Oral tongue carcinoma: prognostic changes according to the updated 2020 version of the AJCC/UICC TNM staging system.

Background: This study aimed to evaluate the performance of the 2017 8th TNM edition and the latest update in 2020 compared to the 7th in a large cohort of patients affected by oral tongue squamous cell carcinoma (OTSCC), considering all stages. Materials and methods: The cohort involved 300 patients affected by OTSCC treated with surgery. All cases were classified according to the 7th, 8th (2017), and the latest updated TNM edition (October 2020),. Patients were grouped based on the shift in tumour (T) category, lymph nodal (N) category and final pathological stage. Overall survival (OS) and disease-free survival (DFS) were calculated with the Kaplan-Meier method. Univariate and multivariate analyses were carried out. Results: According to the 7th edition, multivariate analysis OS revealed that stage IV patients had an almost 4-fold risk of death compared to stage I (HR = 3.81 95% CI: 2.32-6.25; p < 0.001). Regarding DFS, stage IV patients had a 2-fold greater risk of relapses, or second primary, than patients in stage I (HR = 2.51 95% CI: 1.68-3.74; p < 0.001). According to 2017 8th edition for OS, stage IV patients presented a 5-fold higher risk of death compared to patients in stage I (HR = 5.18 95% CI: 2.96-9.08; p < 0.001) and almost 4-old greater risk of relapses or second primary compared to patients in stage I considering DFS (HR = 3.61 95% CI: 2.28-5.71; p < 0.001). Regarding the recent edition of 8th TNM (2020), stage IV patients had an almost 5-fold greater risk of death compared to patients in stage I considering OS (HR = 4.84 95% CI: 2.74-8.55; p < 0.001), while for DFS they had 3-fold greater risk of relapse or second primary compared to patients in stage I (HR = 3.13 95% CI: 1.99-4.91; p < 0.001). Conclusions: This study confirmed that the recent update of the 8th edition of the TNM (2020) improves stratification and identification of advanced tumours, reducing the number of T3 compared to the 2017 edition and increasing the number of patients with pT4. This improvement made by the updated edition may reduce the risk of skipping adjuvant therapy.

Tongue cancer treatment and oncological outcomes: The role of glossectomy classification.

BACKGROUND: Nowadays surgery remains the gold standard of treatment for tongue cancer. Via a more clear and precise terminology, the glossectomy classification by Ansarin et al. facilitates shared communication between surgeons, allowing comparison between published research and improving surgical practice and patient care. To establish the association of glossectomies, according to their classification by Ansarin et al. with overall survival (OS), disease-free survival (DSF), and cause-specific survival (CSS) in tongue cancer, we conducted a systemic retrospective study on 300 consecutive patients affected by primary oral tongue cancer and treated with surgery at the European Institute of Oncology, IRCCS (IEO). METHODS: Three hundred patients with tongue squamous cell carcinoma and treated at the Division of Otorhinolaryngology and Head and Neck Surgery of the European Institute of Oncology, IRCCS were cataloged according to the glossectomy classification. OS, DFS, and CSS were compared by surgical treatments. RESULTS: OS-5yrs was 80% for the type I glossectomy group, 75% for type II, 65% for type III, and 35% for type IV-V. DFS-5yrs was 74%, 60%, 55%, and 27%, respectively for I, II, III, and IV-V glossectomy group; CSS-5yrs was 82%, 80%, 72%, and 48%, respectively for I, II, III, and IV-V glossectomy group (p < 0.01). CONCLUSIONS: This study confirmed that the application of the glossectomy classification was statistically correlated with patients' oncological outcomes.

Indication to post-operative radiotherapy for oral cavity squamous cell carcinoma: what's new in the depth of infiltration (DOI) era?

