Evaluation of the efficacy of immunotherapy for non-resectable mucosal melanoma.

BACKGROUND: Immune checkpoint inhibitors are now standard-of-care treatments for metastatic cutaneous melanoma. However, for rare sub-groups, such as mucosal melanomas, few published data are available, and with no established therapeutic guidelines. Our objective was to assess the response to anti-CTLA4 and anti-PD1 immunotherapy in patients with mucosal melanomas. METHODS: We performed a single-center, prospective cohort analysis of patients with non-surgical locally advanced and/or metastatic mucosal melanoma receiving anti-CTLA4 and/or anti-PD1 immunotherapy from 2010 to 2016. RESULTS: Forty-four patients were enrolled, including 18 (40.9%) with head and neck, 12 (27.3%) with vulvo-vaginal and 14 (31.8%) with ano-rectal primary tumours. Eleven (25%) patients had stage 3 disease, and 11 (25%) had distant metastases. The first-line immunotherapy was ipilimumab in 24 patients and pembrolizumab in 20. The objective response rate (ORR) was 8.2% (one complete response) for ipilimumab and 35% (four complete responses) for pembrolizumab. No significant difference was observed for primary tumour location. The median follow-up was 24 months (range 4-73). The median progression-free survival (PFS) in the first-line ipilimumab and pembrolizumab groups was 3 months [95% confidence interval (CI) 2.5-4.6] and 5 months (95% CI 2.6-33.1), respectively (p = 0.0147). CONCLUSION: In the patients with unresectable and/or metastatic mucosal melanoma, we found ORR and PFS rates comparable to those in patients with cutaneous melanoma, with no significant differences in the types of mucosal surfaces involved. Anti-PD1 therapy has a more favorable benefit-risk ratio than ipilimumab and should be used preferentially.

Laser debulking or tracheotomy in airway management prior to total laryngectomy for T4a laryngeal cancer.

PURPOSE: Retrospective studies have shown that tracheotomy prior to total laryngectomy (TL) is associated with decreased survival. We sought to investigate whether this is due to higher local invasiveness associated with obstructive disease or whether it is the result of tracheotomy itself. METHODS: We reviewed patients with a T4a (AJCC 7th edition) laryngeal squamous-cell carcinoma treated with a primary TL followed by adjuvant radiotherapy between 2001 and 2013. We compared patients who had obstructive lesions with those who had non-obstructive lesions in terms of preoperative data, pathological features, and treatment outcomes. Second, we compared tracheotomized patients with patients who underwent endoscopic laser debulking (ELD). RESULTS: One hundred patients were reviewed. Thirty-seven of them required an airway intervention prior to a TL (tracheotomy n = 24/ELD n = 13). Patients with obstructive tumors had more frequently subglottic extension (p = 0.0066) and a shorter disease-free survival (DFS) (p = 0.046), due to a higher incidence of additional distant metastases. Tracheotomy was associated with a shorter DFS (p = 0.035) and more frequent perineural invasion (p = 0.0272) as compared to ELD, but not with a higher incidence of stomal recurrence. CONCLUSIONS: A tracheotomy prior to a total laryngectomy is associated with decreased survival. We recommend laser debulking as the preferred treatment whenever management of an obstructive airway is required prior to a total laryngectomy.

Relationship between the time to locoregional recurrence and survival in laryngeal squamous-cell carcinoma.

To assess the relationship between the locoregional disease-free interval after treatment of the primary tumor and survival after a recurrence in patients with laryngeal carcinoma. We retrospectively investigated patients treated in our Cancer Center for a laryngeal cancer who subsequently developed a locoregional recurrence and were followed up until death. Post-recurrence survival was defined as the time from the locoregional recurrence to death. One hundred and twenty-three patients were included. Median post-recurrence survival was 7 months. The locoregional disease-free interval (LRDFI) after treatment of the primary was weakly correlated with post-recurrence survival (r = 0.210, p = 0.020). A LRDFI cut-off of 12 months was a significant prognostic factor (p = 0.005; median, 5 months, 95% CI: 2.239-6.761, vs 10 months, 95% CI: 7.270-12.730). The time to locoregional recurrence in laryngeal cancer was a prognostic factor correlated with post-recurrence survival. Locoregional failure within the first year after treatment of the primary tumor was associated with an unfavorable prognosis.

Outcomes and prognostic factors for squamous cell carcinoma of the oral tongue in young adults: a single-institution case-matched analysis.

