Immunotherapy in head and neck cancers: A new challenge for immunologists, pathologists and clinicians.

Cancer occurrence can be understood as the result of dysfunctions in immune tumoral microenvironment. Here we review the recent understandings of those microenvironment changes, regarding their causes and prognostic significance in head and neck (HN) carcinoma. We will focus on HN squamous cell cancer (SCC) and nasopharyngeal carcinomas (NPC). Their overall poor prognosis may be improved with immunotherapy in a subset of patients, as supported by current clinical trials. However, finding reliable markers of therapeutic response is crucial for patient selection, due to potential severe adverse reactions and high costs. Half of HNSCC exhibit PD-L1 expression, this expression being higher in HPV-positive tumors. In recent clinical trials, a better therapeutic response to anti-PD-1 was obtained in patients with higher PD-L1 expression. The Food and Drug Administration (FDA) approved the use of these therapeutics without stating a need for patient selection regarding PD-L1 status. Activation status, density and localization of TIL as well as PD-L2, γ-interferon, inflammatory cytokines, epithelial-mesenchymal transition phenotype and mutational burden may all be potential therapeutic response markers. In Epstein-Barr Virus (EBV)-induced nasopharyngeal non-keratinizing cancer, PD-L1 is over-expressed compared to EBV-negative tumors. A 22% response rate has been observed under anti-PD-1 treatment among PD-L1-positive NPC patients. A better understanding of immune checkpoint regulation processes may allow patients to benefit from these promising immunotherapies.

Survival and laryngeal preservation tradeoff in advanced laryngeal cancer: From the otorhinolaryngology patient to the managing physician.

BACKGROUND: The purpose of this study was to document the tradeoff between survival and laryngeal preservation in advanced-stage laryngeal cancer amenable to chemoradiation or total laryngectomy. METHODS: We conducted a prospective analysis based on a questionnaire completed by 209 laryngeal cancer specialists and 269 volunteers from an otorhinolaryngology clinic. RESULTS: Of the responders, 34.5% would not consider any decrease in survival to preserve their larynx. This percentage varied from 52% in otorhinolaryngologists to 27.3% in radiotherapists and 28.6% in volunteers (P < .001). Among the responders prepared to trade, the percentage of survival they were willing to trade to preserve their larynx varied from 5% to 100% (median 30%). On univariate analysis, 3 variables significantly affected this percentage: (1) the living status (single or not); (2) the existence of children; and (3) the study group (volunteers, radiation therapists, or otorhinolaryngologists) to whom the responders belong. CONCLUSION: The significant variations noted should develop modes of practice that cater to this and stimulate further research in this field.

Postoperative hemorrhage after transoral oropharyngectomy for cancer of the lateral oropharynx.

OBJECTIVE: Assessment of incidence, risk factors, management, and outcome of postoperative hemorrhage after transoral oropharyngectomy for cancer of the lateral oropharynx. METHODS: Retrospective review of a cohort of 514 cancers of the lateral oropharynx consecutively resected. RESULTS: Incidence of postoperative hemorrhage was 3.6%. In 31.5% of cases, onset was after hospital discharge. No hemorrhages occurred after the end of the fourth postoperative week. Variables associated with increased risk of hemorrhage were advanced age (P=.004), antithrombotic treatment (P=.012), and robotic assistance (P=.009). When the source of hemorrhage could be identified, hemostasis, performed transorally in most cases, was highly effective; no patients in this subgroup showed recurrence. In spontaneously resolved hemorrhage under observation or when no active site of bleeding was found on exploration under general anesthesia, the recurrence rate was 18.1%. Overall, hemorrhage resulted in death in 2 patients. CONCLUSION: Exploration under general anesthesia in case of active bleeding and observation with discussion of arterial exploration of the ipsilateral external carotid system in patients in whom no source of bleeding can be identified are the keys to successful management of this potentially lethal complication.

[Experimental program personalized care in patients with head and neck cancer]. / Expérimentation du parcours personnalisé des patients atteints d'un cancer des voies aéro-digestives supérieures.

