumor after CCRT or definitive external radiation for advanced squamous cell carcinoma of the head and neck may only be anticipated in patients with persisting subclinical neck disease who have no other sites of disease. Some clinicians have even argued that the salvage rate for clinically detectable residual neck disease does not justify neck dissection. Randomized data addressing these questions and a trial addressing the accuracy of new imaging modalities, such as postchemotherapy and postradiation positron emission tomography scanning, across multiple institutions would be appropriate. As a department, we are aggressive in our treatment of isolated residual neck disease after CCRT or definitive external radiation and for patients initially diagnosed with N3 nodal disease. We are investigating the use of adjuvant neck brachytherapy at the time of neck dissection and we are pleased with our early results.     

Microsatellite analyses of recurrence or second primary tumor in head and neck cancer

BACKGROUND: In head and neck squamous cell carcinoma, distinguishing second primary tumours and recurrences may help to orient clinical decisions concerning therapy. PATIENTS AND METHODS: A panel of eight microsatellite markers was used to analyse the loss of heterozygosity and genomic instability in a selected group of 32 patients experiencing a recurrence after having undergone surgery for oral or oropharyngeal carcinoma, in order to establish the clonality and origin of the recurrence. RESULTS: Twenty-three patients showed genetic changes in primary and/or relapsing tumour DNA: clonally-related patterns were detected in six cases, whereas the different patterns between paired tumours indicated the presence of a second primary tumour in 17 cases. None of the markers was informative in nine cases. CONCLUSION: Our observations suggest that only a small proportion of patients have primary and secondary tumours developing from a single contiguous altered field (thus indicating a common clonal origin), whereas the metachronous tumour arises in unrelated fields in the majority of cases.     

Chemoprevention in head and neck cancer

It is not a coincidence that the aerodigestive tract has proven such a fertile ground for the evaluation of chemoprevention. The incidence of second primaries and the concept of field cancerization made the need for prevention acute and showed the limitations of even the most curative of treatments. New and presumably less toxic agents are being evaluated; chemoprevention is being applied to asymptomatic populations at higher risk for lung, colon, breast, and other neoplasias. Biomarkers may be instrumental in rapid development of these new clinical applications, but much is still to be done. Yet unanswered is whether suppression of premalignant lesions will ultimately decrease cancer incidence. Survival in the second primary prevention trial has not thus far shown a significant improvement and toxicities were significant. Many questions remain in the study of chemoprevention; head and neck cancer provides a conducive model in which these answers might be found.     

Radiochemotherapy in head and neck cancer

The present paper is based on a talk given, during the meeting of the EORTC Radiotherapy Group, held in Arona (Italy) on April 19-20, 2002. This review analyses many still open questions on combined chemotherapy and radiotherapy in head and neck cancer, on the basis of the available data.The paper may help to point out future directions for novel clinical researches on combined chemotherapy and radiotherapy in head and neck cancer.     

Cytogenetics in head and neck cancer

Cytogenetics or the study of chromosomes has been an important tool in oncology. It localizes the abnormality on a particular chromosome segment as such but, the molecular analysis on the other hand focuses the exact gene of interest. Hence both are complimentary. Classical cytogenetics in combination with recent molecular techniques has given rise to various molecular cytogenetic analytical techniques such as florescent in-situ hybridization (FISH), spectral karyotyping (SKY) and comparative genomic hybridization (CGH). The role of telomeres and its concerned enzyme telomerase is important in carcinogenesis. This article summarizes the various cytogenetic techniques and presents an overall view of the importance of cytogenetcs in head and neck cancer.     

头颈部肿瘤难治性出血的急诊介入栓塞治疗

目的探讨介入栓塞对头颈部肿瘤难治性出血的急诊治疗价值。方法2017年2月至2019年2月中国医学科学院肿瘤医院介入治疗科采用介入栓塞术治疗21例头颈部肿瘤难治性出血患者,回顾性分析其肿瘤治疗史、出血史、血管造影表现、介入栓塞技术成功率、临床成功率和并发症情况。结果21例患者造影阳性率为100%(21/21),其中表现为异常肿瘤染色11例,造影剂外溢5例,假性动脉瘤2例,血管畸形2例,颈外动脉起始部破裂1例。1例颈动脉破裂患者转入综合性医院治疗,余20例患者共行22次介入栓塞治疗,技术成功率为100%(22/22)。4例患者在30 d内发生再出血,临床成功率为80.0%(16/20)。5例(25.0%)患者出现轻度颌面部疼痛,无严重并发症发生。结论急诊介入栓塞治疗头颈部肿瘤难治性出血安全、有效。     

Early stage head and neck non-Hodgkin's lymphoma. The effect of tumor burden on prognosis

Treatment results were investigated in 113 previously untreated patients with clinical Stage I and II (Ann Arbor) non-Hodgkin's lymphoma of the head and neck. Fifty-six Waldeyer's ring, 34 other extranodal sites, and 23 cervical nodal lesions were included. The overall relapse-free survival at 5 years was 41%. Age and Ann Arbor stage influenced relapse-free survival. The results suggested that the tumor cell burden is a fundamental prognostic factor for patients with Waldeyer's ring disease and for patients with only cervical nodal disease. Abdominal relapse was most frequent, followed by generalized relapse. From 1981, patients were randomized in a clinical trial to receive either chemotherapy (cyclophosphamide, vincristine, and prednisone [CVP], five courses) or whole-abdominal irradiation (25 Gy/20 Fr) as an adjuvant therapy. Patients could not tolerate the whole-abdominal irradiation well. A significant improvement in survival has been obtained by adjuvant chemotherapy.     

