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.
Full-dose reirradiation combined with chemotherapy has been shown to be feasible after salvage surgery with acceptable toxicity. The Groupe d'Etude des Tumeurs de la Tête et du Cou and Groupe ...d'Oncologie Radiothérapie Tête Et Cou groups performed a randomized study to assess its efficacy.
Between 1999 and 2005, 130 patients with head and neck cancer were treated with salvage surgery and randomly assigned to full-dose reirradiation combined with chemotherapy (RT arm) or to observation (a "wait and see" approach; WS arm). Eligibility criteria were recurrence or a second primary tumor in a previously irradiated area, no major sequelae resulting from the first radiotherapy, good general condition, no distant metastasis, and salvage surgery with macroscopic complete resection. Patients in the RT arm received 60 Gy over 11 weeks combined with concomitant fluorouracil and hydroxyurea.
Sixty-five patients were randomly assigned to each arm. There was no imbalance in the distribution of the main tumor and patients characteristics. The most serious acute toxicity in the RT arm was mucositis, attaining grade 3 or 4 in 28% of patients. At 2 years, 39% of patients in the RT arm and 10% in the WS arm experienced grade 3 or 4 late toxicity according to Radiation Therapy Oncology Group criteria (P = .06). Disease-free survival (DFS) was significantly improved in the RT arm, with a hazard ratio of 1.68 (95% CI, 1.13 to 2.50; P = .01), but overall survival (OS) was not statistically different.
Full-dose reirradiation combined with chemotherapy after salvage surgery significantly improved DFS, but had no significant impact on OS. An increase in both acute and late toxicity was observed.
Background
Parotid spread tumor may occasion wide defect with facial nerve sacrifice. We report our one time reconstruction experience of this defect using a thoracodorsal artery perforator and nerve ...flap (TAPN).
Methods
Eight patients underwent a radical parotidectomy with facial nerve sacrifice between February 2010 and June 2016. A single time reconstruction was performed using a thoracodorsal artery perforator and nerve flap, with skin or fat paddle. The thoracodorsal nerve vascularized was harvested and used to reconstruct the facial nerve from the trunk to four until six distal branches. Patients underwent physiotherapy for 3 months at least. Facial outcomes were assessed using House‐Brackmann scale and eFACE application.
Outcomes
Mean follow‐up was 30 months. No complication occurred on donor site. All patients recovered a complete soft eye closure. No Frey syndrome occurred.
Conclusion
TAPN is adapted to wide and complex parotid defects.
Objectives/Hypothesis
To compare voice handicap and quality of life after radiotherapy (RT) versus transoral laser surgery (LS) for T1a glottic carcinoma.
Study Design
Retrospective study (1996–2011) ...of patients treated with RT or LS for T1a glottic squamous cell carcinoma with curative intent.
Methods
Disease‐free patients were assessed using Voice Handicap Index (VHI 30) and European Organization for Research and Treatment of Cancer Head and Neck Quality of Life (EORTC QLQ‐HN35) questionnaires.
Results
Of 147 patients, 95 (65%) completed the questionnaires: fifty‐one patients an average of 8 years after RT and 44 patients an average of 4 years after LS (no difference in age or sex ratio). The average total VHI 30 was 13.1 for RT and 29.2 for LS (P < .0001), with average emotional, physical and functional subscores significantly different. The average total EORTC QLQ‐HN35 was 37.7 for RT versus 40.7 for LS (P = .7), with a difference only in the speaking subscore (P = .04).
Conclusions
Long‐term subjective voice‐related quality of life was worse after LS, with no difference in other domains. These results should be interpreted in light of the biases inherent in retrospective studies.
Level of Evidence
4. Laryngoscope, 124:1398–1401, 2014
Objectives/Hypothesis:
To evaluate the reliability of the sentinel node (SN) biopsy in early oral squamous cell carcinomas.
Study Design:
Prospective cohort study.
Methods:
We conducted a primary ...prospective study on 53 consecutive patients presenting T1, T2 N0 squamous cell carcinomas of the oral cavity between January 2000 and June 2003. Primary results demonstrated a negative predictive value of 100%. The series was then extended until June 2010, with a total number of 166 successful procedures.
Results:
The cohort accounted for 118 males and 48 females with a mean age of 56 years. The median follow‐up period was 36 months. There were 42 patients (25%) with positive SNs, 14 of them (33%) only harboring micrometastasis. The negative predictive value of the sentinel node biopsy was 95.2%. The SN involvement was strongly correlated with the tumor location (34% of SN+ for the tongue vs. 13% for the floor of mouth, P = .003), tumor stage (18% of SN+ for T1 vs. 40% for T2, P = .002), depth of invasion (median depth for SN+ lesions was 6.5 mm vs. 4 mm for SN− lesions, P = .028), and lymphovascular involvement (P = .002). The false‐negative rate of frozen section examination was 42%.
Conclusions:
The sentinel node biopsy appears to be an excellent staging method in early oral cancers. This study also provides evidence that routinely undiagnosed micrometastasis may have clinical significance.
To investigate the prognostic value of tumor infiltrating lymphocytes (TILs: CD8+ and FoxP3+), and PD-L1 expression in patients with head and neck squamous cell carcinoma (HNSCC) treated with ...radiotherapy combined with cisplatin (CRT) or cetuximab (BRT). Immunohistochemistry for CD8, FoxP3 was performed on pretreatment tissue samples of 77 HNSCC patients. PD-L1 results were evaluable in 38 patients. Cox regression analysis was used to analyze the correlations of these biomarkers expression with clinicopathological characteristics and treatment outcomes. High CD8+ TILs level was identified in multivariate analysis (MVA) as an independent prognostic factor for improved progression-free survival with a non-significant trend for better overall survival (OS). High FoxP3+ TILs and PD-L1+ correlated with a favorable OS in the uni-variate analysis, respectively, but not in the MVA. In subgroup analysis, CD8+TILs appear to play a pivotal role, p16+/high CD8+TILs patients had superior 5-year OS compared with p16+/low CD8+TILs, p16-/ high CD8+TILs, and p16-/ low CD8+TILs patients. p16+/PD-L1+ patients had improved 3-year OS compared with p16+/PD-L1-, p16-/ PD-L1+, and p16-/ PD-L1- patients. In low CD8+ TILs tumors, 5-year loco-regional control of patients treated with CRT was improved vs. those with BRT (p = 0.01) while no significant difference in high CD8+ TILs was observed. CD8+ TILs correlated with an improved clinical outcome in HNSCC patients independent of Human papillomavirus status. The immunobiomarkers may provide information for selecting suitable patients for cisplatin or cetuximab treatment. Additionally, the impact of TILs and PD-L1 of deciphering among the p16+ population a very favorable outcome population could be of interest for patients tailored approaches.
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