OBJECTIVE: Describe the implementation and preliminary results of the "Experimental Program Personalized care" in patients with Head and Neck cancer. MATERIALS AND METHODS: After being selected a graduate nurse status, called coordination, participated in the development of forms of detection needs and concerns of patients, in collaboration with various health professionals. RESULTS: Between January 2011 and December 2012, 200 new patients with head and neck cancer were included: 62% with advanced cancer and 38% of early stage. No patient refused to participate in this experiment. At least one consultation with a psychiatrist was necessary for 82% of patients with advanced cancer. Social problems were the second axis of the needs of patients. CONCLUSION: By identifying the needs of patients and organizing their support, this evaluation optimizes not only the therapeutic care for the patient but also the management of human resources within the team.

[Unilateral laryngeal nerve paralysis in the adult: Epidemiology, symptoms, physiopathology and treatment]. / Paralysies laryngées unilatérales de l'adulte : épidémiologie, symptomatologie, physiopathologie et traitement.

In France, the main causes for unilateral laryngeal nerve paralysis in the adult patient are surgery and malignant tumors. Most of unilateral laryngeal nerve paralysis following thyroid surgery will recover within the first six postoperative months. At the time of unilateral laryngeal nerve paralysis, swallowing impairment and dyspnea occur in around 30% and 5% of cases, respectively. In the face of a unilateral laryngeal nerve paralysis occurring without a history of trauma of surgery, the main paraclinical examination to perform is a computed laryngeal nerve examination analyzing the whole length of the nerve involved. Speech therapy efficiency is related to the degree of severity of the symptoms related to unilateral laryngeal nerve paralysis. In the vast majority of cases, laryngeal medialization approaches improve dysphonia and swallowing impairment related to unilateral laryngeal paralysis, but not dyspnea.

Lateral pharyngotomy for selected invasive squamous cell carcinoma of the lateral oropharynx--part I: how.

OBJECTIVES/HYPOTHESIS: To revisit the surgical technique of lateral pharyngotomy in patients with selected, isolated, and untreated invasive squamous cell carcinoma of the lateral oropharynx. To describe postoperative management, complications, and functional outcomes. STUDY DESIGN: Retrospective review from a French university teaching hospital. METHODS: Ninety-one patients consecutively underwent lateral pharyngotomy for selected T1­T4 squamous cell carcinoma of the lateral oropharynx. RESULTS: Of the patients, 73.6% and 98.9% experienced an uncomplicated surgical and medical postoperative course, respectively. There were no intraoperative deaths, but a single patient died in the immediate postoperative period from carotid rupture following salivary oropharyngeal fistula. The most common significant complications were severe postoperative swallowing impairment, pneumonia from aspiration, and salivary oropharyngeal fistula noted in 6.5%, 4.3%, and 4.3% of cases, respectively. In univariate analysis, none of the variables under analysis was related to the various significant complications noted and/or to immediate postoperative death. No patient had a permanent tracheotomy, whereas one had a permanent gastrostomy. Of the patients in whom a full course of radiation therapy was delivered postoperatively, 13.6% developed a major complication. CONCLUSIONS: From a functional point of view, lateral pharyngotomy is a safe, reliable surgery with few major complications and might be considered a valuable alternative to chemoradiation and/or mandibulotomy for selected tumors of the lateral oropharynx.

Lateral pharyngotomy for selected invasive squamous cell carcinoma of the lateral oropharynx. Part II: when and why.

OBJECTIVES/HYPOTHESIS: To analyze local failure following lateral pharyngotomy for selected untreated invasive squamous cell carcinoma (SCC) of the lateral oropharynx. STUDY DESIGN: Retrospective review from a university teaching hospital. METHODS: Inception cohort of 91 patients who underwent lateral pharyngotomy for an isolated and previously untreated selected invasive carcinoma of the lateral oropharynx classified as T1 (26), T2 (47), T3 (11), and T4 (7). Induction chemotherapy, neck dissection, and postoperative radiation therapy were used in 91.2%, 94.5%, and 53.5% of patients. RESULTS: The 5-year Kaplan-Meier estimate of local failure was 16.6% for T1, 19% for T2, 38.6% for T3, and 16.7% for T4 lesions (P = .46). In a logistic regression model, only positive margins of resection statistically increased (P = .01) the risk for local failure. In patients with safe margins of resection, the 5-year Kaplan-Meier estimate of local failure was 5.6% for T1 lesions, 10.7% for T2 lesions, 23.8% for T3 lesions, and 20% for T4 lesions (P = .4). Local failure had a significant impact on increased nodal failure (P = .001) and on reduced survival (P < .0001). CONCLUSION: The lateral pharyngotomy approach should be viewed as a valuable oncologic alternative to both mandibulotomy and chemoradiation in patients with selected SCC of the lateral oropharynx.

