The incorporation of chemotherapy and radiation, either sequentially or concurrently, has been increasingly used for organ preservation in patients with advanced laryngeal cancer. Traditional outcome ...measures of clinical response such as locoregional control and survival have been similar for patients treated with chemoradiotherapy and those treated with total laryngectomy (TL). The impact of concurrent chemoradiotherapy for laryngeal preservation on the overall quality of life (QOL) of patients has not been clearly evaluated, particularly in direct comparison with TL.
To compare the QOL of patients treated with concurrent chemoradiotherapy with those treated with TL.
Nonrandomized, retrospective, cross-sectional study.
Academic tertiary care referral center.
The study included 42 patients with advanced stage III or IV cancer of the larynx, who were treated with either concurrent chemoradiotherapy or TL with postoperative radiation therapy. Patients had to be without evidence of recurrence and to have completed therapy at least 3 months prior to inclusion in the study. Quality of life was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) in tandem with the head and neck module (EORTC QLQ-H&N35).
On the core questionnaire (QLQ-C30), there were no statistically significant differences in the overall QOL score between the 2 groups. Functional subscale analysis revealed a trend for patients in the surgery and radiotherapy group to experience greater difficulties with social functioning (P =.18) relative to the chemoradiation group. On the QLQ-H&N35, surgery patients reported significantly greater difficulties with sensory disturbances (smell and taste, P =.001), use of painkillers (P =.049), and coughing (P =.004). On the other hand, chemoradiation patients reported significantly greater problems with dry mouth (P =.02).
Both chemoradiation and TL affect, albeit differently, the QOL of patients treated for advanced cancer of the larynx. Although these differences can be detected by functional and subscale analysis, the overall QOL scores of both groups seem similar.
Presentamos las metástasis durales como forma inusual de diseminación de tumores nasosinusales malignos tratados; se revisan 20 casos diagnosticados durante el seguimiento imagenológico a un grupo ...tratado con resección craneofacial anterior. Evaluamos metástasis durales en 12 carcinomas nasosinusales indiferenciados, 7 neuroblastomas olfatorios y un carcinoma adenoquístico. En neuroblastomas olfatorios aparecieron metástasis durales en promedio 7,3años postratamiento. La distancia máxima del tumor a la metástasis fue de 14cm para neuroblastoma olfatorio y de 4,3cm para carcinoma nasosinusal indiferenciado. Observamos metástasis durales en los agujeros de trepanación en el 50% de los carcinomas nasosinusales indiferenciados y en el 29% de los neuroblastomas olfatorios. Las metástasis durales presentaron patrón nodular (60%), multinodular (10%), quístico (15%) y en placa (15%). Proponemos un mecanismo venoso local de diseminación relacionado a disrupción tumoral o quirúrgica de la fosa craneal anterior. El seguimiento a largo plazo con inclusión craneal estaría indicado por la posible presentación tardía y distante de metástasis durales.
Dural metastases are an unusual form of spread in treated sinonasal malignancies. An analysis is presented of 20 cases of dural metastases diagnosed during imaging follow-up in a selection of cases in which anterior craniofacial resection was performed. They included 12 undifferentiated sinonasal carcinomas, 7 olfactory neuroblastomas, and 1 adenoid cystic carcinoma case. Dural metastases appeared on an average of 7.3years after treatment in olfactory neuroblastoma. The maximum distance from malignancy to dural metastases was 14cm for olfactory neuroblastoma, and 4.3cm for undifferentiated sinonasal carcinoma. Dural metastases in the Burr holes were observed in 50% of undifferentiated sinonasal carcinoma, and 29% of olfactory neuroblastomas. Dural metastases presented as a nodular (60%), multinodular (10%), cystic (15%), and plaque (15%) pattern. These are suggestive of a local venous spread mechanism related to tumour rupture during surgery of anterior cranial fossa. Long-term follow-up with cranial inclusion would be indicated, given the possible late and distant presentation of dural metastases.
