The Role of Audiometry prior to High-Dose Cisplatin in Patients with Head and Neck Cancer.

OBJECTIVES: To analyze the role of audiometry in considering change to a less ototoxic treatment in head and neck cancer (HNC) patients. METHODS: Consecutive patients prescribed high-dose cisplatin (100 mg/m2) between January 2013 and February 2015 were enrolled. Audiometry was performed at baseline and before cisplatin. Change to a less ototoxic agent or reduced cisplatin dose was considered with audiometric decreases >25 dB. RESULTS: A total of 103 patients were included; the median age of the patients was 59 years (range 18-75). Cisplatin was intended curative (58%), adjuvant (32%), or palliative (10%). Forty-two participants (41%) did not commence high-dose cisplatin because of baseline audiometric alterations. Of 61 patients treated with high-dose cisplatin, 40 (66%) showed marked ototoxicity at the end of treatment. The mean hearing loss between initial and final audiometries showed a hearing loss at 4 and 8 kHz in both ears (p = 0.002). Thirteen patients switched to carboplatin and 15 to a lower dose of cisplatin. The outcome was not significantly altered when cisplatin was replaced with carboplatin or cetuximab. CONCLUSIONS: Audiometric alterations are common in HNC with high-dose cisplatin, and switching to a less ototoxic regimen does not adversely affect outcome. Audiometric examination could help to prevent hearing loss in this population.

[The role of chemotherapy in advanced oral cavity cancer]. / El papel de la quimioterapia en el cáncer de la cavidad oral avanzado.

OBJECTIVE: To evaluate the role of chemotherapy in advanced cancer of the oral cavity by assessing its influence on the survival of patients receiving palliative care and its ability to improve the expectations of curative surgery. PATIENTS AND METHOD: Ninety-nine consecutive patients were analyzed to assess their course, the prognostic factors for tumour progression, and overall survival after treatment with two different chemotherapy regimes: cisplatin plus bleomycin (n=45) or cisplatin plus 5-fluorouracil (n=52). For the analysis, patients were split into groups depending on the treatment intention: palliative (n=41) or neo-adjuvant (n=56). RESULTS: The response rate was 56.7%. The response was greater in the neo-adjuvant group (73.2%) than among the palliative patients (36.6%) (P<0.001); greater with the bleomycin regime (73.3%) than with 5-fluorouracil (44.2%) (P=0.003); and greater in patients with stage III (77.8%) than stage IV (50%) (P=0.021). Survival was higher among patients receiving bleomycin than in those on 5-fluorouracil (P=0.019) and among those with stage III than stage IV (P=0.013). In the palliative treatment group, the response was associated with greater survival (P<0.001). In the neo-adjuvant group, 30 patients (53.6%) underwent surgery, with complete resection in 26 of them (86.7%). Sixteen cases (61.5%) presented recurrence. Chemotherapy response was not associated with operability. Survival was higher in the group with complete tumour resection (P<0.041). CONCLUSIONS: The response to chemotherapy in oral cavity tumours was greater in patients with stage III and in those receiving bleomycin. Chemotherapy may improve survival in palliative cases. In neo-adjuvant cases, no great influence was seen in the conversion of doubtful cases into candidates for surgery.

Predictors of tonsillar tissue HIV-1 viral burden at baseline and after 1 year of antiretroviral therapy.

In 81 antiretroviral-navie HIV-1 chronic-infected patients, we found a correlation among tonsillar tissue viral load, and virological and immunological measures in blood at baseline. No correlation was observed after 1 year of antiretroviral therapy. A protease inhibitor-containing regimen was the best predictor of good tonsillar tissue virological response.

Treatment of 125 sinonasal tumors: prognostic factors, outcome, and follow-up.

We reviewed our experience with sinonasal cancer patients to assess the prognostic factors. Between 1974 and 1995, we enrolled 125 patients (58 + 16 years [mean age + SD]; 94 males and 31 females). Tumor stage distribution was: T1, 64 patients; T2, 36 patients; and T3, 25 patients. Surgery as a primary treatment was selected for 106 patients (55 cases of surgery alone, 40 cases of surgery plus radiotherapy, and 11 cases of surgery plus chemotherapy with/without radiotherapy). The 1-, 5-, and 10-year overall survival was 75.0%, 37.2%, and 24.7%, respectively. The parameters with statistical prognostic significance were nodal stage, locoregional failure, and tumor stage. Histological type and primary site had no prognostic value. There were no significant survival differences between surgery alone and surgery plus radiotherapy. Sinonasal tumors have a poor survival, despite early diagnosis, radical surgical resection, and strict follow-up. Radiotherapy seems not to be clearly necessary in stage T1.

