Search

Simple Summary: This retrospective study is the first attempt to investigate the tumor–stroma ratio in a series of laryngeal basaloid squamous cell carcinomas (SCCs), comparing them with a group of stage-matched conventional SCCs, in both preoperative and surgical specimens. This study's aim was to ascertain the biological aggressiveness of laryngeal basaloid SCCs and to investigate any possible role of stromal-related features in such a clinical behavior. The tumor–stroma ratio, evaluated in laryngeal biopsies and in the entire excised tumor, displayed a prognostic effect in terms of reduced disease-free survival in conventional SCC cases but not in basaloid ones. Basaloid squamous cell carcinoma (BSCC) is a subtype of squamous cell carcinoma (SCC) associated with a poor prognosis. Tumor–stroma ratio (TSR) has been introduced as a prognostic feature in many solid tumors. TSR was investigated in a series of laryngeal BSCCs and compared with a group of stage-matched conventional SCCs (cSCCs), in both preoperative and surgical specimens, with the intent of ascertaining the more aggressive behavior of BSCC and verifying the presence of stromal-related causes. A series of 14 consecutive laryngeal BSCCs and a control group of 28 stage-matched conventional cSCCs were analyzed. A higher nodal metastasis presence was found in BSCCs (57.1% vs. 28.6%). The recurrence rate was 33.5% and 63.6% in the cSCC and BSCC groups; disease-free survival (DFS) was higher, though not significantly, in patients with cSCC. TSR, large cell nests, and tumor budding showed a moderate to very good agreement, and stroma type a good to very good agreement between biopsies and surgical specimens in the cSCC group. In the BSCC group, agreement was poor to very good for TSR and stroma type, and good to very good for large cell nests and tumor budding. Age was the only feature significant in predicting recurrence in the BSCC group (p = 0.0235). In cSCC, TSR low/stroma rich cases, when evaluated on biopsies or surgical specimens, were associated with lower DFS (p = 0.0036; p = 0.0041, respectively). Laryngeal BSCCs showed a lower DFS than cSCCs, even if statistical significance was not reached. TSR, evaluated in laryngeal biopsies and excised tumors, was prognostic in terms of DFS in cSCC but not in BSCC cases. [ABSTRACT FROM AUTHOR]

Glottic squamous cell carcinoma (SCC) in stages I or II can be treated by transoral CO2 laser microsurgery (TLM) or exclusive radiotherapy (RT). To compare the oncological results of patients treated with TLM, to those treated with RT, in a tertiary hospital. Data from patients diagnosed with glottic SCC in stages I and II between 2004 and 2018 were analyzed. Response to treatment was studied in terms of recurrence, local control and laryngeal preservation. Of 164 patients, 63.41% received treatment with TLM and 36.58% with RT. 26.21% presented a recurrence or progression of the tumor. Both treatments obtained good local control rates (84.15% in the case of TLM and 89.6% in the case of RT) and no significant association was found between tumor recurrence and type of treatment, nor with the involvement of the anterior commissure. However, treatment with RT obtained worse laryngeal preservation rate compared to TLM (81.6% and 100% respectively) (p <.001LR). Conclusions and significance: Both treatments obtained good oncological results. There were no significant differences regarding local control. However, TLM obtained a better laryngeal preservation rate. The involvement of the anterior commissure was not a poor prognosis factor for tumor recurrence. [ABSTRACT FROM AUTHOR]

