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.     

Interpretation of suspect head and neck fixations seen on PET/CT in lung cancer

ObjectivesSmoking is the major risk factor for lung and head and neck cancer. The purpose of the present study was to determine the clinical impact of serendipitously revealed head and neck fixation on PET/CT in patients undergoing investigation for lung cancer.Material and methodsThe reports from PET/CT studies for patients with lung cancer from September 2005 and April 2012 were retrospectively reviewed. Head and neck incidentaloma was interpreted as suggestive of second primary malignancy. These incidental findings were compared with the final diagnosis obtained from clinical and histological investigation.ResultsFive hundred and ninety-two patients were investigated on PET/CT for lung cancer in the study period. PET/CT-positive head and neck lesions suggestive of second primary malignancy were found in 65 (11%) patients. Nasoendoscopy was performed in 23 patients and biopsy in 10. In 4 patients (17.4% of those explored), a second primary malignant lesion was proved on histology: 2 squamous cell carcinomas (larynx and oral cavity), 1 undifferentiated carcinoma (parotid), and 1 osteosarcoma (mandible). At a median 13 months’ follow-up, 3 of the 4 patients with a second primary had died from disease-related causes and 1 was free of recurrence. Metastases from lung adenocarcinoma were found in 2 patients (0.34%).ConclusionsPET/CT detected incidental head and neck malignant tumors in at least 0.68% of lung cancer patients, but in 6.4% of those with suspect head and neck fixation.     

Second primary tumors in patients with carcinoma of the head and neck

With improved loco-regional control of cancer of the head and neck, second primary tumors (SPT) have an increasingly negative impact on survival. The appearance of SPT depends on the location and extension of the primary and is associated with lower survival. SPT were studied in a series of 1493 previously untreated patients with carcinoma of the head and neck and a minimum follow-up of 2 years. SPT occurred in 6.3% (96/1493). SPT were associated with the following primary tumor sites: 10.8% (57/727) larynx, 4% (6/153) hypopharynx, 4% (16/404) oral cavity, and 4% (6/153) oropharynx. Forty-three percent (42.7%) of SPT were carcinomas of the head and neck, 27% bronchogenic carcinomas, and 17.7% esophageal carcinomas. Survival at 6 months, 1 year, 3 years, and 5 years of patients diagnosed as SPT was 62%, 43%, 21%, and 16%, respectively.     

Multiple Primary Malignant Tumors in Patients With Head and Neck Cancer

Multiple primary tumors are a known phenomenon in head and neck cancer. They are partially responsible for the limited improvement in survival of head and neck cancer during the past 20 years. Only a few prospective data have been published about the incidence of metachronous tumors. The authors prospectively studied 127 patients with squamous cell carcinoma of the head and neck. The overall incidence of second primary tumors was 13.5% (simultaneously, 3%; synchronously, 5.5%; and metachronously, 8%). More than 90% of the recurrences of the first primary tumor occurred within the first 2 years following primary treatment, but the second primary tumors continued to occur gradually in the course of follow-up. Most of the second primary tumors were discovered because the patients developed symptoms (14/17). Survival after detection of the second primary tumor was poor. The development of a second primary tumor was of equivalent prognosis to a recurrence of the primary tumor. Future directives include the development of more adequate screening methods. Identification of potential early markers for the development of a squamous cell carcinoma at the level of the mucosa at risk and in serum could be of value for the early detection of individuals at risk.     

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.     

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.     

Trismus in patients with head and neck cancer and 5-year overall survival

Abstract

Background: Trismus is a common complication of radiotherapy for head and neck cancer but its impact on survival is unknown.

Aims/Objectives: This prospective study evaluates the incidence of trismus in patients with head and neck cancer receiving radiotherapy and the impact of trismus on 5-year overall survival.

Material and methods: Two hundred forty-four patients with head and neck cancer were included. All patients received instructions on jaw exercises and were evaluated before initiation of radiotherapy and at 2, 6, and 12 months after termination of radiotherapy.

Results: One year after treatment 25% had a reduced maximum interincisal opening (MIO) of 13?mm or more as compared to the pretreatment MIO. Trismus was most prevalent in patients with oral and oropharyngeal cancer. A trend towards worse 5-year overall survival was seen among patients with trismus.

Conclusions: The trismus rate was approximately 30% at 12 months. Jaw exercises should primarily be offered to patients with oral and oropharyngeal cancer who are most likely to benefit. Further studies are required to investigate the effect of trismus on survival.

