Dynasplint for the management of trismus after treatment of upper aerodigestive tract cancer: a retrospective study

In order to evaluate the Dynasplint Trismus System (DTS) for the relief of trismus secondary to the treatment of head and neck cancer, we conducted a retrospective chart review of patients who had undergone DTS therapy during a 1-year period. Our inclusion criteria were cancer of the upper aerodigestive tract; treatment with radiation, chemotherapy, and/or surgery; and a maximal incisal opening (MIO) of less than 30 mm. MIO and the rate of improvement of trismus ("gain") were measured at selected intervals. Twenty-six patients met our study criteria; their pretherapy mean MIO was 19.3 mm. At the time of their most recent measurement, the mean MIO had increased to 25.5 mm-a measured gain of 32%. Although the initial rate of gain was 0.36 mm/day during the first 6 weeks, improvement leveled off over time, and the overall rate of gain was 0.16 mm/day. We conclude that the DTS is effective in increasing the mandibular range of motion at a rate of change that is maximized during initial treatment.     

Trismus after partial maxillectomy and radiotherapy: Free flap reconstruction versus prosthetic obturation

ObjectivePartial maxillectomy and postoperative radiotherapy are both risk factors associated with trismus. This retrospective study aimed to evaluate the incidence and severity of trismus in patients following partial maxillectomy with or without postoperative radiotherapy and to compare free flap reconstruction and prosthetic obturation.MethodsA retrospective review of 40 oral cancer patients who underwent partial maxillectomy with or without postoperative radiotherapy was performed. Maximum interincisal distance recorded at least 6 months after surgery was classified according to a revised subjective-objective management-analytical (SOMA) scale and compared between the free flap reconstruction group (n = 12) and the prosthetic obturation group (n = 28).ResultsTrismus was observed in 16/40 (40%) patients, and severe trismus was observed in 4/40 (10%) patients. Although no significant difference in trismus grade was observed between the free flap reconstruction and prosthetic obturation groups, both severe trismus and radiation-induced osteonecrosis were only seen in the prosthetic obturation group with postoperative radiotherapy.ConclusionFree flap reconstruction was preferable to prosthetic obturation to avoid severe trismus and radiation-induced osteonecrosis in patients who underwent both partial maxillectomy and postoperative radiotherapy.     

Trismus and oral health conditions during diagnosis of malignant oral neoplasms

IntroductionTrismus has been considered a late complication of cancer treatment. It can occur prior to treatment, mainly caused by tumor invasion or muscle spasms induced by the presence of the tumor.ObjectiveIn this study, we evaluated the incidence of trismus and its effect on oral health in patients with malignant neoplasms of the oral cavity before performing the cancer treatment.MethodsThis review was carried out via interviews, visual clinical inspection and objective measurement of maximal mouth opening in 35 consecutive patients. Trismus was defined as a maximal mouth opening <35 mm.ResultsTrismus was observed in 15 patients, with a total incidence of 42%. A high rate of tooth loss was recorded, and trismus association with tooth loss was statistically verified using the Chi-square and Fisher's exact tests, the t-student test and Mann–Whitney non-parametric test. All tests were performed at p < 0.05.ConclusionEdentulous patients are eight times more likely to have trismus compared to patients that are partially and fully dentate. Trismus was demonstrated to be correlated with tooth loss; however other oral health conditions were not shown to be a modifying factor.     

Usefulness of human papillomavirus detection in oral rinse as a biomarker of oropharyngeal cancer

Conclusion: The detection of human papillomavirus (HPV)-DNA in oral rinse with auto-nested GP5+/GP6?+?PCR is useful as a biomarker of oropharyngeal cancer.

Background: This study aimed to determine the usefulness of oral rinse to detect HPV-DNA as a biomarker of HPV-positive oropharyngeal cancer (OPC).

Patients and methods: One hundred and ten patients with various head and neck diseases, including 19 patients with OPC, were enrolled. Oral rinse and tonsillar swab were collected, and auto-nested GP5+/GP6?+?PCR for HPV-DNA was performed. For oropharyngeal cancer, p16 immunostaining was also conducted.