OBJECTIVE: The last edition of the American Joint Committee on Cancer (AJCC eighth) has introduced the depth of infiltration (DOI) as a new prognostic parameter in oral cavity squamous cell carcinomas (OCSCCs). The aim of this study is to analyze the impact of stage migration on the indication to post-operative radiotherapy (PORT). METHODS: OCSCCs treated at two institutions between 2014 and 2019 were retrieved. As per the AJCC eighth, only pT3 primarily OCSCCs were considered; availability of the pathologic specimen was a further inclusion criterion. Risk factors considered for PORT were: pT3-pT4, nodal involvement, positive/close surgical margins, perineural and lymph vascular invasion. RESULTS: 149 patients staged as pT3 AJCC eighth were included. A four-fold increase in the number of patients staged as pT3 from the seventh to the eighth AJCC was found. Stage migration to pT3 was equally due to the downstaging from former pT4 (38%) and upstaging of former pT1-pT2 (35%). Considering the former pT1-pT2 53 patients, 13 (25%) had no risk factors for PORT other than DOI. Among 25 cases with former pT1-pT2 and negative lymph nodes, no additional risk factors were found in 11 (44%). CONCLUSION: 90% of patients had at least one risk factor besides DOI and would have received PORT also according to the AJCC seventh; notably, of former pT1-pT2N0, half of them have been upstaged to pT3 in the current TNM classification. The role of PORT in this cohort of patients has not been clarified yet. ADVANCES IN KNOWLEDGE: Other-than-DOI risk factors leading to PORT indication are highly prevalent in OCSSC patients classified as pT3 per the latest AJCC TNM staging system and should therefore be considered for a comprehensive oncological assessment.

Outcomes of head and neck cancer management from two cancer centres in Southern and Northern Europe during the first wave of COVID-19.

OBJECTIVE: To describe the approach and outcomes from two cancer centres in Southern and Northern Europe during the first wave of coronavirus disease 2019 (COVID-19) of patients with head and neck cancer (HNC). METHODS: Data collection was performed on a retrospective cohort of patients surgically treated for primary HNC between March and May 2020, using data from two tertiary hospitals: the European Institute of Oncology (Milan) and Guy's & St Thomas' NHS Foundation Trust (London). RESULTS: We included 77 patients with HNC. More patients with COVID-19 were taking angiotensin-converting enzyme (ACE) inhibitors and had Clavien-Dindo Classification grade I compared to negative patients, respectively (60% vs 22% [p = 0.058] and 40% vs 8% [p = 0.025]). Multivariate logistic regression analyses confirmed our data (p = 0.05 and 0.03, respectively). Sex and age were statistically significantly different (p = 0.05 and <0.001 respectively), showing more male patients (75% vs 53.66%, respectively) and more elderly patients in Italy than in the United Kingdom (patients aged >63 years: 69.44% vs 29.27%). CONCLUSIONS: This study presents a large cohort of patients with HNC with nasopharyngeal swab during the first peak of the COVID-19 pandemic in Europe. Patients with HNC with COVID-19 appeared more likely to develop postsurgical complications and to be taking ACE inhibitors. The preventive measures adopted guaranteed the continuation of therapeutic surgical intervention.

An innovative tool for mandibular reconstruction in oral malignancies: A pictorial essay.

Mandibular reconstruction is challenging for most head and neck surgeons. Technological advances have led to the development of a new innovative procedure based on the concepts of computer-assisted design (CAD) and virtual surgical planning (VSP). The main disadvantage of this technique is the lack of flexibility, especially in oncology. A possible solution is the development of a semi-standardized mandible and fibula resection cutting guide: the L1® mandible ReconGuide. We provided a step-by-step description of the operative technique for mandibular reconstruction with the L1® mandible ReconGuide. The L1® mandible ReconGuide is a guiding force toward mandibular reconstruction. Moreover, the tool has been designed to suit the needs of the patients, particularly those with oral cancer, thereby permitting intraoperative planning and increasing time and cost effectiveness. In this pictorial essay, we have presented the operative techniques of using the L1® mandible ReconGuide for reconstruction.

The Impact of Post-Operative Radiotherapy in Early Stage (pT1-pT2N0M0) Oral Tongue Squamous Cell Carcinoma in Era of DOI.