Alkylating N-nitroso compounds can interact directly with DNA, forming O(6)-alkylguanine, a DNA adduct proved to be mutagenic and carcinogenic if not sufficiently repaired. A specific DNA repair ...enzyme, O(6)-methylguanine-DNA methyltransferase (MGMT), can remove the alkyl group from the O(6)-position of the guanine, thereby preventing its mutagenic and carcinogenic effects. Inactivation of the MGMT gene in association with promoter hypermethylation results in persistence of O(6)-alkylguanine in DNA, leading to G:C to A:T transition mutation and these G:C to A:T transition mutations can inactivate p53 tumor suppressor gene or activate ras proto-oncogene.
We analyzed MGMT promoter hypermethylation and protein expression patterns in 94 cases of primary head and neck squamous cell carcinoma (HNSCC) by methylation-specific PCR (MSP) and immunohistochemical staining. The results were then correlated with clinical follow-up data.
MGMT promoter hypermethylation was present in 17 of 94 patients (18.1%) and apparent loss of protein expression was seen in 19 of 93 HNSCC patients (20.4%). The presence of MGMT promoter hypermethylation was significantly correlated with loss of MGMT protein expression in HNSCC. Both MGMT promoter hypermethylation and loss of protein expression were significantly correlated to increased tumor recurrences and decreased patient survival, independent of other risk factors, such as tumor site, tumor size, nodal status, age, and chemoradiation therapy.
MGMT promoter hypermethylation and apparent loss of protein expression are reliable and independent prognostic factors in HNSCC. The above study may also provide guideline or basis for applying alkylating antitumor agents to patients with HNSCC that display MGMT promoter hypermethylation and/or loss of MGMT protein expression.
The hMLH1 gene is one of the mismatch DNA repair genes. Inactivation of the hMLH1 gene has been implicated in the tumorigenesis of many types of human cancers. In most sporadic forms of human ...cancers, promoter hypermethylation is responsible for hMLH1 gene inactivation. Lack of hMLH1 protein expression has been found in a subset of head and neck squamous cell carcinomas (HNSCCs). The purpose of this study was to investigate whether promoter hypermethylation causes hMLH1 gene inactivation in HNSCCs.
hMLH1 protein expression was determined by immunohistochemical staining in 62 cases, whereas hMLH1 gene promoter methylation was analyzed by methylation-sensitive restriction enzyme digestion, followed by polymerase chain reaction, in 35 cases of HNSCCs.
Sixteen (26%) of 62 cases of HNSCCs showed near-complete loss of hMLH1 protein expression on immunohistochemical staining. Twelve (92%) of 13 cases that were negative for the hMLH1 protein displayed promoter hypermethylation, whereas 17 (77%) of 22 cases positive for the protein were free of promoter methylation.
Promoter hypermethylation may be an important mechanism for hMLH1 gene inactivation in a subset of HNSCCs.
Head and neck squamous cell carcinoma (HNSCC) is a multistage process during which adverse genetic alterations accumulate resulting in loss of cell cycle control, selective cell overgrowth, and ...ultimately formation of malignancy. Among various genetic alterations in HNSCC is increased microsatellite instability (MSI). hMLH1 is one of the major mismatch DNA repair genes, the inactivation of which caused increased MSI in a variety of human cancers including HNSCC. While somatic mutation is a major mechanism of the hMLH1 gene inactivation in hereditary form of human cancer, promoter hypermethylation appears to be primarily involved in the inactivation of the hMLH1 gene in sporadic form of human cancers. In the current study, we analyzed 78 cases of HNSCC for hMLH1 protein expression and promoter hypermethylation by IHC and methylation-specific PCR (MSP). Twenty-four of 78 cases (31%) of HNSCC contained markedly reduced levels of the hMLH1 protein. Based on the IHC results, 8 cases without and 8 with hMLH1 protein expression (total of 16) were further analyzed by MSP. Seven of 8 cases (88%) that were negative for the hMLH1 protein displayed promoter hypermethylation, whereas 7 of 7 cases (100%) strongly positive for the protein were free of promoter methylation. This study confirms our previous conclusion that promoter hypermethylation represents a major mechanism of the hMLH1 gene inactivation in HNSCC.