Results: The rate of HPV-DNA detection in both oral rinse and tonsillar swab was significantly higher in OPC compared with non-OPC upper respiratory tract cancer and non-cancer diseases. HPV-DNA was detected in oral rinse in nine out of 12 p16-positive OPC cases, while none of the p16-negative OPC cases demonstrated detectable HPV-DNA. All p16-positive cases were also positive for HPV-DNA in tumor tissue. Based on p16 immunostaining, the sensitivity and specificity of HPV-DNA detection in oral rinse were 75% and 100%, respectively. Among eight of nine evaluable OPC cases positive for HPV-DNA in oral rinse at diagnosis, HPV-DNA was undetectable in oral rinse in seven cases after treatment.     

A descriptive study highlighting the differences in the treatment protocol for oral tongue cancer in Sweden and Finland

Abstract

Background and aims: Stage II cancer of the tongue is mostly managed surgically both locally and regionally. However, indications for postoperative radiotherapy and reconstructive options vary between centers. This paper aims to describe differences in treatment in a geographically homogenous cohort.

Methods: A retrospective comparison was made between two cohorts of clinical T2N0 tongue cancer from Finland and Sweden. The Finnish cohort included 75 patients and the Swedish 54. All patients had curative intent of treatment and no previous head and neck cancer. Data analyzed consisted of pathological stage, size and thickness of tumor, frequency of reconstruction, radiotherapy delivered, and survival.

Results: The Finnish cohort included a higher proportion of patients managed with reconstructive surgery (67%) than the Swedish cohort (0%), p?<?.00001. More patients were treated with postoperative radiotherapy (84%) in the Swedish cohort than in the Finnish (54%), p?<?.0002. The Finnish cohort had a higher level of survival and included more frequent downstaging (cTNM to pTNM).

Conclusions and significance: Our data indicate a major difference in the management of T2N0 oral tongue cancer. The optimal cut-off size and growth pattern of the tumor warranting reconstruction should be further evaluated in a prospective manner considering both survival and quality of life.     

Evaluation of survival of patients with locally advanced head and neck cancer treated in a single center

IntroductionEven with improved treatment outcomes with multimodality approaches, the question of what is the best initial treatment for locally advanced head and neck cancer still remains unanswered.ObjectiveTo review the overall survival of a large cohort of head and neck cancer, patients with locally advanced head and neck cancer treated in a single institution.Material and methodsWe studied a cohort of patients with locally advanced head and neck cancer treated in our institution in the last fifteen years. To gather a large sample of patients with adequate follow-up time, a cross-check between ours and Fundação Oncocentro de São Paulo databases were done. We included patients with head and neck cancer, clinical or pathological staging III or IV, treated with surgery followed by radiotherapy or surgery plus chemoradiation or radiotherapy alone or chemoradiation alone.Results796 patients with locally advanced head and neck cancer were included, 88% male, 44% age >60 years and 76% stage IV. The tumor location was the oral cavity (34%), oropharynx (27%), hypopharynx (17%) and larynx (17%). The treatment groups were chemoradiation alone (39.7%), surgery plus chemoradiation (26.3%), surgery followed by radiotherapy (18.5%) and radiotherapy alone (15.5%). Comparing the clinical variables between the treatment groups significant differences in age and clinical stage were observed. With a median follow up of 7.5 years (1–16 years), for the entire cohort, the overall survival at 5 and 10 years was 34.8% and 28%. The overall survival at 5 and 10 years was 16.7% and 12.2% for radiotherapy alone, 38.8% and 26.3% for surgery followed by radiotherapy, 28% and 16.6% for chemoradiation alone, and 37.3% and 23.2% for surgery plus chemoradiation. The staging IV (p = 0.03) and radiotherapy alone (p = 0.05), had a worst survival in multivariate analysis. Surgical groups vs. chemoradiation alone had no significant difference for overall survival.ConclusionThe present study is the largest cohort of locally advanced head and neck cancer of Brazilian patients to evaluate treatment outcomes. Although there were significant clinical differences between surgical and radiotherapy groups, surgery or chemoradiation alone as the initial treatment resulted in no significant difference in survival.     