Background: This study investigated the role of depth of infiltration (DOI) as an independent prognosticator in early stage (T1-T2N0M0) oral cavity tumors and to evaluate the need of postoperative radiotherapy in the case of patients upstaged to pT3 for DOI > 10 mm in the absence of other risk factors. Methods: We performed a retrospective analysis on patients treated with surgery and re-staged according to the 8th edition of malignant tumors classification (TNM). The role of DOI as well as other clinical/pathological features was investigated at both univariable and multivariable analyses on overall survival (OS), disease free survival (DFS), relapse free survival (RFS), and local RFS. Results: Among the 94 included patients, 23 would have been upstaged to pT3 based on DOI. Multivariable analysis showed that DOI was not an independent prognostic factor for any of the considered outcomes. The presence of perineural invasion was associated with a significant worse RFS (p = 0.02) and LRFS (p = 0.04). PORT was found to be significantly associated with DFS (p = 0.04) and RFS (p = 0.06). Conclusions: The increasing DOI alone was not sufficient to impact the prognosis, and therefore, should not be sufficient to dictate PORT indications in early-stage patients upstaged on the sole basis of DOI.

Autologous freeze-treated bone for mandibular reconstruction after malignant tumor resection: a study of 72 patients.

OBJECTIVE: The aim of the study was to assess the possibility of mandibular reconstruction with autologous freeze-treated bone after mandibular resection for malignant tumors. PATIENTS: The medical records of 72 consecutive patients surgically treated with segmental mandibular resection and reconstruction with autologous freeze-treated mandible were reviewed. RESULTS: All tumors were in stage T4a for deep infiltration of the mandible. Soft tissues were reconstructed with a direct mucosal closure (4 cases), with a pedicled pectoralis flap (17 cases), and with a forearm fasciocutaneous free flap without or with radial periosteum (18 and 33 cases). Four patients presented with a recurrence after previous surgery and radiotherapy, and 26 patients underwent postoperative radiotherapy. We resected the mental arch in 35 cases and the lateral mandible in 37 cases. Forty-one patients (56.9%) retained their autologous mandibular graft. In 31 cases, the bone graft was removed for mucosal dehiscence and bone infection. Lateral resections achieved a better success rate than anterior resections (75.7% vs 37.1%). The pedicled pectoralis flap achieved the worse success rate (35.3%) in comparison with forearm fasciocutaneous flap (66.7%). Postoperative radiotherapy decreased the success rate (40.0% vs 69.1%). CONCLUSIONS: Mandibular reconstruction with autologous frozen bone is an interesting alternative to more sophisticated methods for patients with oral cancer involving the bone. It is time and cost sparing in comparison to fibula or iliac crest flaps. However, in spite of any intraoral reconstruction, the success rate is not stirring. In our opinion, this type of mandibular reconstruction must be reserved to patients with lateral tumors, with poor prognosis, or severe comorbidities not allowing more complex bone reconstruction.

Lymph node metastases in malignant tumors of the paranasal sinuses: prognostic value and treatment.

OBJECTIVE: To assess the frequency of nodal involvement and its prognostic value in malignant tumors of the paranasal sinuses, particularly in maxillary sinus squamous cell carcinoma. DESIGN: Retrospective review. SETTING: Tertiary cancer center. PATIENTS: The medical records of 704 consecutive patients surgically treated for malignant tumors of the paranasal sinuses from January 1968 to March 2003 were reviewed. The tumors were staged according to American Joint Committee on Cancer-International Union Against Cancer 2002 classification. Only patients with clinically positive nodes underwent a neck dissection. MAIN OUTCOME MEASURES: Lymph node metastases (at presentation or during follow-up, occurring alone, or with concurrent local recurrence and/or distant metastasis). Also analyzed were local recurrence (occurring alone or with concurrent distant metastasis), distant metastasis (occurring alone), and overall survival. RESULTS: The tumor site was the ethmoid sinus in 305 cases and maxillary sinus in 399 cases. At baseline, 5 patients (1.6%) in the ethmoid sinus group and 33 (8.3%) in the maxillary sinus group presented with positive nodes (P < .001); during follow-up, nodal recurrences (alone or simultaneous with T and/or M recurrence) occurred in 15 and 51 patients, respectively, and the corresponding 5-year incidence estimates were 4.3% and 12.5% (P = .001). The highest incidence of node metastases was found in maxillary sinus squamous cell carcinoma, particularly in T2 tumors. Five-year overall survival estimates were 45.3% for patients with N0 tumors and 0% for those with N+ (N1, N2, or N3) ethmoid sinus tumors, and 50.6% and 16.8%, respectively, for patients with maxillary sinus tumors. CONCLUSIONS: Lymph node metastases are a poor prognostic factor for patients with malignant tumors of the paranasal sinuses. The incidence of these metastases is low, particularly in ethmoid sinus tumors. A prophylactic treatment of the neck in patients with N0 tumors (surgery or radiotherapy) might be considered in T2 squamous cell carcinoma of the maxillary sinus and in undifferentiated carcinoma of the ethmoid sinus.