Conventional transoral surgery for stage I-II squamous cell carcinoma of the tonsillar region.

BACKGROUND: The purpose of this study was to review the results of conventional transoral resection and neck dissection for stage I to II squamous carcinoma of the tonsillar region. METHODS: We conducted a retrospective review of 65 patients (stage I, 21 patients; stage II, 44 patients). Induction chemotherapy and postoperative radiation therapy (RT) were administered in 76.9% and 12.3%, respectively, of these cases. RESULTS: The postoperative course was uneventful in 96.9% of patients. Five-year actuarial estimates for local recurrence, nodal recurrence, distant metastasis, and survival were 0% to 7.6%, 0% to 7.8%, 0% to 7.3%, and 70.8% to 71.5% for patients with T1 to T2 carcinoma, respectively. Contralateral and retropharyngeal recurrence occurred in only 1 patient. CONCLUSION: Conventional transoral resection with ipsilateral neck dissection provides an alternative approach for patients with stage I to II squamous cell carcinoma (SCC) of the tonsillar region. A primary surgical approach spares the use of radiotherapy to eliminate late effects and to permit its use for subsequent management of metachronous head and neck second primary cancer.

Lack of adverse events after medialization laryngoplasty With the montgomery thyroplasty implant in patients with unilateral laryngeal nerve paralysis.

OBJECTIVES: We sought to document the incidence of and risk factors for adverse events after medialization laryngoplasty with Montgomery implant insertion in patients with unilateral laryngeal nerve paralysis. METHODS: We studied a retrospective series of 191 patients consecutively managed at a university teaching hospital. RESULTS: No adverse events were noted in 79.8% of the patients. Intraoperative, immediate, and late postoperative adverse events were noted in 8.3%, 8.9%, and 4.1% of the patients, respectively. The various adverse events noted were failure to insert the implant (3.6%), difficulties in stabilizing the implant (4.8%), misplacement of the implant (2.1%), dyspnea (2.7%), hematoma (4.8%), extrusion (1.6%), persistent morphological laryngeal alterations (1.6%), and keloid scars (1.1%). Tracheotomy, procedure-related death, and infection at the insertion site were not encountered. No significant statistical relationship was noted between the various adverse events encountered and the variables under analysis. CONCLUSIONS: Our data demonstrate that medialization laryngoplasty with Montgomery implant insertion in patients with unilateral laryngeal nerve paralysis from various causes is a relatively safe, reliable, and reproducible procedure with a short learning curve.

Trade-off between survival and laryngeal preservation in advanced laryngeal cancer: the otorhinolaryngology patient's perspective.

OBJECTIVES: We performed a prospective study to evaluate, from the patient's perspective, the trade-off between speech and survival that individuals face when given a diagnosis of advanced-stage laryngeal cancer amenable to either total laryngectomy or a laryngeal preservation protocol using chemotherapy and radiotherapy. METHODS: Volunteers (309) consecutively seen at the otorhinolaryngology clinic of a university teaching hospital in France completed an anonymous questionnaire designed to determine their position if they faced the diagnosis of an advanced-stage laryngeal cancer. Univariate analysis was performed for potential statistical relationships with various variables. RESULTS: We found that 12.9% of patients were unable to determine their position regarding the two treatment options offered, and this group had a significant statistical relationship with four variables (age, education, professional status, and history of cancer among relatives). We found that 24.6% of patients made survival their main consideration and would not consider any trade-off. Among the 62.5% who considered the trade-off, the percentage of cure that patients were ready to lose in order to preserve their larynx varied from 5% to 100% (mean, 33%; SD, 23%). Aside from the undecided group, none of the variables analyzed was related either to the decision as to whether to consider a trade-off or to the percentage of c re that patients agreed to trade to preserve their larynx. CONCLUSIONS: In patients with advanced-stage laryngeal cancer, treatment should be initiated only after careful evaluation of the patient's attitude toward both laryngeal preservation and survival.

[Unilateral laryngeal paralysis in the adult patient]. / Paralysies laryngées unilatérales de l'adulte.