Coronoidectomy for the treatment of trismus in head and neck cancer patients

OBJECTIVES: Trismus is a common adverse effect of tumor extension or treatment for those with head and neck malignancy. Physical therapy is the mainstay of treatment, but many patients still fail to maintain adequate mouth opening. Coronoidectomy is a treatment option for those with trismus, and the purpose of this study was to evaluate the effectiveness of coronoidectomy in treating trismus refractory to physical therapy. STUDY DESIGN: Prospective case series. METHODS: Eighteen head and neck cancer patients with interincisal distances less than or equal to 20 mm underwent coronoidectomy after failing physical therapy for at least 3 months. All patients had undergone maximal radiation therapy, half after tumor resection. RESULTS: Postcoronoidectomy, mean interincisal distances improved 22.1 mm and 21.8 mm at 6 and 12 months, respectively, with all patients maintaining an interincisal distance greater than or equal to 35 mm. Tumor location, tumor histology, or the addition of surgical resection had no impact on outcome. CONCLUSION: Coronoidectomy is effective at improving trismus refractory to physical therapy in head and neck cancer patients.     

Clinical outcomes of nedaplatin and S-1 treatment with concurrent radiotherapy in advanced head and neck cancer

Conclusion: Nedaplatin and S-1 treatment with concurrent radiotherapy was effective, with acceptable toxicities. This regimen does not require extensive intravenous hydration and continuous infusion. Nedaplatin and S-1 may contribute to better clinical outcomes and improve quality of life for patients. Objectives: We retrospectively analyzed the clinical efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell cancer. Methods: Forty-six patients with oropharyngeal, hypopharyngeal, and laryngeal cancer were treated with S-1 on days 1 through 14 and nedaplatin on day 1 every 4 weeks for two cycles of radiotherapy. Therapeutic responses and adverse events were assessed. Results: Primary site tumors and neck lymph nodes exhibited complete response rates of 91% and 64.3%, respectively. The 4-year relapse-free survival and overall survival rates were 76.2% and 85.3%, respectively. The main grade 3 and 4 toxicities were mucositis (30%), leukopenia (30%), anorexia (22%), dermatitis (15%), and thrombocytopenia (9%).     

Are second primary head and neck cancers with previous hematological malignancy more aggressive than de novo head and neck cancers?

ObjectivesSecondary solid tumors can occur after the treatment of hematological malignancies and are associated with a poor prognosis. We evaluated the survival outcomes of patients with second primary head and neck cancers according to the site of cancer origin, type of hematological malignancy, and age.Materials and methodsWe enrolled all patients who underwent surgery for second primary head and neck cancer and were previously treated for hematological malignancy between 1997 and 2020. We analyzed the survival outcomes of patients with second primary head and neck cancer, and compared them with 3126 de novo head and neck cancer patients diagnosed during the same period at our hospital.ResultsThe 5-year overall survival (OS) rate was significantly worse for second primary head and neck cancer patients than de novo cancer patients (52.0 % and 77.9 %, respectively; p = 0.04) and those results were similarly observed in second primary oral cavity cancer (33.3 % and 75.7 %, respectively; p < 0.01). Patients with myelodysplastic syndrome and acute myeloid leukemia showed significantly worse 5-year OS rate than those with other types of hematological malignancies (p = 0.036). Multivariate analysis showed that bone marrow transplantation (BMT) was a risk factor for the recurrence of head and neck cancers (odds ratio = 6.635, p = 0.042).ConclusionPatients with second primary head and neck cancer, particularly of the oral cavity, had a worse prognosis than patients with de novo head and neck cancer. BMT predicts recurrence in second primary head and neck cancer patients.     

Surgical treatment for pulmonary metastases of squamous cell carcinoma of the head and neck

Purpose: As locoregional control of head and neck cancer has improved, distant metastases have become increasingly common problems.Patients and Methods: To determine the role of surgical treatment, we reviewed 32 patients with squamous cell carcinoma (SCC) of the head and neck who underwent thoracotomy for pulmonary metastases.Results: The overall 5-year survival rate was 32%. The 5-year survival rate of the patients with SCC of the oral cavity was significantly poorer than that of the patients with other primary site (15.4% v 45.2%; P = .01). In the patients with single nodule, extent of the tumor was a significant prognostic factor (P = .007). Mediastinal lymph node involvement (P = .004) and pleural invasion (P = .04) also correlated with survival.Conclusion: TNM classification of the primary tumor did not have an impact on survival in this study. Further studies of a large series should be performed to determine the indications and modalities of the surgical treatment for pulmonary metastases of the SCC of head and neck.     