Removal of a Frontal Sinus Osteoma and Reconstruction by a Custom-Made Implant with Neuronavigation Assistance.

The authors report the surgical treatment of an extensive right frontal sinus osteoma assisted by neuronavigation and reconstruction by a hydroxyapatite custom-made implant. The patient presents with ptosis, hypoglobus, and proptosis of the right eye, without any visual impairment. Computed tomographic (CT) scan showed a very large bony mass involving right frontal sinus and displacing the orbital roof. A stereolithographic model-guided planning was carried out to obtain a practical simulation of the surgical operation and it was submitted to a new CT scan to acquire the reference point to realize the neuronavigation assistance, and to achieve the template to realize the hydroxyapatite custom-made implant. Intraoperatively, with the help of neuronavigation assistance, osteotomies were performed by piezoelectric device. The reconstruction was made using a hydroxyapatite custom-made implant. The procedure was damage free, the bony mass was excised, and the orbital roof was repaired without any adverse effects. Postsurgical CT scan and scintigraphy showed a good reconstruction and a good-quality osteoblasts activity on the borders of the implant. Osteoma is a benign slow-growing bone tumor, usually involving the frontal sinus. Navigational assistance offers a very important help to perform safe osteotomies. Hydroxyapatite custom-made implant seems to be an excellent reconstructive method.

Lip-splitting in transmandibular resections: is it really necessary?

Mandibular resection approach (Commando or Composite resection) is one of the fundamental techniques for oral and oropharyngeal large tumour resection. We reviewed the charts of patients who underwent a transmandibular resection for an oral and/or oropharyngeal cancer between 1980 and 2002. Of 700 patients who underwent a mandibular resection for cancer, 332 had been operated without lower lip splitting. A mono or bilateral en-block neck dissection was always performed, except in cases of relapses after a prior surgical treatment with neck dissection. We repaired 307 patients with flaps (pedicled or free flaps, with or without bone). Unsplitting of the lip never complicated resection and reconstruction. Furthermore the procedure was time sparing, as we avoided haemostasis and suture of the lip. The cosmetic results were better than those obtained by traditional technique. We used a non-lip-splitting technique also for pull-through, marginal mandibulectomy and, sometimes, for mandibular-swing approaches. In the latter case, the technique has some advantages and disadvantages and must be applied according to circumstances. We can conclude that lip-splitting in transmandibular resection for oral and oropharyngeal tumours is not necessary.

Absence of otoacoustic emissions in insulin-dependent diabetic patients: is there evidence for diabetic cochleopathy?

In order to evaluate cochlear function in Type 1 diabetes mellitus, this study analyses otoacoustic emissions (OAEs) on normal hearing subjects with diabetes and on controls. Patients with Type 1 diabetes (n=60), with a mean age of 31+/-6.23 years, mean disease duration of 17.5+/-8.9 years, and mean HbA1c of 8.1+/-1.8%, of whom 43% had signs of retinopathy and 28% had clinical signs of neuropathy, were studied. All patients underwent an OAE analysis and brainstem-evoked potentials. Fifty-eight normal volunteers were used as controls for the OAE analysis. Seventeen patients (28.3%) had no OAEs in at least one ear and 10% in both ears. The mean intensity of the response was lower in diabetic subjects [7.1+/-4.4 vs. 10.9+/-9.3 dB SPL (sound pressure level)] than in controls. The cochlear impairment was over 5 dB for the 1-kHz frequency, which is the critical level for speech understanding. These findings suggest that cochleopathy can be detected in a relatively high proportion of subjects with Type 1 diabetes in spite of a normal audiometric hearing threshold.

Prophylactic thyroidectomy in MEN 2A syndrome.