Based on a review of the recent medical literature, the authors document the epidemiological evolution, pathophysisology diagnosis and recent advances in treatment for adult patients with unilateral laryngeal paralysis. Speech therapy, which used to be the only therapeutic option, is nowadays complemented by efficient surgical techniques, which have modified the management of many patients.

Early unilateral laryngeal paralysis after pulmonary resection with mediastinal dissection for cancer.

BACKGROUND: The purpose of this study was to document the symptoms, evolution, management, and outcome in a large series of patients with an early unilateral laryngeal paralysis after mediastinal lymph node dissection and pulmonary resection for cancer. METHODS: In this retrospective series of 69 patients, treatment relied on isolated speech therapy in 18 patients and surgical medialization of the paralyzed vocal cord in 51 patients. Duration of follow-up varied from 2 to 109 months, with a mean duration of 15 months. Treatment included isolated speech therapy and laryngeal medialization in 18 patients and 51 patients, respectively. RESULTS: Symptoms included swallowing impairment and dysphonia noted in 63.7% and 98.5% of patients, respectively. Recovery of motion of the paralyzed larynx varied from 2.8% in patients in whom the operative report mentioned that the inferior laryngeal or Xth cranial nerve had been transected, to 23.5% in patients in whom the operative report did not mention nerve transection. Recovery of motion did not occur past the ninth month that followed thoracic surgery. When performed, medialization of the paralyzed larynx resulted in an overall 95.4% and 96% improvement rate for swallowing impairment and dysphonia, respectively, but 1 patient also died of aspiration-related pneumonia. CONCLUSIONS: In patients with an early unilateral laryngeal paralysis after pulmonary resection with mediastinal lymph node dissection for cancer, laryngeal medialization has a beneficial impact on swallowing, speech, and voice, resulting in a better quality of life. Persistent swallowing impairment after laryngeal medialization must be managed aggressively, given the risk for delayed pneumonia and even death from aspiration.

Extended lateral pharyngotomy for selected squamous cell carcinomas of the lateral tongue base.

OBJECTIVES: In a retrospective review of an inception cohort of 26 patients with an isolated, previously untreated, moderately to well-differentiated invasive squamous cell carcinoma of the lateral tongue base, consecutively managed with an extended lateral pharyngotomy approach at a single tertiary referral care center, the authors review the key surgical points, highlight the potential technical pitfalls, and document the complications and long-term functional and oncological outcomes in terms of survival and local control. METHODS: The adjunctive measures included induction chemotherapy, ipsilateral neck dissection, and postoperative radiotherapy, used in 96.1%, 96.1%, and 38.5% of patients, respectively. All patients but 2 were followed for at least 5 years or until death (maximum, 158 months). RESULTS: The significant postoperative complications included pharyngocutaneous fistula in 3 patients (11.5%) and hemorrhage requiring reoperation, partial flap necrosis, and pneumonia from aspiration in 1 patient (3.8%) each. In univariate analysis, no significant statistical relationship was noted between the significant postoperative complications noted and the variables under analysis. Overall, successful oral alimentation was achieved in 100% of patients by the first postoperative month without gastrostomy, tracheotomy, or completion total laryngectomy. There were no intraoperative or perioperative deaths. The main causes of death were metachronous second primary tumor, intercurrent disease, and distant metastasis, resulting in 84.6%, 64%, and 46.9% 1-, 3-, and 5-year Kaplan-Meier actuarial survival estimates, respectively. Two patients (7.6%) had local recurrence, resulting in 100%, 86.7%, and 86.7% 1-, 3-, and 5-year Kaplan-Meier actuarial local control estimates, respectively. As a function of T stage, the 3- and 5-year actuarial local control estimates were 100%, 87.5%, and 90.9% in patients with tumors classified as T1, T2, and T3-T4a, respectively. CONCLUSIONS: Such results suggest that extended lateral pharyngotomy should be integrated among the various conservative treatment options available to patients with selected carcinomas of the lateral tongue base.

Horizontal supraglottic partial laryngectomy for selected squamous carcinoma of the vallecula.