Background: Thyroid gland involvement and invasion during larynx and hypopharynx cancers is rare, but due to the anatomical closeness of the thyroid gland and the larynx, it could occur through local invasion. Thyroidectomy is usually performed in patients with thyroid gland involvement having larynx and hypopharyngeal cancers. A lot of controversies exist regarding the thyroid gland involvement and efficiency of a different kind of thyroidectomy intraoperatively in these types of cancers. Objectives: Thus, elucidating the exact role of thyroidectomy, its efficiency, and parameters associated with thyroid gland involvement is critical in treating the patients with the larynx and hypopharyngeal cancers. Methods: In this retrospective study, the medical records of 117 patients admitted to Loghman Hakim Hospital from 2001 to 2015 with laryngeal and hypopharyngeal carcinoma, who underwent laryngectomy with or without thyroidectomy as a primary treatment of cancer, were evaluated. Several parameters, including gender, prevalence, location of the thyroid gland and lymph node involvement, the exact type of malignancy, differentiation stage of the tumor cells, the exact method of thyroidectomy, thyroid function, and its post-surgical cancer recurrence were assessed. Results: The prevalence of laryngeal cancers was significantly higher in males than females and most of the malignancies were squamous cell carcinoma (SCC). The location of the malignancy was mostly at supraglottis, glottis, transglottis, and subglottis, respectively. The rate of thyroid gland involvement was approximately 11.96%. Lobectomy was performed in 57.14 %, total thyroidectomy was performed in 35.71 %, and in 7.14% of the patients, and thyroidectomy was not performed. After the initial surgery, out of 11.96% of all patients with thyroid gland involvement, 28.5% had a recurrence of the thyroid gland. Only 21% of the patients with thyroid gland involvement had hypothyroidism after the surgery. Conclusions: The rate of thyroid gland involvement in the pathology report after surgery was approximately 3.41% of the thyroid gland involvement, which is low. We concluded that thyroidectomy is a very efficient way, but it should be limited to cases of subglottic or transglobic involvement or in cases of bilateral tumors, high staging, post-cricoid involvement, and clear radiological evidence or in the event of muscle involvement. [ABSTRACT FROM AUTHOR]

Purpose: Early-stage glottic larynx squamous cell carcinoma (GLC) is a relatively common disease with excellent oncologic control, but treatment is associated with acute dysphagia and long-term voice quality changes. This phase 1 study of hypofractionated radiation therapy for early-stage GLC increased the fraction size while reducing the number of fractions until 5-fraction stereotactic ablative radiation therapy (SABR) was delivered.Methods and Materials: Eligible patients had received a diagnosis of stage Tis to T2 GLC. Patients who had undergone prior curative-intent surgery were excluded. The equipotent dose levels were as follows: (1) level 0, 50 Gy in 15 fractions (n = 4); (2) level 1, 45 Gy in 10 fractions (n = 13); and (3) level 2, 42.5 Gy in 5 fractions (SABR level, n = 12). Grade 3 or 4 laryngeal edema, voice, dyspnea, stridor, or cough were the predefined dose-limiting toxicities.Results: Twenty-nine patients were enrolled from November 2013 to March 2017. The median and minimum follow-up times were 39.2 and 13 months, respectively. Two actively smoking patients, 1 treated in level 1 (grade 4 laryngeal edema, grade 3 dysphagia) and 1 treated in level 2 (grade 3 laryngeal necrosis, dysphagia), developed dose-limiting toxicities. The former patient soon developed a local recurrence, and the latter patient recovered. There were a total of 5 local recurrences: 2 in level 0 and 3 in level 1. The Voice Handicap Index results showed robust long-term voice quality with median values of 7 and 0 at 6 and 12 months, respectively.Conclusions: Given the tolerability, excellent voice outcomes, and preliminary efficacy data of 5-fraction glottic larynx SABR, this regimen warrants further study. [ABSTRACT FROM AUTHOR]

Objectives: Laryngeal squamous cell carcinoma (LSCC) can involve different anatomic subunits with peculiar surgical and prognostic implications. Despite conflicting outcomes for the same stage of disease, the current staging system considers different lesions in a single cluster. The aim of this study was to critically discuss clinical and pathologic staging of primary and recurrent advanced LSCC in order to define current staging pitfalls that impede a precise and tailored treatment strategy. Methods: Thirty patients who underwent total laryngectomy in the past 3 years for primary and recurrent advanced squamous cell LSCC were analyzed, comparing endoscopic, imaging, and pathologic findings. Involvement of the different laryngeal subunits, vocal-fold motility, and spreading pattern of the tumor were blindly analyzed. The diagnostic accuracy and differences between clinicoradiologic and pathologic findings were studied with standard statistical analysis. Results: Discordant staging was performed in 10% of patients, and thyroid and arytenoid cartilage were the major diagnostic pitfalls. Microscopic arytenoid involvement was significantly more present in case of vocal-fold fixation (P = .028). Upstaging was influenced by paraglottic and pre-epiglottic space cancer involvement, posterior commissure, subglottic region, arytenoid cartilage, and penetration of thyroid cartilage; on the contrary, involvement of the inner cortex or extralaryngeal spread tended to be down-staged. Radiation-failed tumors less frequently involved the posterior third of the paraglottic space (P = .022) and showed a significantly worse pattern of invasion (P < .001). Conclusions: Even with the most recent technologies, 1 in 10 patients with advanced LSCC in this case series was differently staged on clinical examination, with cartilage involvement representing the main diagnostic pitfall. [ABSTRACT FROM AUTHOR]