To evaluate the efficacy and toxic effects of intensive chemoradiotherapy as a primary modality for organ preservation in patients with advanced squamous cell carcinoma of the head and neck (SCCHN) ...and to define the patterns of treatment failure associated with this therapy.
Retrospective review.
Tertiary care referral center.
A total of 127 consecutive patients with advanced SCCHN treated with primary concurrent chemoradiotherapy.
Efficacy data included the rates of tumor response to therapy, organ preservation, disease recurrence, overall and disease-specific survival, and patterns of treatment failure. Toxic effect data included the rate and grade of treatment-related complications and the rate of unscheduled hospital admissions for managing treatment-related toxic effects.
Ninety-six patients (76%) were men and 31 (24%) were women. Average age at diagnosis was 62 years (range, 37-85 years). The primary tumor site was the oropharynx in 58 patients (46%), the larynx in 36 (28%), the hypopharynx in 20 (16%), the oral cavity in 10 (8%), and another site in 3 (2%). Most patients (91%) had stage III or IV disease. Average follow-up was 36 months. Primary chemoradiotherapy achieved complete response at the primary tumor site in 109 patients (86%). Patients with partial response, stable or progressive disease, or recurrence at the primary site underwent salvage surgery. Overall, at mean follow-up of 3 years, local disease control was achieved in 113 patients (89%), and organ preservation was possible in 102 patients (80%). Two thirds of all patients (n = 83) had clinical N+ disease. Complete clinical response to chemoradiotherapy in the neck was achieved in 57 of these patients (69%). However, complete response to chemoradiotherapy was 93%, 62%, and 47% for N1, N2, and N3 disease, respectively (P <.001). Patients achieving less than complete clinical response underwent salvage neck dissection. Overall, at an average follow-up of 36 months, regional disease control was achieved in 76 (92%) of the 83 patients with neck metastasis. Despite this high locoregional control rate, distant metastasis occurred in 18 patients (14%), was the most common site of disease recurrence (53%), and accounted for almost 40% of all treatment failures. Severe (grade 3 or 4) mucositis and neutropenia occurred in 33% and 25% of patients, respectively. Two patients (2%) died of treatment-related toxic effects. At 3-year mean follow-up, disease-specific and overall survival were 72% and 57%, respectively. Most deaths were due to distant metastasis, comorbidity, and second primary tumors.
High rates of locoregional disease control and organ preservation are achievable with primary chemoradiotherapy in patients with advanced SCCHN, but they are associated with severe treatment-related toxic effects. Despite this effective local and regional disease control, improved survival is hampered by the relatively high incidence of distant metastasis, second primary tumors, and comorbidity.
Subglottic cancer Hanna, E Y
American journal of otolaryngology,
09/1994, Volume:
15, Issue:
5
Journal Article
Peer reviewed
In summary, subglottic tumors are fortunately uncommon. They tend to present late with extensive disease, and are difficult to assess clinically. CT and MRI can be helpful in this regard. They have a ...tendency for extra laryngeal spread and paratracheal lymph node metastases. Aggressive surgical therapy is therefore recommended. This usually includes a wide field laryngectomy, an adequate low tracheal margin, and bilateral paratracheal lymph node dissection. The thyroid gland should be removed on the ipsilateral side, and if there is evidence of gross invasion of the thyroid gland, total thyroidectomy should be performed. Postoperative radiation therapy is recommended to both sides of the neck, stoma, and upper mediastinum. This will hopefully reduce the risk of stomal recurrence.
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