BACKGROUND: Our aim was to determine the incidence of local control in patients with selected squamous carcinoma of the vallecula treated with horizontal supraglottic laryngectomy; to analyze the consequences of local recurrence in terms of nodal recurrence, distant metastasis, survival, causes of death, overall local control, and laryngeal preservation; and to identify any clinical factors predictive of these outcomes. METHODS: This was a retrospective nonrandomized case series in a university teaching hospital. An inception cohort of 95 previously untreated patients were followed until death or for a minimum of 5 years. According to the 2002 Union Internationale Contre le Cancer (UICC) staging classification system, the tumor was classified as T1, T2, and T3 in 13, 60, and 22 patients, respectively, while disease in 67 patients was considered to be in stages III to IV. All patients underwent a horizontal partial supraglottic partial laryngectomy. Ninety-four patients had an associated neck dissection. An induction chemotherapy regimen was used in 91 patients; postoperative radiation therapy was given for 49 patients. The main outcome measures were local recurrence, nodal recurrence, distant metastasis, and survival. RESULTS: The 1-, 3-, and the 5-year actuarial survival estimates were 86.3%, 64.2%, and 47.4%, respectively. Overall, the main causes of death were as follows: metachronous second primary tumor (47.2% of patients), intercurrent disease (16.7%), distant metastasis (15.3%), local recurrence (6.3%), and nodal recurrence, (4.2%). The 1-, 3-, and 5-year actuarial local recurrence rates were 4.5%, 11%, and 11%, respectively. Nine patients developed a local recurrence; 3 were successfully salvaged. Using multivariate analysis, no single variable was found to increase the risk for local recurrence. The overall laryngeal preservation rate and local control rate were 89.5% (85/95) and 93.4% (89/95), respectively. Local recurrence was associated with a significant increase in nodal recurrence (p <.04) and distant metastasis (p = .03). CONCLUSIONS: Based on this experience, horizontal partial supraglottic laryngectomy appears to be a valid approach for functional organ-preservation in patients with selected T1-T3 SCC of the vallecula.

Asymmetric syntheses of 1-aryl-2,2,2-trifluoroethylamines via diastereoselective 1,2-addition of arylmetals to 2-methyl-N-(2,2,2-trifluoroethylidene)propane-2-sulfinamide.

Condensation of N-tert-butanesulfinamide (S)-1 with trifluoroacetaldehyde hydrate 2a afforded 2-methyl-N-(2,2,2-trifluoroethylidene)propane-2-sulfinamide 3. Without isolation and purification, imine 3 was added to various aryllithium reagents to give highly diastereomerically enriched adducts 5a-g. Acidic methanolysis of 5a-g provided the desired 1-aryl-2,2,2-trifluoroethylamine hydrochloride compounds 6a-g. [reaction: see text].

Sternocleidomastoid myofascial flap for reconstruction after composite resection of invasive squamous cell carcinoma of the tonsillar region: technique and outcome.

OBJECTIVE: To present the surgical technique and determine the efficacy of sternocleidomastoid myofascial (SCMF) flap reconstruction after composite resection with intent to cure. STUDY DESIGN: Retrospective review of 73 consecutive patients with a previously isolated and untreated moderately to well-differentiated invasive squamous cell carcinoma of the tonsillar region and a minimum of 3 years follow-up, managed at a tertiary referral care center during the years 1970 to 2002, with an ipsilateral superiorly based SCMF flap after composite resection. METHODS: The surgical procedure is presented in detail. Potential technical pitfalls are highlighted. Survival, mortality, and morbidity are documented. Univariate analysis for potential correlation between the incidence for postoperative flap complications and various variables is also performed. RESULTS: The 1, 3, and 5 year Kaplan-Meier actuarial survival estimates were 82.2%, 64.4%, and 49.3%, respectively. Death never appeared to be related to the completion of the SCMF flap. Thirty-three (45.2%) patients had some kind of significant postoperative surgical complication, and nine (12.3%) patients had some kind of significant postoperative medical complication. The most common significant postoperative complication was partial SCMF flap necrosis and pharyngocutaneous fistula noted in 30.1% and 10.9% of patients, respectively. Complete SCMF flap necrosis was never encountered. No patient developed carotid artery rupture or died as a result of the SCMF flap, and none required additional surgery. In univariate analysis, no significant statistical relation was noted between the significant postoperative surgical complications related to the use of the SCMF flap and the variables under analysis. CONCLUSIONS: The superiorly based SCMF flap appears to be simple to perform and useful for reconstruction of defects after composite resection.

