Late local recurrence after radiotherapy for tongue and early glottic carcinoma

BACKGROUND/AIM: Late local recurrence after radiotherapy for tongue and early glottic carcinoma is rarely discussed. In the head and neck cancer, approximately 90% of local recurrence occurred within 2 years after radiotherapy. However, we found that late local recurrence after radiotherapy for glottic cancer was not rare. Our aim was to evaluate the late local recurrence after radiotherapy for early glottic and tongue cancer. PATIENTS AND METHODS: From 1967 through 1982, 633 patients with tongue carcinoma and 330 patients with early (T1T2N0) glottic carcinomas were treated at the Department of Radiology, Osaka University Hospital. Of these 821 patients, 329 patients with tongue carcinoma and 221 patients with early glottic carcinoma survived at 5 years after radiotherapy without local recurrence. For tongue carcinoma, patients were divided by T category. For early glottic carcinoma, patients were divided by the tumor response at 40 Gy. RESULTS: Late local recurrence occurred in 23 of 329 patients (7%) with tongue carcinoma, and in 9 of 221 (4%) with early glottic carcinoma. For tongue carcinoma, late recurrence occurred in 19 of 249 patients (8%) in stage I and II, and 4 of 80 patients (5%) in stage III and IV. For glottic carcinoma, late recurrence occurred in 8 of 137 patients (6%) with tumor clearance at 40 Gy and 1 of 63 patients (2%) with tumor persistence at 40 Gy. The incidence of double cancer was also evaluated. Of 329 5-year survivors with tongue carcinoma, 39 patients (12%) had another malignancy, and 26 patients of 221 5-year survivors with early glottic carcinoma (12%) had also another malignancy. Of 39 double primaries of tongue carcinoma, 10 patients (26%) had head and neck malignancies, and none of 26 double primaries of early glottic carcinoma. CONCLUSION: Late local recurrence was not rare in tongue and early glottic cancer. Poor prognostic group showed lower incidence of late recurrence than good prognostic group. This result suggests that secondary tumor at the same site of primary tumor is late local recurrence.     

P53 overexpression in head and neck carcinoma and radiotherapy results

PURPOSE: P53 gene mutations are the common genetic changes encountered in human cancers, and there is extensive evidence that the P53 status may determine tumor response to therapy. This study was carried out to investigate whether there is any correlation between accumulation (overexpression) of P53 protein and poor prognosis in patients with head and neck carcinomas treated with radical radiotherapy. METHODS AND MATERIALS: Seventy-nine patients with head and neck carcinomas who were diagnosed and treated in 1989-90 with curative radiotherapy were studied retrospectively. Paraffin sections from archival material were studied using immunohistochemical staining (IHC) with mouse monoclonal antibodies (D0-7) to human P53 protein. Univariate and multivariate analysis of loco-regional tumor control and patient survival were performed on possible prognostic factors. RESULTS: Forty-two (53%) patients showed positive IHC staining in their tumors. Fifty-three percent of the laryngeal, 64% of the oropharyngeal, and 43% of the oral cavity carcinomas showed P53 overexpression. All tumor specimens with vascular, lymphatic, and/or sarcolemmal invasion showed P53 overexpression. The proportion of tumor-stained nuclei was higher in the poorly differentiated than in the well and moderately differentiated tumors (p < 0.05), but there was no correlation with the patient overall or disease-free 5-year actuarial survival. There was no difference in the 5-year actuarial survival and disease-free survival between patients with P53 immunostaining in their tumors and those with no immunostaining (59% vs. 65% and 57% vs. 51%, respectively). The TNM tumor stage was the most significant prognostic factor with 5-year actuarial survival of 87% for early and 14% for late stages (p < 0.0001). There was a significant correlation between immunostaining and history of smoking (p = 0.02). CONCLUSION: The data demonstrate that the P53 accumulation as detected by immunohistochemical staining in a group of head and neck carcinomas was not predictive of patient's poor survival or disease-free survival. Multivariate statistical analysis showed that the TNM tumor stage was the only significant prognostic factor. There was a significant association between P53 accumulation and smoking.     

Significance of DNA ploidy in the treatment of T1 glottic carcinoma

OBJECTIVE: To assess the role of DNA ploidy as a predictor of radioresistance in T1 glottic carcinoma. DESIGN: Case-control study. Flow cytometric DNA ploidy measurements were performed on formalin-fixed paraffin-embedded tumor specimens from 15 patients with T1 glottic laryngeal carcinomas in whom radiotherapy had failed and from a matched group of 15 patients in whom an identical radiotherapy regimen was curative. Analysis of DNA content was performed blind to outcome of treatment. SETTING: Academic tertiary referral medical center. PARTICIPANTS: Thirty patients with clinically staged T1, N0, M0 glottic carcinoma. INTERVENTION: All patients received radiation to the larynx through opposed lateral ports at a total dose of 64 to 70 Gy. RESULTS: Ten diploid and five aneuploid histograms were found in the resistant group, and six diploid and nine aneuploid histograms were found in the radiosensitive group. This difference was not statistically significant. A trend toward a higher relapse rate after radiotherapy (62.5%) among patients with diploid tumor compared with those with aneuploid tumor (35.7%) was noted. CONCLUSIONS: DNA ploidy did not predict response to radiotherapy in patients with T1 glottic cancer, probably because of the small number of patients. A trend toward lower risk of local recurrence after radiotherapy in aneuploid tumors was noted. A larger prospective study is needed to assess the value of DNA ploidy in the treatment of early laryngeal cancer.     