Transoral laser surgery for hypopharyngeal carcinomas.

PURPOSE OF REVIEW: Organ preservation strategies are a major focus of interest in head and neck cancer. There are two ways to preserve the function in the treatment of squamous cell carcinomas of the hypopharynx: organ-sparing surgery or neoadjuvant or concomitant chemoradiotherapy. From the surgical point of view, the possibilities of organ sparing have been increased with the use of transoral carbon dioxide laser surgery. Our purpose is to review this technique as a preservation surgical strategy for hypopharyngeal carcinomas. RECENT FINDINGS: The role of primary surgery in the initial treatment of head and neck carcinomas is being reviewed. The transoral laser resection of hypopharyngeal carcinomas is the least established of the transoral laser surgical approaches. Recent data suggest that selected hypopharyngeal tumors may be treated with transoral laser surgery, achieving very good oncologic and functional outcomes. SUMMARY: Transoral carbon dioxide laser surgery is an alternative to treat hypopharyngeal carcinomas. Early tumors may be removed by a transoral approach with high local control rates and function preservation in most of the patients. For more advanced tumors experience is still limited, and the role of this technique has not yet been defined.

Human papillomaviruses are identified in a subgroup of sinonasal squamous cell carcinomas with favorable outcome.

BACKGROUND: The role of human papillomavirus (HPV) in the pathogenesis of squamous cell carcinomas (SCCs) of the sinonasal tract and its clinicopathological implications were evaluated. METHODS: All SCCs of the sinonasal tract diagnosed in the Hospital Clinic of Barcelona from 1981 to 2006 were retrospectively evaluated (N = 60). Clinical and pathological data were reviewed. HPV infection was determined and typed by amplification of HPV DNA by polymerase chain reaction using the SPF-10 primers. p16(INK4a) expression was determined by immunohistochemistry. Overall and progression-free survival for HPV-positive and -negative patients was estimated by Kaplan-Meier analysis and by the use of a multivariate Cox proportional hazards model. RESULTS: HPV DNA was detected in tumor tissue of 12 of 60 (20%) patients. HPV16 was identified in 11 tumors and HPV35 in 1. Immunohistochemistry for p16(INK4a) stained all HPV-positive and no HPV-negative tumors (P < .001). No differences were observed in terms of site and histological grade or stage at presentation between HPV-positive and -negative tumors. However, HPV-positive patients had a significantly better 5-year progression-free survival (62%; 95% confidence interval [CI], 23%-86% vs 20%; 95% CI, 9%-34%; P = .0043, log-rank test) and overall survival (80%; 95% CI, 20%-96% vs 31%; 95% CI, 15%-47%; P = .036, log-rank test) than patients with HPV-negative tumors. In multivariate analysis, HPV-positive tumors were associated with improved progression-free survival (hazard ratio, 0.21; 95% CI, 0.17-0.98; P = .012). CONCLUSIONS: A subgroup of sinonasal SCCs is associated with HPV infection. These tumors have a significantly better prognosis.

Prognostic significance of surgical margins in transoral CO2 laser microsurgery for T1-T4 pharyngo-laryngeal cancers.

Histological affected or close margin is an adverse factor in conventional surgery of larynx-hypopharynx cancer. Our objective was to analyze the relevance of the margins in transoral laser microsurgery (TLM). A retrospective study of 357 consecutive patients with cancer of the larynx and hypopharynx (T1-T4) treated with TLM. Three possible margins were considered: tumor free, affected, and uncertain. An affected margin showed marked tumor infiltration. An uncertain margin was defined when the sample was insufficient, when it showed carbonization impeding accurate evaluation, or when tumor cells were less than 2 mm. Margins were free in 254 (71.1%) patients, affected in 64 (17.9%) and uncertain in 39 (10.9%). One hundred and three patients (28.9%) presented tumor relapse. The margins were associated with tumor relapse (P < 0.001), but were not significantly related to the tumor site (P = 0.307), the pT classification (P = 0.183), or the difficulty of surgical exposure (P = 0.427). Distant metastases were found in 4.7% of the patients with free margins, in 7.7% of those with uncertain margins, and in 14.1% with affected margins. These differences were statistically significant (P = 0.028). Tumor involvement of the surgical margin was associated with higher rates of local relapse, distant metastasis and the necessity of salvage surgery, together with a lower specific actuarial survival rate.