Efficacy and safety of nivolumab in 100 patients with recurrent or metastatic head and neck cancer – a retrospective multicentre study

Abstract

Background: No large-scale retrospective studies have examined the efficacy and safety of nivolumab.

Objective: This retrospective study aimed to investigate the efficacy and safety of nivolumab administered to patients in multiple facilities.

Material and methods: The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS) and overall survival (OS). For safety, adverse event occurrence rates by grade, deaths and severe adverse events were investigated. OS and PFS were also examined according to whether immune-related adverse events (irAEs) appeared. Statistical analysis was conducted using log-rank testing, with values of p?<?.05 considered significant.

Results: Nivolumab was administered to 100 patients with a history of receiving platinum-based drugs. ORR was 13.5% and disease control rate was 49.0%. Median PFS was 3.7?months. Median OS was 9.6?months. For all grades, irAEs occurred in 30 patients. The 1-year survival rate in the subgroup without irAEs was 34.0%, compared to 52.6% with irAEs (p?=?.041).

Conclusions and significance: The 1-year survival rate was better in patients who developed irAEs. This is a new finding for head and neck cancer. Appearance of irAEs could also be used as an indicator of expected therapeutic effect in head and neck cancer.     

Detection of sentinel lymph node using contrast-enhanced agent,Sonazoid™, and evaluation of its metastasis with superb microvascular imaging in oral and oropharyngeal cancers: a preliminary clinical study

Background: In sentinel lymph node (SLN) biopsy for head and neck cancers, the radioisotope method has been the gold standard. However, this method has several problems, such as unavoidable radiation exposure and requirements of expensive equipment.

Aims/Objectives: To overcome these problems, we evaluated the contrast-enhanced ultrasonography (CEUS)-guided SLN-detection method, and predicted the SLN metastatic status using novel ultrasound technology, superb microvascular imaging (SMI).

Methods: Ten patients (6 with oral and 4 with oropharyngeal cancers) without neck lymph node metastasis were enrolled in this study. Ultrasound contrast agent, Sonazoid^?, was infiltrated into the mucosa at the primary site to observe the lymphatic ducts and SLNs in the neck field. The detected SLNs were examined for blood flow using SMI to categorize the SLNs metastases-positive or negative.

Results: SLNs were successfully detected in 8 out of 10 cases. In 7 out of the 8 cases, in whom SLNs were successfully detected, the metastatic status of SLNs was correctly diagnosed with SMI.

Conclusions and significance: Although more clinical data are needed based on a larger cohort, establishing the CEUS-guided SLN-detection and criteria for the accurate diagnosis of SLN-metastases using SMI would be valuable as an alternative to radioisotope method, in oral and oropharyngeal cancers.     

Surgical versus non-surgical management of early stage oropharyngeal squamous cell carcinoma

National guidelines state that early-stage oropharyngeal carcinoma can be treated by either primary surgery or radiotherapy. There is a paucity of evidence comparing surgery versus non-surgical therapy within the same population. With the shift in head and neck cancer treatment towards primary chemoradiation, the aim of this observational cohort study was to help define whether surgery still has a role for early-stage oropharyngeal disease, using a national prospective audit of all new head and neck cancers recruited between 1999 and 2001 in Scotland. Patients with T1-2 N0 M0 tumours were identified. Patients were divided into those treated surgically (±adjuvant radiotherapy) or non-surgically. Five-year outcome data were calculated. Forty-two patients were treated surgically (13 received adjuvant radiotherapy) and 32 patients treated non-surgically. Disease-specific 5-year survival was 69 and 60%, respectively (p?=?0.22). Locoregional failure occurred in seven of the surgical group and five of the non-surgical group. The success of chemoradiotherapy and the evidence for its use as adjuvant therapy may dissuade clinicians from considering surgical intervention. This study demonstrates the outcomes of surgical and non-surgical therapy within the same population. Where clear margins can be achieved, and in the absence of negative prognostic neck pathology, surgery remains a good option; allowing radiotherapy to be preserved for locoregional failures or second primary tumours. Although there are limitations to this study, it does demonstrate the benefit of prospective population data collection.     