Significance: This study identifies patients likely to benefit from jaw exercises and provides basis for further research on trismus and survival.     

Cáncer de hipofaringe: análisis de la evolución y los resultados del tratamiento en nuestro medio

ObjectiveHypopharyngeal carcinoma is an aggressive malignancy usually diagnosed at a late state, thereby resulting in overall poor prognosis and low survival rates for these patients. The purpose of this study is to present the progress and outcomes of patients treated for hypopharyngeal carcinoma at our department.Material and methodWe retrospectively reviewed 89 patients who had been diagnosed with hypopharygeal carcinoma between 1980 and 2005. Most of the tumours were advanced (T3 and T4) and 73 % showed palpable regional metastases at presentation.ResultsThe five-year survival rate was 40.7 %. The overall incidence of distant metastases and subsequent primary neoplasms was 7.5 % and 23.5 %, respectively.ConclusionsHypopharyngeal cancer is still the one with the worst prognosis in the head and neck area. The poor survival rate seems to be related primarily to advanced stage disease at presentation and particularly to the status of cervical lymph-node metastases.     

Pretherapeutic nutritional/inflammatory factors as predictors for survival of both early and advanced staged head and neck cancer patients

ObjectivesMalnutrition and inflammation are common in patients with head and neck cancer and are closely associated with prognosis. Although several parameters for evaluating nutritional/inflammatory status have been assessed in relation to the prognosis of patients with head and neck cancer, previous studies primarily included patients with advanced-stage disease. To date, there is no consensus regarding the most reliable parameter for predicting the prognosis of early and advanced-stage head and neck cancer. This study sought to evaluate nutritional/inflammatory prognostic factors before treatment in patients with early and advanced-stage head and neck cancer.MethodsWe retrospectively reviewed medical records of patients treated between 2008 and 2015 at our institution in order to evaluate the effects of nutritional/inflammatory parameters, including C-reactive protein/albumin ratio, modified Glasgow prognostic score, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and Geriatric Nutritional Risk Index, on overall survival. Effects of potential risk factors on overall survival were analyzed by computing Kaplan-Meier estimates; curves were compared using the log-rank test.ResultsA total of 164 patients were enrolled. C-reactive protein/albumin ratio, modified Glasgow prognostic score, platelet/lymphocyte ratio, and Geriatric Nutritional Risk Index were found to be statistically significantly correlated with overall survival. Only the Geriatric Nutritional Risk Index remained statistically significant in the multivariate analysis. The three-year survival rates according to the four-group Geriatric Nutritional Risk Index scores for normal, low, moderate, and high risk were 95.5%, 84.3%, 53.8%, and 23.4%, respectively.ConclusionThe Geriatric Nutritional Risk Index is therefore a useful prognostic factor for patients with early and advanced-stage head and neck cancer.     

Limited English proficiency and head and neck cancer outcomes

PurposeLimited English proficiency (LEP) is common among hospitalized patients and may impact clinical care and outcomes. This study aimed to examine the relationship between LEP and clinical oncological outcomes for patients with head and neck cancer (HNC).Materials and methodsA single center retrospective review was conducted including adult patients with squamous cell carcinoma of the head and neck who received treatment with curative intent between January 1, 2014 and July 1, 2019. Clinical data collected included patient demographics and clinical variables. Univariate and multivariate analysis was performed to determine whether there was an association between LEP and demographic and clinical factors.ResultsThere were 477 patients included in the study; 426 (81%) were English proficient (EP) while 51 (10.7%) were LEP. The LEP patients were diagnosed with cancer at a later overall stage (p = 0.03) and less frequently treated with surgery alone compared to English speaking patients (p < 0.001). After adjusting for overall stage and primary site, LEP patients were significantly more likely to receive primary surgical management compared to primary non-surgical management [OR = 2.29 95% CI (0.93, 5.58), p = 0.008]. There was also a significant association between LEP and primary site of tumor (p < 0.01). Kaplan-Meyer curves for overall survival and disease specific survival showed no significant differences between the two cohorts (p = 0.8063 and p = 0.4986, respectively).ConclusionsLEP may impact access to care resulting in more advanced overall tumor stage at presentation and treatment with primary surgery compared to non-surgical management after adjusting for tumor stage and primary site. Interventions to provide better access to care, awareness of HNC in the LEP populations, and earlier detection may improve outcomes for LEP patients.     