There is controversy regarding prognosis and treatment of young patients with oral cavity cancer compared to their older counterparts. We conducted a retrospective case-matched analysis of all adult patients younger than 40 years and treated at our institution for a squamous cell carcinoma of the oral cavity. Only non-metastatic adult patients (age >18) with oral tongue cancer were eventually included and matched 1:1 with patients over 40 years of age, at least 20 years older than the cases, with same T and N category and treatment period. Sixty-three patients younger than 40 had an oral cavity squamous cell cancer out of which 57 had an oral tongue primary during the period 1999-2012, and 50 could be matched with an older control. No difference could be seen between younger and older patients with regard to overall, cancer-specific, or progression-free survival. The patterns of failure were similar, although in young patients, almost all failures occurred during the first 2 years following treatment. Although overall survival shows a trend toward lower survival in older patients, cancer-specific survival and analysis of pattern failure suggest that disease prognosis is similar between young and older adults with oral tongue cancer. Further work is needed to identify the younger patients with poorer prognosis who overwhelmingly fail during the first year after treatment and could benefit from treatment intensification. Until then, young adults ought to be treated using standard guidelines.

Can Early Dissection of Cervical Lymph Nodes Improve Prognosis in Squamous Cell Carcinomas of the Hard Palate.

Squamous cell carcinomas of the hard palate and maxillary alveolar ridge are rare tumours with a poor prognosis. Lymph node dissection is recommended for tumours with nodal involvement, and is rarely performed in the absence of adenopathy. We report a series of patients with squamous cell carcinomas and evaluate the rate of lymph node invasion and its impact on survival. This is a retrospective study of 72 patients treated for squamous cell carcinoma of the hard palate and maxillary alveolar ridge between January 1, 1998 and December 31, 2008 in two cancer centres. Using clinical and radiological assessment, tumours were classified as T1-T2 in 25 patients (34.7%) and T3-T4 in 47 patients (65.3%). At diagnosis, 16 (22.2%) patients had clinical and/or radiological nodal involvement and 7 patients (9.7%) distal metastasis. Among N0 patients, 13 (18%) experienced isolated lymph node recurrence. Two-year global survival was 60%; 5-year survival was 34%. The rate of lymph node invasion observed in squamous cell carcinoma of the hard palate and maxillary alveolar ridge does not differ from other oral cavity sites. Because nodal recurrence worsens the prognosis of such a patient, lymph node dissection should be considered at an early stage, even among N0 patients.

Results and Survival of Locally Advanced AJCC 7th Edition T4a Laryngeal Squamous Cell Carcinoma Treated with Primary Total Laryngectomy and Postoperative Radiotherapy.

PURPOSE: The objective of this study was to analyze the results and survival of patients with T4a laryngeal squamous cell carcinoma (SCC) treated, according to clinical practice guidelines, with total laryngectomy and postoperative radiotherapy (TL-PORT) in a large and homogeneous series. METHODS: Initial staging assessment, treatment details, pathologic features, follow-up, and patterns of recurrence were retrospectively reviewed in a large series of 100 patients treated in our center between 2001 and 2013 for T4a laryngeal SCC with TL-PORT. RESULTS: Two-, 5-, and 10-year overall survival rates were 65, 52.4, and 33.3 %, respectively, while 2-, 5-, and 10-year disease-free survival rates were 55, 42.6, and 31.8 %, respectively. In addition, 2-, 5-, and 10-year locoregional control rates were 77, 74, and 65.9 %, respectively. Central lymph node involvement was associated with pathologic subglottic extension (p = 0.01), lysis of the cricoid cartilage (p = 0.03), and tracheal extension (p = 0.02). Extracapsular spread of central lymph node metastases, the main prognostic factor identified by multivariate analysis, was associated with decreased locoregional control and survival rates. CONCLUSION: In this homogenously treated cohort, with consistent guideline application, surgery for T4a larynx cancer remains a standard of care, with current results used as a benchmark.

Sinonasal squamous cell carcinoma without clinical lymph node involvement : Which neck management is best?

OBJECTIVES: The purpose of this work was to report outcomes of patients with nonmetastatic sinonasal squamous cell carcinoma (SNSCC) and to discuss the impact of elective neck irradiation (ENI) and selective neck dissection (SND) in clinically negative lymph node (N0) patients. METHODS: Data from 104 nonmetastatic SNSCC patients treated with curative intent were retrospectively analysed. Uni- and multivariate analyses were used to assess prognostic factors of overall survival (OS) and locoregional control (LRC). RESULTS: Median follow-up was 4.5 years. Eighty-five percent of tumours were stage III-IV. Treatments included induction chemotherapy (52.9 %), surgery (72 %) and radiotherapy (RT; 87 %). The 5­year OS, progression-free survival, and LRC rates were 48, 44 and 57 %, respectively. Absence of surgery predicted a decrease of OS (hazard ratio [HR] 2.6; 95 % confidence interval [CI] 1.4-4.7), and LRC (HR 3.5; 95 % CI 1.8-6.8). Regional relapse was observed in 13/104 (13 %) patients and most common sites were level II (n = 12; 70.6 %), level III (n = 5; 29.4 %) and level Ib (n = 4; 23.5 %). Management of the neck in N0 patients (n = 87) included 11 % SND alone, 32 % ENI alone, 20 % SND + ENI and 37 % no neck treatment. In this population, a better LRC was found according to the management of the neck in favour of SND (94 % vs. 47 %; p = 0.002) but not ENI. CONCLUSION: SND may detect occult cervical positive nodes, allowing selective postoperative RT. ENI (ipsilateral level II, ±Ib and III or bilateral) needs to be proposed in selected patients, especially when SND has not been performed.