Genetic testing is the appropriate procedure in MEN 2A syndrome for the early diagnosis of medullary carcinoma even at a preclinical stage. Prophylactic total thyroidectomy represents the standard preventive and therapeutic surgical approach in the treatment of medullary thyroid carcinoma in MEN 2A syndrome. Our experience has confirmed the presence of CCH and medullary thyroid carcinoma even in clinically negative patients, in agreement with reports in the literature.

Anterior craniofacial resection for malignant paranasal tumors: a monoinstitutional experience of 366 cases.

BACKGROUND: The purpose of this study was to evaluate the results of a mono-institutional series of patients treated with anterior craniofacial resection for malignant paranasal sinus tumors. METHODS: We analyzed all patients with malignant paranasal sinus tumors treated with anterior craniofacial resection at our institution between 1987 and 2007. All tumors were classified according to both the American Joint Committee on Cancer (AJCC)-2002 and the Istituto Nazionale Tumori (INT) classifications. RESULTS: The sample included 366 patients. There was intraorbital spread in 108 cases. The skull base was eroded in 127 patients, with dura or brain involvement in 93 patients. The 10-year disease-specific survival was 53.1%. Histologic subtype, INT stage, surgical margins, and postsurgical radiotherapy were significant, independent predictors for both local relapse and disease-specific survival (DSS). The AJCC-2002 classification was not significant when tested in place of INT stage. CONCLUSION: Our data indicated that craniofacial resection and postsurgical radiotherapy remain the primary option for malignant tumors involving the anterior skull base.

Intestinal type adenocarcinoma of the ethmoid sinus in wood and leather workers: a retrospective study of 153 cases.

BACKGROUND: The purpose of our study was to identify the role of work exposure to organic dusts in patients with malignant paranasal sinus tumors. METHODS: We analyzed all patients surgically treated for a malignant paranasal sinus tumor at our institution between 1987 and 2006. All patients were specifically asked about their occupational history. The tumor site was classified as maxillary or ethmoid sinus. Adenocarcinomas were divided into intestinal type (ITAC) and non-ITAC. RESULTS: The sample included 345 patients with ethmoid sinus and 301 maxillary sinus. Regarding the ethmoid sinus, we found an exposure to organic dusts in 148 of 153 patients with ITAC, in 3 of 16 patients with non-ITAC adenocarcinoma, and in 10 of 176 patients with other tumors. Regarding the maxillary sinus, we found an exposure in 1 of 20 patients with non-ITAC adenocarcinoma and in 4 of 281 patients with other histologies. CONCLUSION: Our study demonstrates that only ethmoid ITACs have an indisputable relationship with the exposure to organic dusts.

Recent advances in managing human papillomavirus-positive oropharyngeal tumors.

Human papillomavirus (HPV) is detected in a subset of patients with head and neck squamous cell carcinoma, most frequently in tumors in the Waldeyer's ring (palatine tonsil and base of tongue). Several studies suggest that patients with HPV-positive tumors have better survival with either concurrent chemoradiation therapy or surgery followed by radiation compared with HPV-negative patients. However, some possible confounding clinicopathologic variables may challenge the validity of this statement, for example, some authors used the TNM (tumor, node, metastasis) grouping stage while others used the primary tumor (T stage), and other studies have demonstrated that tumors with advanced T stage were less likely to be infected with HPV. A large clinical trial with stratification of patients according to all known tumor prognostic factors is crucial to solve the question.

Surgery for malignant maxillary tumors involving the middle cranial fossa.

The purpose of this study was to evaluate the disease-free survival (DFS) of patients with maxillary malignant tumors invading the middle cranial fossa (MCF) who underwent a lateral or anterolateral skull base resection. This study was a retrospective analysis in a tertiary referral center and included 62 patients with maxillary malignant tumors invading the MCF (stage T4b) treated with surgery with or without postoperative radiotherapy. All patients had sharp pain and involvement of at least one branch of the trigeminal nerve. Twenty-eight patients had not been treated previously, and 34 had previously been treated elsewhere. The MCF dura was infiltrated and resected in 36 cases, and in nine of these, there was an intradural extension of the tumor, with temporal lobe and/or cavernous sinus invasion. Thirty-six patients underwent reconstruction with a temporalis muscle pedicled flap, and 26 patients with a free flap. There was a 22% overall rate of postoperative complications, but no intraoperative deaths. The median follow-up time was 49 months (range 2 to 186). Overall DFS was 33.9% and was higher for untreated patients (46.4% versus 23.5%) and for patients in whom clean margins were achieved (51.4% versus 12.5%). The survival time for patients who died of disease was 9 months for squamous cell carcinoma and 38 months for adenoid-cystic carcinoma. All patients experienced anesthesia in the territory of the resected trigeminal branches, but their pain vanished, and their quality of life improved. Lateral skull base surgery may achieve satisfactory oncologic results for patients with low-grade tumors, with improved quality of life for almost all patients.