Immunoarchitecture of lymphoid tissue in HIV-infection during antiretroviral therapy correlates with viral persistence.

Plasma viral load and T-cell subset determinations in blood are the markers used for monitoring HIV-1 infection. However, key pathogenesis events, viral replication and most immunologic changes occur in the lymphoid tissues. We have studied the tonsillar biopsies of 30 patients in the early stages of the disease, before initiating treatment and after 12 and 36 months of fully effective highly active antiretroviral therapy. We have investigated the HIV RNA by polymerase chain reaction (lymphoid tissue viral load), the immunohistochemical HIV-p24 antigen expression, as well as the lymphoid tissue architecture and lymphoid cell subsets using morphometry. The lymphoid tissue viral load and the immunoexpression of p24, which was found to be mainly associated with follicular dendritic cells, decreased significantly after treatment, but did not disappear in all cases, even after 36 months of treatment. A significant improvement of the lymphoid tissue architecture was also observed after treatment, with recovery of follicular structures. These histological changes correlated with the lymphoid tissue viral load. Moreover, the counts of CD4+ increased whereas CD8+ and cytotoxic lymphocytes (CD8+ granzyme B+) decreased significantly, the latter in both interfollicular and intrafollicular areas. However, these cellular counts after treatment did not reach those of lymphoid tissue of non-HIV-infected patients used as control cases. Naive (CD45RA+) and memory (CD45RO+) cells also improved significantly after treatment. In conclusion, in HIV-infection the impact of treatment can only be assessed completely in the lymphoid tissue reservoir, where most of the virus is stored and associated with follicular dendritic cells. Highly active antiretroviral therapy produces a significant recovery of lymphoid tissue architecture and lymphoid cell subsets, which are associated with the decrease of lymphoid tissue viral load. However, these parameters studied in lymphoid tissue are not re-established completely, even after 36 months of highly active antiretroviral therapy.

Multidisciplinary approach in advanced cancer of the oral cavity: outcome with neoadjuvant chemotherapy according to intention-to-treat local therapy. A phase II study.

OBJECTIVES: To determine outcomes in local-regional control and overall survival in patients with squamous locally advanced cancer of the oral cavity, based on intention-to-treat with neoadjuvant chemotherapy followed by surgery or radiation therapy. METHODS: Two hundred and four out of 1,089 patients analyzed met the defined criteria. All had squamous cell carcinomas of the oral cavity in stage III or in nonmetastatic stage IV and were selected for surgery or radiation therapy (if located in the tonsils or in the base of the tongue). Chemotherapy was based on cisplatin 120 mg/m(2) i.v. day 1 plus bleomycin 20 mg/m(2) days 1-5 in continuous i.v. perfusion or plus 5-fluorouracil 1,000 mg/m(2) days 1-5 in continuous i.v. perfusion. A total of 418 cycles were given to 204 patients (mean 2.049 per patient). Definitive surgery (n = 73; plus adjuvant radiation therapy) or definitive radiation therapy (n = 131) was performed. RESULTS: One hundred thirty-five out of 204 (66%) patients were chemotherapy responders, 16% complete and 50% partial. One hundred ninety-four patients (95%) completed 2 courses of chemotherapy. After neoadjuvant chemotherapy, 34 out of 46 patients considered inoperable initially (74%) obtained a disease-free status with surgery. Eighty-three percent of surgical patients obtained a disease-free status (initial tumor control) versus 72% of radiation therapy patients. Disease-free survival rates at 5 years were 26 and 22%, respectively. A better prognosis was observed in stage III over IV (p = 0.02); primary tumor in the retromolar trigone, palate or buccal mucosa over tongue, tonsil or floor of the mouth (p = 0.0085); negative cervical nodes over positive (p = 0.0186); responders to chemotherapy over nonresponders (p = 0.0003); and adjuvant postsurgical radiation therapy (p = 0.0013). Causes of death were relapses in local area (86%), regional nodes (10.5%) or distant metastases (3.5%). Eleven patients (5%) died of a second primary. The main toxic effects were vomiting in 9% of patients and hemolytic-uremic syndrome in 3% of the patients treated with bleomycin. CONCLUSIONS: In locally advanced squamous cell carcinoma of the oral cavity, neoadjuvant chemotherapy induces a high response rate that may facilitate definitive surgery or radiotherapy. In this study, patients have an acceptable long-term survival.