Introduction: The concept of neck dissection (ND) in the management armamentarium of head and neck squamous cell carcinoma has evolved throughout the years. Nowadays, ND becomes more functional.Methodology: A retrospective study of 865 patients was performed at Netherlands Cancer Institute-Antoni Van Leeuwenhoek Hospital to investigate the feasibility of selective ND (SND). All patients with squamous cell carcinoma of the pharynx and larynx who received primary radiation and underwent salvage ND were included in the study.Result: A total of 29 NDs were analyzed. In 17 neck sides, viable metastases were found (58%), whereas in the other 12 specimens there were no viable metastases. In 16 of the 17 necks (94%), the metastases were located either in level II, III, or IV or in a combination of these 3 levels. Level V was involved in only 1 case (6%).Conclusion: It is well justified to perform a salvage SND (levels II, III, and IV) for pharyngeal and laryngeal carcinoma after primary radiation. In carefully selected cases of supraglottic and oropharyngeal carcinoma, a superselective ND also appears as an efficient option. [ABSTRACT FROM AUTHOR]

Introduction: It is estimated that around 10% of all head and neck cancer patients in India are aged over 70 years. Elderly patients are often subjected to palliative or inadequate treatment for head and neck cancers in spite of being candidates for curative intent therapy. In this study we evaluated our use of radical radiotherapy in carcinoma larynx for patients over seventy years of age to determine morbidity, likelihood of completing therapy, functional and oncological outcomes.Materials and Methods: 132 patients of squamous cell carcinoma of the larynx treated between 2005-2015 at Amrita Institute of Medical Sciences, Kochi who were seventy years of age or older were included. The endpoint for analysis was overall survival. Survival curves were generated using Kaplan Meier method and univariable analysis was performed using log rank test.Results: The median age of patients was 77 years (range 70-102). All patients (100%) completed radiotherapy with 6 (5%) requiring treatment breaks. All patients had at least minor (grade I/II) toxicities. Grade III toxicities were seen in 10 (8%) of patients. No grade IV reactions or treatment related deaths occurred. When a univariate analysis was performed for determinants of major toxicities with age range, performance status, smoking, number of co-morbidities or TNM stage, no determinants were statistically significant. 2-year disease free survival for stage I, II, III and IV was 100%, 98%, 80% and 64% respectively, and the 2-year overall survival for all four stages was 100%.Conclusion: Patients over seventy years tolerate radical radiotherapy for treatment of laryngeal cancer. In spite of minor toxicities, all patients completed treatment and had good oncological outcomes. Patients with stage III/IV unfit for concomitant chemotherapy administration treated with radiotherapy alone had a good disease free survival. Curative intent therapy should not be withheld from elderly patients on the basis of age. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to report the post-surgical and oncologic outcomes of patients who underwent supracricoid partial laryngectomy (SCPL). Methods: 90 patients who underwent SCPL between 1994 and 2014 were reviewed. 45 patients underwent cricohyoidopexy (CHP) and 45 patients cricohyoidoepiglottopexy (CHEP). Median nasogastric (NG) tube removal time, decannulation time, overall survival, disease-free survival and local control rates were calculated. The effect of the type of surgery on functional and oncologic outcomes were assessed. Results: Median NG tube removal time was 16.5 days (IQR = 10) and 14 days (IQR = 9) in CHP and CHEP patients, respectively (p > 0.05). Median decannulation time was 30 days (IQR = 26) and 19 days (IQR = 15) in CHP and CHEP patients, respectively (p < 0.05). Resection of one arytenoid significantly increased NG tube removal time. Median follow-up time was 55 months. There were 15 oncologic failures and the median time interval for tumor recurrence was 9 months. Five-year overall survival rate was 80.4%. The 3- and 5-year disease-free specific survival rates were 81.7 and 76.7%, respectively. Conclusions: Given the more extensive surgery applied for CHP, functional outcomes were better in patients with CHEP. Resection of an arytenoid had a negative outcome on swallowing. [ABSTRACT FROM AUTHOR]