Multiple primary carcinomas in patients with head and neck malignancies

BACKGROUND: Multiple primary tumors can lead to diagnostic and therapeutical problems. In this study we surveyed frequency, localisation, diagnostic, chronologic and therapeutic aspects of multiple primary carcinomas in patients with head and neck tumors. PATIENTS AND METHODS: The data of 843 patients from the tumor registry of the ENT-clinic Aachen were retrospectively studied. RESULTS: Larynx (41.87%) and oropharynx (12.57%) were the main localisation of the first primary neoplasma. In 65 patients (7.71%) multiple primary tumors were observed. 24.6% of these tumors occurred synchronously. Preferential localisation of a second tumor were lung (20%), oral cavity (15.3%) and larynx (13.8%). 28.57% of the metachronous tumors were observed after more than five years. In 46.15% clinical complaints led to the suspicion of a second tumor. Panendoscopy was the most reliable diagnostic procedure. The survival rate and time was significantly reduced in patients with synchronous tumors. 3-year survival rate was 15% compared to 81% in patients with metachronous tumor appearance (p < 0.0001). CONCLUSION: Patients with head and neck tumors have a high incidence of multiple primary malignomas varying from the region of the first presentation of a malignant tumor. Concepts comprising surgery provide the highest survival rates. Because of the high incidence of metachronous carcinomas after five years found in this study, the authors regard a prolonged follow-up period as necessary.     

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.     

An evaluation of the diagnostic methods in head and neck cancer of unknown primary site

Abstract

Background: Various detection methods to identify the primary in head and neck cancer of unknown primary (HN-CUP) require evaluation to improve and standardize management.

Objectives: To evaluate the use of different diagnostic methods, which aim at decreasing the incidence of HN-CUP.

Material and methods: We conducted a retrospective analysis of patients with HN-CUP at the Helsinki University Hospital during 1995–2011. We evaluated clinical assessment, definitive treatment, histopathology, and follow up. We analyzed the success in identifying the primary site to show any changes in diagnostic methods over time.

Results: Frequency of HN-CUP and success in identifying the primary site have remained constant despite the addition of PET-CT and determination of human papilloma virus (HPV) status in diagnostics. Among 133 patients, the diagnostic work up identified the primary site in 53% and the oropharynx predominated (69%). This left 85 patients with HN-CUP and 5-year overall and disease-free survival rates were 71 and 69%, respectively.

Conclusions: Panendoscopy including tonsillectomy should not be omitted in the work up.

Significance: We demonstrate a steady frequency of HN-CUP and constant success in identifying the primary site. Detection of a primary later in the follow up did not impact the survival.     

Secondary primary malignancies in head and neck squamous cell carcinoma.

Second primary malignancies pose a significant clinical challenge to the head and neck oncologist. The prognosis for these patients is poor and therefore early detection of these tumours is essential. There are considerable differences in the reported cohorts of patients and the biological behaviour of these tumours throughout the world literature. This is particularly marked when there is considerable demographic variation present. The behaviour of second primary malignancies in 425 Irish patients with head and neck cancer was reviewed retrospectively. The overall incidence of second cancers was 8.5 per cent. There were a higher proportion of oral cancer patients 47 per cent, the second cancers overall presented with a more advanced T stage, and the overall five-year survival was much lower than that of the index tumour.     

Panendoscopy as a screening procedure for simultaneous primary tumors in head and neck cancer

Head and neck cancer is often associated with second primary neoplasms. These cancers most commonly involve other regions of the head and neck, esophagus, and lung. The majority of cases are also squamous cell carcinomas. In view of this rather frequent occurrence of multiple primary cancers and how they adversely affect the patient's survival, it becomes imperative to analyze how the clinician can intervene effectively. One such approach is to detect multiple primaries as early as possible. As such, panendoscopy as a part of the tumor-staging procedure has been advocated by many investigators to search for simultaneous second primary malignant neoplasms in patients presenting with head and neck cancer. In a 24-month period, data were gathered from 127 consecutive patients referred to University Hospital, Ghent with previously untreated, squamous cell carcinomas of the head and neck. One hundred-eighteen patients underwent an endoscopic examination under general anesthesia, during which 4 simultaneous second primary tumors were found in 3 patients. This represents an incidence of 3.4% of simultaneous second primary neoplasms. The results for the different parts of the endoscopy are discussed and compared with literature findings. Guidelines are given for the initial evaluation of the head and neck cancer patient.     