Prospektive Phase-II-Studie zur neoadjuvanten Radiochemotherapie fortgeschrittener, operabler Mundh?hlenkarzinome

PURPOSE: The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent as well as in combination drug regimens. In the present outpatient phase II trial, we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable stage III/IV squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Fifty-three patients were enrolled in this trial during the period from May 1998 to October 2000 and received five cycles weekly of Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3-4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. RESULTS: Fifty-two patients were evaluable for toxicity and response. Complete response was observed in 31 of 52 patients (CR 60%), and partial remission was seen in 21 of 52 patients (PR 40%). In 30 of 52 patients complete pathologic response (pCR 58%) was documented in the resection specimens. The 1-, 2-, and 3-year overall survival rate was calculated as 84%. CONCLUSION: Our present results demonstrated impressive clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as a preoperative treatment modality in advanced oral and oropharyngeal cancer.     

Association between radiotherapy and obstructive sleep apnea in head and neck cancer patients: A systematic review and meta-analysis

ObjectiveOur aim was to investigate association between OSA and radiotherapy in head and neck cancer patients.MethodsOn 9th of September 2018, we have searched 12 electronic databases to retrieve relevant studies. All eligible studies that assessed association between OSA and radiotherapy in head and neck cancer patients were included in our meta-analysis. Quality assessment of included studies was done using the NIH tools for cohort, cross-sectional and case series studies.ResultsFourteen studies met our study selection criteria, and six studies were eligible for our meta-analysis. There was no significant association between occurrence of OSA and radiotherapy in head and neck cancer patients (Odds ratio 1.54, 95% CI [0.66–3.60]; P  =  0.322).ConclusionThese findings point to no significant association between OSA risk and radiotherapy in head and neck cancer patients. We suggest more studies to be conducted to investigate any confounders that may influence the effect of radiotherapy on development of OSA in head and neck cancer patients.     

Head and neck cancer: causes,prevention and treatment

Although head and neck carcinoma ranks fifth among cancer types, patient survival rates have not changed significantly over the past years.ObjectiveTo determine the risk factors, causes, therapies, and prevention measures for head and neck cancer.MethodRisk factors, causes, therapies, and preventive measures for this disease were searched on databases PUBMED, MEDLINE, and SciELO.ResultsAlcohol and tobacco are still atop risk factors. Other factors may influence the development of head and neck carcinoma. Surgery is the main treatment option, and the addition of radiotherapy following surgery is frequent for patients in the early stages of the disease. Other therapies target specific genetic molecular components connected to tumor development. Disease preventive measures include smoking cessation, limiting alcohol intake, preventing exposure to tobacco smoke and environmental carcinogenic agents, early detection of infection by HPV, maintaining oral health, good eating habits, and managing stress.ConclusionAdditional research is needed for a more thorough understanding of the development of head and neck carcinomas and to shed light on new ways to improve therapeutic approaches and interventions.     

Surgery and postoperative radiotherapy a valid treatment for advanced oropharyngeal carcinoma

Since 1992 we have prospectively included all head and neck cancer patients in our health region in a departmental based register. Our hospital takes care of all head and neck cancer patients in our health region consisting of approximately 1 million people. In 1997, we evaluated the results of the treatment of oropharyngeal cancer in the 1992?C1997 period. On the basis of this evaluation, we changed our treatment policy for tonsillar and base of tongue carcinoma. We first changed the treatment for the lesions with worst prognosis, i.e., those with T3?CT4 carcinomas, from radiotherapy only, to radical surgery and postoperative radiotherapy. We have since that time increasingly also operated the smaller oropharyngeal carcinomas. The 2?years?? overall survival and disease-specific survival for all patients diagnosed in the 1992?C1997 period was 56 and 63%, respectively. The results from a similar group of patients in the 6?years?? period from 2000 to 2005, after the change in treatment, have increased to 83 and 88%. When we looked at the subgroup of patients in the 2000?C2005 period treated with surgery and postoperative radiotherapy, 45 out of 69 patients (65%) presenting with an oropharyngeal cancer were fit for operation. With radical surgery and postoperative radiation therapy, the 2?years overall survival is now 91%. The 2-year disease-specific survival is 96% and the locoregional control is 98%. This is a marked improvement as compared to radiotherapy alone and definitely competitive with modern radiochemotherapy.     