Conclusion: The degree of midline crossing of lateral supraglottic cancer does not significantly change its rate of contralateral cervical metastasis. The rate of occult metastasis is too high to take the risk of contralateral regional recurrence. We support routine bilateral neck dissection even in lateral supraglottic cancers with no or minimal midline crossing. Objectives: Data on the rate of contralateral cervical metastasis of laterally located supraglottic cancer, the effect of its degree of midline crossing on contralateral cervical metastasis, and its treatment are still controversial. Methods: This was a retrospective cohort, chart review involving 305 surgically treated patients with T1-3 squamous cell carcinoma of the supraglottic larynx. In all, 184 patients had bilateral neck dissection; 86 N0 contralateral necks were followed up. Thirty-five patients who needed postoperative radiation therapy because of the primary tumor or ipsilateral neck dissection specimen also received radiation therapy to the contralateral neck. The degree of midline crossing at the epiglottis was measured on a laryngectomy specimen with a ruler and expressed as 'no,' '<5 mm' or '≥5 mm.' Results: The rates of occult and overall contralateral metastasis in our series were 16% and 28%, respectively. There was no statistically significant difference between contralateral neck metastasis and recurrence rates in the neck dissection, follow-up, and irradiation groups according to the degree of midline crossing. [ABSTRACT FROM AUTHOR]

With the growing acceptance of nonsurgical therapies for laryngeal squamous cell carcinomas (LSCCs), it has become important to delineate surgical salvage strategies for disease recurrences. Total laryngectomy is often recommended, but appropriately selected laryngeal recurrences may be treated successfully with partial laryngeal surgery: laryngeal function can be preserved with oncological efficacy. The main available studies dealing with partial laryngeal surgery in recurrent carcinoma were critically reviewed. The most appealing feature of salvage transoral laser surgery (TLS) is the opportunity to make tumor-tailored excisions without any reconstructive limitations and retaining the option to switch to open partial laryngectomy. A recent detailed review of 11 series found a pooled local control rate of 57% after a first TLS procedure. Supracricoid laryngectomy (SCL) seems to achieve good local control rates in selected cases of recurrent supraglottic-glottic carcinoma: one review considering seven series calculated that 85% of the patients treated with salvage SCL after radiotherapy experienced no local recurrence; and total laryngectomy after failure of salvage SCL afforded an overall local control rate of 65%. Neck dissection is mandatory in all cases of local LSCC recurrence with evidence of neck metastases, and routine elective neck dissection is recommended for recurrent supraglottic and transglottic cancers. [ABSTRACT FROM AUTHOR]

Objectives: The study was intended to compare the outcomes for T1-T2N0M0 glottic squamous cell carcinoma with anterior commissure involvement who had undergone partial laryngectomy (PL) or radiotherapy (RT).Materials and Methods: We retrospectively analyzed 256 patients who were treated by RT (n = 70) or PL (n = 186). Patients received prophylactic irradiation of the neck in RT group whereas PL was not associated with lymphadenectomy. Propensity score matching (PSM) was used to eliminate the baseline variations.Results: The average age of the RT group (67 years) was significantly higher than that of the PL (59 years). Local recurrence was noted in 14 patients of the RT group and 22 of the PL. While regional recurrence was noted in only 1 patient of the RT group and 23 of the PL. After PSM, the 5-year overall survival (82.8% vs. 83.9%, p = 0.302), 5-year cancer-specific survival (88.3% vs. 89.7%, p = 0.793), 5-year local relapse-free survival (79.3% vs. 84.5%, p = 0.127) were not significantly different between two groups. However, 5-year regional relapse-free survival in the RT group was significantly better than that in the PL (100% vs. 87.1%, p = 0.014). In the PL group, infection, granuloma, laryngeal stenosis, chylous leakage, and pharyngeal fistula were reported in six, 11, 12, one, and two patients, respectively.Conclusions: RT resulted in comparable rates of survival, local control, and larynx preservation compared to PL. However, RT was associated with higher regional control rate. The complication rates were extremely low in RT group. [ABSTRACT FROM AUTHOR]