Influence of the vocal cord mobility in salvage surgery after radiotherapy for early-stage squamous cell carcinoma of the glottic larynx.

Disease relapses occur in up to 40% of cases after radiotherapy (RT) for early-stage glottic laryngeal neoplasms, and the foremost remaining treatment option is salvage total laryngectomy (STL). Our objectives were to review the outcomes of patients treated with salvage surgery after RT for early-stage carcinoma of the glottic larynx and to assess prognostic factors. We retrospectively analyzed 43 patients who underwent surgery. Overall and disease-free survival rates among subgroups were calculated and compared, stratified by preoperative stage, vocal cord mobility and postoperative histopathologic data. Recurrences occurred 22.7 months after the end of RT. Surgery was STL in 33 cases (76.8%). The main prognostic factors associated with survival rates were initial vocal cord mobility, vocal cord mobility at the diagnosis of recurrence, and changes in mobility. Vocal cord mobility is an important clinical criterion in treatment decision making for early-stage glottis carcinoma and remains important during follow-up.

Pyriform sinus squamous cell carcinoma: oncological outcomes in good responders of induction chemotherapy-based larynx preservation protocols.

Induction chemotherapy-based larynx preservation protocols use chemotherapy to select exclusively patients with 'chemosensitive' tumors for a nonsurgical treatment with radiation therapy. This study on pyriform sinus squamous cell carcinoma (SCC) is interested in the oncological outcome of treatment based on radiation therapy when offered to patients with tumors responding to induction chemotherapy. This was a retrospective cohort study. The cohort included good responders to induction chemotherapy, subsequently treated with definite radiation therapy (with or without concomitant chemotherapy) for pyriform sinus SCC, in a tertiary referral cancer center. The primary endpoints were overall, laryngectomy-free and disease-free survival and the secondary endpoints were analysis of treatment failures and possibilities of salvage treatment. Forty-two patients fulfilled the inclusion criteria and were retained for analysis; 7% were stage II (3/42), 48% stage III (20/42) and 45% stage IV (19/42). At 1, 3 and 5 years, the overall survival was 95% (40/42), 74% (31/42), and 60% (SE ≈ 0.08), respectively. For the same intervals, the laryngectomy-free survival was 90% (38/42), 69% (29/42) and 50% (SE ≈ 0.08), respectively. The estimated 5-year disease-free survival was also 50%. Disease-free survival was significantly better for N0 patients. There was a 28% recurrence rate, mainly in the primary tumor site (9/11), with or without simultaneous nodal recurrence. Interestingly, more than one-third of all oncologic failures occurred beyond the first 3 years of follow-up. Salvage treatment was not possible or definitely inefficient in at least 2/3 of all recurrences. In candidates for larynx preservation for a pyriform sinus SCC, good response to induction chemotherapy followed by definite radiation therapy seems to be associated with a more favorable prognosis. Nevertheless, in case of locoregional recurrence the possibilities for efficient salvage treatment are limited.

Concurrent use of cisplatin or cetuximab with definitive radiotherapy for locally advanced head and neck squamous cell carcinomas.

AIM: The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73%) with three cycles of cisplatin (100 mg/m(2), every 3 weeks) or BRT (n = 71; 27%) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005). RESULTS: Median follow-up was 29 months. In all, 56% of patients treated with CRT received the planned three cycles (92% at least two cycles) and 79% patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72% and 61%, respectively. In the multivariate analysis (MVA), T4 stage, N2-3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79%, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76% for CRT vs. 61% for BRT) and DC (2-year LRC: 81% for CRT vs. 68% for BRT) in comparison with BRT (p < 0.001 and p = 0.01 in the MVA). Subgroup analyses showed that T4 patients benefited significantly from CRT (vs. BRT) in LRC, while T1-3 did not. BRT patients had more G3-4 skin complications (p < 0.001) and CRT patients had higher rates of feeding tube placement (p = 0.006) and G3-4 gastrointestinal toxicities (p < 0.001). CONCLUSION: This retrospective analysis showed a better LRC in locally advanced HNSCC treated by cisplatin-based CRT than cetuximab-based BRT, and a nonsignificant trend towards an improved OS.