Definitive re-irradiation using intensity-modulated radiation therapy in cancers of the head and neck,focusing on rare tumors

Purpose: To analyze the outcomes following re-irradiation for local recurrence of rare head and neck tumors.

Material and methods: We retrospectively analyzed 11 patients who had received intensity-modulated radiation therapy (IMRT) for recurrent tumors in the head and neck except for laryngopharynx.

Results: Primary tumor sites included the maxillary sinus, nasal cavity, and external ear canal in six, three, and two patients, respectively. The median follow-up times were 13 (range, 3–54) months. The median survival time was 17 months with 1- and 2-year survival rates of 63.64 and 39.77%, respectively. Among 11 patients, five experienced local failure in the follow-up period. The 1- and 2-year local control rates were 58 and 47%, respectively. Patients who had received a radiation dose of ≥3?Gy per fraction showed significantly better local control than those receiving less (p?=?.0419). One patient experienced Grade 3 facial pain as acute toxicity. Late toxicities included radiographic findings of partial central nervous system necrosis in three patients and Grade 3 osteonecrosis and Grade 3 facial nerve disorder in one patient.

Conclusions: Re-irradiation of rare head and neck tumors using IMRT for loco-regional recurrence may be an acceptable treatment option.     

Head and neck squamous cell carcinoma and metachronous second primaries

ObjectivesTo assess the rate of second (or more) primaries after treatment for head and neck squamous cell carcinoma (HNSCC), and survival compared to patients with a single head and neck cancer.Material and methodA single-center retrospective study was performed in a University Hospital Center in 541 patients between 2002 and 2010.ResultsOne hundred and forty-one patients (26.06%) presented 172 metachronous cancers. Overall 5-year survival was 20.3% with and 38.1% without metachronous cancer. Median and mean survival were respectively 21.9 and 51 months in patients with a single cancer, versus 13.9 and 26.5 months in case of metachronous cancer. Specific survival was comparable to overall survival. All-cause and specific survival were significantly poorer in metachronous cancer (P = 0.001; log-rank α = 0.05).ConclusionAt least a quarter of HNSCC patients go on to develop a metachronous second primary. These are of poor prognosis, whatever their location.     

Elevation of C-reactive protein during concurrent chemoradiotherapy is a poor predictive factor for head and neck cancer

ObjectiveThe prognostic role of pretreatment C-reactive protein (CRP) has been reported for head and neck cancer. However, little is known about the relationship between the changes in CRP levels during treatment and prognosis. This study aimed to investigate the correlation between CRP elevation during concurrent chemoradiotherapy (CCRT) and survival outcomes.MethodsThe medical records of patients with oropharyngeal, hypopharyngeal, and laryngeal cancer treated with CCRT at the University of Tsukuba Hospital and National Hospital Organization Mito Medical Center from April 2014 to December 2019 were retrospectively reviewed. Patients were divided into normal (<0.3 mg/dl) and elevated (≥0.3 mg/dl) CRP groups according to the CRP level after the first cycle of cisplatin. The primary endpoint was progression-free survival (PFS).ResultsA total of 74 patients were enrolled, of whom 36 (49%) showed elevated CRP levels after the first cycle of cisplatin. The 3-year PFS was 83.3% and 61.0% in the normal and elevated CRP groups, respectively, showing significant differences between the two groups.ConclusionElevated CRP levels after the first cycle of cisplatin is an objective predictive marker for survival in patient with head and neck squamous cell carcinoma treated with CCRT.