Simple Summary: Organ preservation protocols have become first line therapy for the majority of advanced laryngeal cancers. Unfortunately, up to one third of patients will develop recurrent disease requiring salvage surgery. These tumors tend to display aggressive features when compared to primary disease. The aim of this study is to identify genomic alterations associated with poor prognosis in the recurrent setting to guide precision therapy and identify potential targetable pathways. Here we show that mutations in the oxidation pathway, specifically the KEAP1-NFR2 pathway, predict survival in a cohort of patients undergoing salvage laryngectomy. Organ preservation protocols are commonly used as first line therapy for advanced laryngeal cancer. Recurrence thereafter is associated with poor survival. The aim of this study is to identify genetic alterations associated with survival among patients with recurrent laryngeal cancer undergoing salvage laryngectomy. Sixty-two patients were sequenced using a targeted panel, of which twenty-two also underwent transcriptome sequencing. Alterations were grouped based on biologic pathways and survival outcomes were assessed using Kaplan-Meier analysis and multivariate cox regression. Select pathways were evaluated against The Cancer Genome Atlas (TCGA) data. Patients with mutations in the Oxidation pathway had significantly worse five-year disease specific survival (1% vs. 76%, p = 0.02), while mutations in the HN-Immunity pathway were associated with improved five-year disease specific survival (100% vs. 62%, p = 0.02). Multivariate analysis showed mutations in the Oxidation pathway remained an independent predictor of disease specific survival (HR 3.2, 95% CI 1.1–9.2, p = 0.03). Transcriptome analysis of recurrent tumors demonstrated that alterations in the Oxidation pathway were associated a positive Ragnum hypoxia signature score, consistent with enhanced pathway activity. Further, TCGA analyses demonstrated the prognostic value of oxidation pathway alterations in previously untreated disease. Alterations in the Oxidation pathway are associated with survival among patients with recurrent laryngeal cancer. These prognostic genetic biomarkers may inform precision medicine protocols and identify putatively targetable pathways to improve survival in this cohort. [ABSTRACT FROM AUTHOR]

Aberrant SRC expression and activation is frequently detected in multiple cancers, and hence, targeting SRC has emerged as a promising therapeutic strategy. Different SRC inhibitors have demonstrated potent anti-tumor activity in preclinical models, although they largely lack clinical efficacy as monotherapy in late-stage solid tumors, including head and neck squamous cell carcinomas (HNSCC). Adequate selection and stratification of patients who may respond to and benefit from anti-SRC therapies is therefore needed to guide clinical trials and treatment efficacy. This study investigates the prognostic significance of active SRC expression in a homogeneous cohort of 122 human papillomavirus (HPV)-negative, surgically treated HNSCC patients. Immunohistochemical evaluation of the active form of SRC by means of anti-SRC Clone 28 monoclonal antibody was specifically performed and subsequently correlated with clinical data. The expression of p-SRC (Tyr419), total SRC, and downstream SRC effectors was also analyzed. Our results uncovered striking differences in the prognostic relevance of SRC expression in HNSCC patients depending on the tumor site. Active SRC expression was found to significantly associate with advanced disease stages, presence of lymph node metastasis, and tumor recurrences in patients with laryngeal tumors, but not in the pharyngeal subgroup. Multivariate Cox analysis further revealed active SRC expression as an independent predictor of cancer-specific mortality in patients with laryngeal carcinomas. Concordantly, expression of p-SRC (Tyr419) and the SRC substrates focal adhesion kinase (FAK) and the Arf GTPase-activating protein ASAP1 also showed specific associations with poor prognosis in the larynx. These findings could have important implications in ongoing Src family kinase (SFK)-based clinical trials, as these new criteria could help to improve patient selection and develop biomarker-stratified trials. [ABSTRACT FROM AUTHOR]