Polymorphisms of Metabolizing Enzymes and Susceptibility to Ethmoid Intestinal-type Adenocarcinoma in Professionally Exposed Patients.

Intestinal-type adenocarcinoma (ITAC) of ethmoid is a rare tumor associated with occupational exposure to wood and leather dusts. Polymorphisms in xenobiotic metabolizing enzymes play an important role in gene-environment interactions and may contribute to a high degree of variance in individual susceptibility to cancer risk. The aim of this study was to investigate by polymerase chain reaction the role of polymorphisms at CYP1A1 and GSTM1 genes in 30 ethmoid ITAC patients and 79 healthy donors. The distribution of Thr/Asn genotype at CYP1A1 codon 461 was significantly overrepresented among the patients (23.3%; P = .0422), whereas the Ile/Val genotype at CYP1A1 codon 462 was not significantly different between cases and controls (P = .76). The GSTM1 null genotype was not significantly different between cases and control (P = 1), but we observed that the combined codon 461 Thr/Asn and GSTM1 null genotype was overrepresented in the patient group (P = .0019). The results reveal that patients with CYP1A1 codon 461 polymorphism may be at high genetic risk of ITAC and that the risk increases in the presence of combined polymorphism of CYP1A1 and GSTM1 null genotype. This strongly suggests that CYP1A1 codon 461 and GSTM1 null genotype may be useful in selecting exposed individuals at risk for ethmoid ITAC.

Craniofacial resection for malignant tumours involving the anterior skull base.

Ethmoid malignant tumours are rare, but nearly all at least approach or involve the lamina cribrosa. An anterior craniofacial resection is almost always mandatory for a radical resection. While almost everything has been written about technical details, few studies reported meaningful analysis about prognostic factors and long-term results, for a series of reasons: the infrequency of these tumours, the variety of histologies, small patients cohorts presented by each author, a medley of untreated and pre-treated patients, the lack of a universally accepted classification. We perform a review of the literature in the light of our experience of 330 anterior craniofacial resections for ethmoid malignant tumours. We present our classification of ethmoid malignant tumours (called INT, Istituto Nazionale Tumori). It turned out to be more prognostic than AJCC-UICC classification.

Which classification for ethmoid malignant tumors involving the anterior skull base?

BACKGROUND: The purpose of this study was to compare three systems of classification for malignant ethmoidal tumors in patients undergoing anterior craniofacial resection. METHODS: A radiologic locoregional evaluation of 241 patients with malignant ethmoid tumors was performed before patients underwent an anterior craniofacial resection. Disease in each case was staged according to the American Joint Committee on Cancer-Union Internationale Contre le Cancer (AJCC-UICC) 1997 classification, the AJCC-UICC 2002 classification, and the Istituto Nazionale Tumori (INT) classification. Kaplan-Meier curves and Cox models were used to investigate the prognostic value of each classification system on disease-free survival (DFS) and overall survival (OS). The classifications were compared in terms of prognostic discrimination capability, measured by use of an index of agreement between each classification and DFS or OS time. RESULTS: All three classification systems yielded statistically significant results in the Cox analysis, both for DFS and OS. In the AJCC-UICC 2002 system, minor differences were observed between T1 and T3 tumors. The INT classification showed a progressive worsening of the prognosis with increasing stage. The index of prognostic discrimination favored the INT classification over both the 1997 and 2002 AJCC-UICC classifications. CONCLUSIONS: Both the 1997 and 2002 AJCC-UICC classifications seemed to have limited prognostic value. By contrast, the INT classification satisfied one of the main goals of tumor staging, demonstrating the progressive worsening of prognosis with different tumor classes.