Multiple primary malignant tumours in patients with head and neck cancer: the implications for follow-up

The pattern of second primary cancer occurrence in 518 Scottish patients with head and neck cancer was determined by a retrospective study. The overall incidence of second cancers was 9% but the true incidence increased steadily in the years following initial diagnosis to reach a maximum of 21% at 11 years. After 4 years of follow-up patients were more likely to die from a second primary cancer than from the effects of the initial tumour. The Scottish cohort differed from previously reported, overseas, study groups in having a high incidence of second primary cancers in sites outside the upper aerodigestive tract. This potential demographic difference suggests a need for local audit prior to design and implementation of screening protocols for second primary cancers.     

Multiple primary malignant tumours in patients with head and neck cancer: the implications for follow-up.

The pattern of second primary cancer occurrence in 518 Scottish patients with head and neck cancer was determined by a retrospective study. The overall incidence of second cancers was 9% but the true incidence increased steadily in the years following initial diagnosis to reach a maximum of 21% at 11 years. After 4 years of follow-up patients were more likely to die from a second primary cancer than from the effects of the initial tumour. The Scottish cohort differed from previously reported, overseas, study groups in having a high incidence of second primary cancers in sites outside the upper aerodigestive tract. This potential demographic difference suggests a need for local audit prior to design and implementation of screening protocols for second primary cancers.     

The impact of virus in N3 node dissection for head and neck cancer

This study is to determine the impact of virus in surgical outcomes among patients of head and neck cancer with N3 lymph node metastasis. A retrospective analysis was conducted for 32 patients with operable N3 neck metastasis undergoing surgical treatment between January 1987 and October 2006. The nuclei of the tumor cells were investigated for the presence of human papillomavirus (HPV) and Epstein–Barr virus (EBV) DNAs and were taken into account as the variable for survival analysis. The primary sites were oropharynx in 11 patients, tongue in 3, buccal mucosa in 1, hypopharynx in 8 and unknown primary in 9. The five-year cumulative overall survival rate was 40.7% and 5-year cumulative regional control rate was 55.8%. The 5-year cumulative overall survival rate of patients with unknown primary site (72.9%) and HPV or EBV positive in the tumor (77.8%) were significantly higher than those patients with known primary site (31.3%) and HPV or EBV negative in the tumor (27.4%), respectively (P = 0.0335 and P = 0.0348, log rank test). In conclusion, surgery with adjuvant therapy offers reasonable outcomes for operable N3 node in head and neck cancer in our cohort. In addition, patients with HPV or EBV positive in the tumor have a better survival.     

Pretreatment elevated mean corpuscular volume as an indicator for high risk esophageal second primary cancer in patients with head and neck cancer

ObjectiveEsophageal cancer is the most common second primary cancer (SPC) in patients with head and neck cancer (HNC). Esophageal SPC has a negative impact on survival. Elevated mean corpuscular volume (MCV) is an accepted predictor of esophageal cancer risk. The aim of this study was to elucidate the usefulness of elevated MCV as an indicator of a high risk for esophageal SPC.MethodsWe retrospectively reviewed the medical records of patients with oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinoma who underwent chemoradiotherapy between 2003 and 2012. We excluded patients younger than 20 years or who had received treatment for esophageal cancer and who had a histologically unproven lesion. Patients were divided into two groups according to their MCV. The cut-off for MCV was defined by receiver operating characteristics curve analysis. The primary endpoint was the cumulative incidence of esophageal SPC.ResultsA total of 295 patients were included. The median follow-up period for surviving patients was 7.4 years and the optimal cut-off point was 99.0 fL. One hundred ninety-five patients (66%) had an MCV < 99.0 fL and 100 (34%) had an MCV ≥ 99.0 fL. The 5-year cumulative incidence in patients with an MCV < 99.0 fL and ≥ 99.0 fL was 8.7% and 27%, respectively. In the multivariate analysis, an MCV ≥ 99.0 fL (HR=2.2; 95%CI, 1.1-4.2) was an independent risk factor.ConclusionMCV ≥ 99.0 fL was found to be a risk factor for esophageal SPC. We, therefore, recommend that patients with an MCV ≥ 99.0 fL should undergo intensive monitoring.     

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.