Resection of selected invasive squamous cell carcinoma of the pyriform sinus by means of the lateral pharyngotomy approach: the partial lateral pharyngectomy.

BACKGROUND: Although the lateral pharyngotomy is a well-known surgical procedure, to our knowledge, no published reports have described the results achieved with a lateral pharyngectomy approach in patients with isolated and previously untreated selected invasive squamous cell carcinoma of the lateral wall of the pyriform sinus. METHODS: The medical files and operative charts of 30 patients with an isolated, and previously untreated, squamous cell carcinoma of the pyriform sinus, treated for cure by lateral partial pharyngectomy and primary closure, as well as postoperative radiotherapy (n = 22), and preoperative chemotherapy (n = 8), were retrospectively studied. Sixteen tumors were classified as T1 and 14 as T2. All patients but one were followed until death. RESULTS: Three patients (9%) died in the immediate postoperative period (two from medical complications and one from a surgery-related complication). Overall, 29 patients died, resulting in a 77.7%, 40%, 23.3%, and 15% 1-, 3-, 5- and 10-year Kaplan-Meier actuarial survival estimate, respectively. Only one patient had a serious postoperative complication develop. All patients were decannulated. No patients required a gastrostomy and/or completion total laryngectomy for functional reasons. Local recurrence occurred in four patients (13%). The 3-and 5-year Kaplan-Meier actuarial local control estimates were 88.5% and 79.6%, respectively. The use of a platin-based induction chemotherapy (p = .05) regimen was the only variable that was significantly statistically related to local recurrence. Overall, a 93.3% laryngeal preservation rate was achieved. CONCLUSION: Partial pharyngectomy by means of the lateral pharyngotomy combined with postoperative radiation therapy is an efficient and function-sparing approach to control selected invasive squamous cell carcinomas of the lateral wall of the pyriform sinus.

Thyroplasty type I with Montgomery implant among native French language speakers with unilateral laryngeal nerve paralysis.

OBJECTIVE: To document the long-term results achieved with the Montgomery implant in 96 French speakers with a unilateral laryngeal nerve paralysis (ULNP). STUDY DESIGN: Retrospective series, inception cohort of 96 patients. METHODS: Data regarding morbidity and functional results were obtained at regular visits to our clinic. All patients were followed for a minimum of 6 months or until death. Forty-two patients had a minimum of 12 months of follow-up. Early in the study, 36 patients were prospectively recorded under similar conditions before placement of the Montgomery implant and at 1, 3, 6, and 12 months postoperatively. RESULTS: None of the 96 patients died in the immediate postoperative period. The perioperative course was unremarkable in 94.8% of cases. Perioperative problems included failure to obtain a satisfactory phonatory result in three patients, difficulty to stabilize the implant posteriorly in one patient, and fracture of the inferior rim of the thyroid cartilage window in another patient. The primary immediate postoperative problem (within the first postoperative month) was laryngeal dyspnea, noted in four patients. According to the patient's subjective assessment, speech and voice was always improved in the immediate postoperative period. However, three patients had secondary degradation of speech and voice. Revision surgery under local anesthesia resulted in a 97.9% ultimate speech and voice success rate. According to the patient's subjective assessment, adequate swallowing in the immediate postoperative period was achieved in 94.2% of cases that had swallowing problems preoperatively. A significant statistical increase in the duration parameters (phonation time, phrase grouping, speech rate) together with a statistical significant decrease in both the jitter and shimmer values was noted when comparing the preoperative and the postoperative values at 1 month. Analysis of the evolution of the speech and voice parameters at 1, 3, 6, and 12 months postoperatively showed a significant decrease in the fundamental frequency and noise-to-harmonic ratio values but did not demonstrate any significant differences for the other speech and voice parameters. CONCLUSIONS: From the reported data, we conclude that the type I thyroplasty with Montgomery implant insertion is a safe and reproducible method to treat ULNP. Furthermore, this system achieves very good and stable phonatory results. Finally, the use of this technique and implant system appears safe in patients from various cultures with ULNP from a variety of causes and severe comorbidity. Over the past decade at our department, this procedure progressively replaced the use of the intracordal injection of autologous fat injection that was initially advocated in patients with ULNP.