Photodynamic therapy of early stage oral cavity and oropharynx neoplasms: an outcome analysis of 170 patients.

The indications of photodynamic therapy (PDT) of oral cavity and oropharynx neoplasms are not well defined. The main reason is that the success rates are not well established. The current paper analyzes our institutional experience of early stage oral cavity and oropharynx neoplasms (Tis-T2) to identify the success rates for each subgroup according to T stage, primary or non-primary treatment and subsites. In total, 170 patients with 226 lesions are treated with PDT. From these lesions, 95 are primary neoplasms, 131 were non-primaries (recurrences and multiple primaries). The overall response rate is 90.7% with a complete response rate of 70.8%. Subgroup analysis identified oral tongue, floor of mouth sites with more favorable outcome. PDT has more favorable results with certain subsites and with previously untreated lesions. However, PDT can find its place for treating lesions in previously treated areas with acceptable results.

Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma.

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO's MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC.

The value of computed tomography scan versus an explorative surgical approach for removal of squamous cell carcinoma of the posterior pharyngeal wall.

BACKGROUND: The prevertebral fascia plays a key role in surgery of posterior pharyngeal wall tumors. Invasion of the prevertebral muscles determines the irresectability of the tumor and accurate diagnosis of invasion posteriorly is a prerequisite for major ablative surgery. METHODS: A retrospective study was performed to define the value of CT scanning versus open neck exploration with regard to the resectability of posterior pharyngeal wall carcinoma. The predictive value of preoperative CT scans was assessed and compared with the outcome of open neck exploration and resectability of the primary tumor, using the final histopathology report as a gold standard. RESULTS: Nineteen patients with 20 tumors were included in this study. Overall the CT scan was correct concerning prevertebral muscle status in 4 out of 20 (20%), whereas open neck exploration was correct in 18 tumors (90%). CONCLUSION: The predictive value of a suspicious CT scan in determining prevertebral muscle invasion is extremely low in this study. Open neck exploration seems to be superior for determining resectability of posterior wall carcinoma.

A new problem-solving indwelling voice prosthesis, eliminating the need for frequent Candida- and "underpressure"-related replacements: Provox ActiValve.

OBJECTIVES: To develop and clinically assess a new prosthesis for voice rehabilitation after total laryngectomy that solves the problem of frequent Candida- and "underpressure"-related replacements. MATERIAL AND METHODS: We designed a voice prosthesis with a new valve mechanism, applying Candida-resistant fluoroplastic (Teflon-like) material for the valve and valve seat and magnets to generate an active closing force, preventing inadvertent opening of the valve during swallowing or deep inhalation. Several prototypes were tested in 13 laryngectomized patients and, subsequently, the final design was assessed in a prospective clinical trial in a cohort of 18 patients with a short device lifetime of their standard indwelling voice prosthesis (mean 30 days). RESULTS: Prototype testing and the long-term clinical trial confirmed that the new valve material remained free of Candida growth and that the use of magnets can prevent inadvertent opening of the valve during swallowing and/or deep inhalation. This resulted in a highly significant increase in device lifetime in the 18 laryngectomized patients in the prospective trial (14-fold increase on average, range 3-39-fold; p < 0.001). Lubrication with special medical-grade fluoridated silicone oil is favorable in patients who experience possible adhesion of the valve to the valve seat. CONCLUSIONS: This new voice prosthesis, the Provox ActiValve, represents a solution for patients who have the problem of requiring very frequent voice prosthesis replacements due to excessive Candida growth and/or inadvertent opening of the valve by swallowing and inhalation-related underpressure in the esophagus.

Lower mortality from nasopharyngeal cancer in The Netherlands since 1970 with differential incidence trends in histopathology.

OBJECTIVE: Nasopharyngeal carcinoma (NPC) is rare in western countries albeit affected by common and unrelated phenomena: smoking less in men, more in women and immigration from China and North Africa. We studied trends in NPC incidence, tumour morphology, survival and mortality in order to assess progress against this cancer. MATERIALS AND METHODS: A trend analysis was performed with nationwide incidence and survival data (from The Netherlands Cancer registry in 1989-2009), followed by analysis of mortality (data from Statistics Netherlands) covering the period 1970-2009, and calculating estimated percentages of change (EAPC) in both. According to the WHO classification we distinguished keratinizing SCC (WHO-I), differentiated (WHO-IIA) and undifferentiated (WHO-IIB) non-keratinizing carcinoma. RESULTS: NPC incidence significantly decreased since 1989, especially in males (EAPC 1989-2009: -1.3; 95% CI: -2.5, -0.2) and in patients with keratinizing SCC (WHO-I) (EAPC: -3.6; 95% CI: -5.3, -1.8). By contrast, the incidence of differentiated non-keratinizing tumours (WHO-IIA) significantly increased in the same period (EAPC: 9.6; 95% CI: 5.6, 13.5). One- and three-year relative survival, as an indicator of disease-specific survival increased slightly from 79% to 81% and from 57% to 65% since 1989. NPC mortality significantly decreased since 1970 (EAPC: -1.2; 95% CI: -1.8, -0.5) and more pronounced since 1989 (EAPC: -3.0; 95% CI: -4.3, -1.6). CONCLUSION: During the past two decades, the incidence of NPC in The Netherlands decreased mainly by less keratinizing, supposedly smoking-related NPC (WHO-I). However, the incidence of non-keratinizing NPC (WHO-IIA, B) increased, most likely due to EBV infection and thus related to higher immigration levels of people from high-incidence areas.