Taxanes in head and neck cancer

Paclitaxel and docetaxel are cytotoxic agents that act on the microtubule system and cause cell death. They are active in patients with squamous cell carcinoma of the head and neck region. They can be combined with other cytotoxic agents and radiotherapy with acceptable toxicity. This article reviews of both docetaxel and paclitaxel data in this patient population. Taxanes do not yet have a a license for use in the standard treatment of patients with head and neck cancer in Europe.     

Imaging in head and neck cancer

Opinion statement The goals of imaging in head and neck cancer are to establish tumor extent and size, to assess nodal disease, to evaluate for perineural tumor spread, and to distinguish recurrent tumor from post-treatment changes. MRI is the preferred modality for assessment of nasopharyngeal, sinonasal, and parotid tumors, because of better contrast resolution, high frequency of perineural spread, and less prominent motion artifacts. MRI is the best modality to delineate the extent of intraorbital and intracranial extension of malignant tumors. Tumors of the oropharynx, larynx, and hypopharynx are frequently primarily imaged with CT, which is less affected by breathing and swallowing artifacts. MRI is also the initial study of choice for tumors confined to the oral tongue, and possibly also for other oral cavity locations because MRI is superior in detection of tumor spread into the bone marrow. There is no clear advantage of CT or MRI for evaluation of nodal disease. Positron emission tomography (PET) is very sensitive for metastatic lymph nodes that are at least 8 mm in size and is the technique of choice in dubious cases. Imaging-guided biopsies are performed whenever needed. For imaging of treated head and neck cancer, PET scans have been found to generally offer higher sensitivity than MRI or CT. Combined PET/CT may be the modality of choice because it almost completely eliminates the false-positive and false-negative PET findings. Patients with head and neck cancer who are referred to tertiary care centers commonly arrive with cross-sectional images obtained at other institutions. Reinterpretation of these studies by dedicated radiologists frequently leads to changes in findings, which alter treatment and affect prognosis.     

F-FDG-PET imaging in radiotherapy tumor volume delineation in treatment of head and neck cancer

Purpose

To determine the impact of ¹⁸F-fluorodeoxyglucose positron emission tomography (PET) in radiotherapy target delineation and patient management for head and neck squamous cell carcinoma (HNSCC) compared to computed tomography (CT) alone.

Materials and methods

Twenty-nine patients with HNSCC were included. CT and PET/CT obtained for treatment planning purposes were reviewed respectively by a neuroradiologist and a nuclear medicine specialist who were blinded to the findings from each other. The attending radiation oncologist together with the neuroradiologist initially defined all gross tumor volume of the primary (GTVp) and the suspicious lymph nodes (GTVn) on CT. Subsequently, the same radiation oncologist and the nuclear medicine specialist defined the GTVp and GTVn on ¹⁸F-FDG-PET/CT. Upon disagreement between CT and ¹⁸F-FDG-PET on the status of a particular lymph node, an ultrasound-guided fine needle aspiration was performed. Volumes based on CT and ¹⁸F-FDG-PET were compared with a paired Student’s t-test.

Results

For the primary disease, four patients had previous diagnostic tonsillectomy and therefore, FDG uptake occurred in 25 patients. For these patients, GTVp contoured on ¹⁸F-FDG-PET (GTVp-PET) were smaller than the GTVp contoured on CT (GTVp-CT) in 80% of the cases, leading to a statistically significant volume difference (p = 0.001). Of the 60 lymph nodes suspicious on PET, 55 were also detected on CT. No volume change was observed (p = 0.08). Ten biopsies were performed for lymph nodes that were discordant between modalities and all were of benign histology. Distant metastases were found in two patients and one had a newly diagnosed lung adenocarcinoma.

Conclusions

GTVp-CT was significantly larger when compared to GTVp-PET. No such change was observed for the lymph nodes. ¹⁸F-FDG-PET modified treatment management in three patients, including two for which no curative radiotherapy was attempted. Larger multicenter studies are needed to ascertain whether combined ¹⁸F-FDG-PET/CT in target delineation can influence the main clinical outcomes.     

Personalized cancer vaccination in head and neck cancer

Cancer is characterized by an accumulation of somatic mutations that represent a source of neoantigens for targeting by antigen-specific T cells. Head and neck squamous cell carcinoma (HNSCC) has a relatively high mutation burden across all cancer types, and cellular immunity to neoantigens likely plays a key role in HNSCC clinical outcomes. Immune checkpoint inhibitors (CPIs) have brought new treatment options and hopes to patients with recurrent and/or metastatic HNSCC. However, many patients do not benefit from CPI therapies, highlighting the need for novel immunotherapy or combinatorial strategies. One such approach is personalized cancer vaccination targeting tumor-associated antigens and tumor-specific antigens, either as single agents or in combination with other therapies. Recent advances in next-generation genomic sequencing technologies and computational algorithms have enabled efficient identification of somatic mutation-derived neoantigens and are anticipated to facilitate the development of cancer vaccine strategies. Here, we review cancer vaccine approaches against HNSCC, including fundamental mechanisms of a cancer vaccine, considerations for selecting appropriate antigens, and combination therapies.