Management for stage II glottic carcinoma: radiation therapy or surgery

AIM: To analyze the results of stage II glottic carcinoma treated with radiotherapy or surgery. PATIENTS AND METHOD: One hundred thirty-four patients with squamous cell carcinoma of the T2N0M0 glottic carcinoma treated at the Osaka Medical Center for Cancer and Cardiovascular Diseases from 1979 through 1991 were reviewed. The 5-year disease-free survival and laryngeal preservation rate and prognostic factors were examined. Treatment was radiation therapy with salvage surgery for failure or surgery alone. RESULTS: The 5-year disease-specific survival rate for the radiotherapy group was 100% and for the surgery group, 93% (p = 0.055). In the surgery group 5-year disease-specific survival rate for the subgroup of cord mobility was 94% and that of impaired cord mobility, 89% (p = 0.5354). Concerning laryngeal preservation the radiotherapy group showed better preservation rate than the surgery group in the subgroup of cord mobility, i.e., 41/51 (80%) versus 6/55 (11%) (p < 0.001) although significant difference was not observed in the lesion with impaired cord mobility, 2/5 versus 4/22 (p = 0.171). CONCLUSION: We recommend radiation therapy for stage II glottic carcinoma with normal cord mobility, although further study is needed to improve the preservation rate of the larynx with keeping the disease-specific survival for the lesion with impaired cord mobility.     

Tumor proliferation, p53 expression, and apoptosis in laryngeal carcinoma: relation to the results of radiotherapy

BACKGROUND: Radiotherapy is used in the treatment of laryngeal carcinoma. The search for biologic parameters that could be used to identify patients who will respond to radiotherapy is crucial. The aim of this study was to determine whether the Ki-67 and p53 indices and the pretreatment apoptotic index would be useful in predicting local control and survival for a group of laryngeal carcinoma patients given postoperative radiotherapy. METHODS: Fifty-seven patients with laryngeal carcinoma treated between 1988 and 1993 were included in this study. Postoperative radiotherapy was given to a mean dose of 57.7 gray (Gy) (range, 50-68; median, 60) in 2-Gy daily fractions. Ki-67 and p53 immunostaining were performed on paraffin-embedded tissue. Cells were evaluated for apoptosis using hematoxylin and eosin-stained slides. Clinicopathologic tumor characteristics were studied in relation to Ki-67, p53, and apoptotic indices, and as prognostic factors for local control and survival in both univariate and multivariate analysis. RESULTS: The Ki-67, p53, and pretreatment apoptotic indices were not related to any clinicopathologic tumor characteristics. Five-year actuarial local control for the whole group was 47%. Patients with tumors that had low Ki-67 proliferation had better long term local control (P < 0.01). and survival (P < 0.03). p53 expression was not predictive of local control or survival in this study. Patients with tumors that had low pretreatment apoptotic indices had better local control (P < 0.049) and survival (P < 0.056) than patients with highly apoptotic tumors. Tumor extension and the pretreatment apoptotic index were significant predictive factors for local control and survival in multivariate analysis. CONCLUSIONS: Ki-67 proliferation measurement and the pretreatment apoptotic index are useful in predicting the clinical outcome of laryngeal carcinoma patients referred for radiotherapy. The role of p53 oncoprotein determination in predicting these outcomes is unclear. Assessment of biologic tumor characteristics could aid in the selection of patients for different treatment strategies.     

Can pretreatment computed tomography predict local control in T3 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy?

PURPOSE: To determine if pretreatment computed tomography (CT) can predict local control in T3 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy (RT). METHODS AND MATERIALS: Forty-two patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated for cure with RT alone; all had a minimum 2-year follow-up. Tumor volumes and extent were determined by consensus of two head and neck radiologists on pretreatment CT studies. A tumor score was calculated and assigned to each primary lesion depending on the extent of laryngeal spread. Sclerosis of any laryngeal cartilage was recorded. The specific CT parameters assessed were correlated with local control. RESULTS: Tumor volume was a significant predictor of local control. For tumors measuring < 3.5 cm3, local control was achieved in 22 of 26 patients (85%), whereas for tumors > or = 3.5 cm3, local control was achieved in 4 of 16 patients (25%) (p = 0.0002). Sensitivity and specificity using this cutpoint were 85% and 75%, respectively. Tumor score as a measure of anatomic extent was also found to be a significant predictor of local control. The local control rate for tumors assigned a low tumor score (< or = 5) was 78% (21 of 27) compared to 33% (5 of 15) for tumors assigned a high tumor score (6, 7, or 8) (p = 0.008). A significant decrease in the local control rate was observed for cancers involving the paraglottic space at the false vocal cord level (14 of 16 [88%] vs. 12/26 [46%]) (p = 0.010), cancers involving the face of the arytenoid (15 of 18 [83%] vs. 11 of 24 [46%]) (p = 0.024), and tumors involving the interarytenoid region (25 of 36 [69%] vs. 1 of 6 [17%]; p = 0.020). There were 12 patients with sclerosis of both the ipsilateral arytenoid and the adjacent cricoid cartilage. These patients showed a significant decrease in local control (4 of 12 [33%]). CONCLUSION: Pretreatment CT can stratify patients with T3 glottic carcinoma into groups more or less likely to be locally controlled with definitive RT. The local control rate for these tumors can be improved using a CT-based tumor profile; the ideal CT profile for a radiocurable T3 glottic larynx carcinoma is volume < 3.5 cm3 and no or single laryngeal cartilage sclerosis.     

Osmolyte contents of cultured astrocytes grown in hypoosmotic medium

The prognostic value of p53 protein overexpression was investigated in a large series of early stage endometrial carcinomas with long follow-up (n=179, median follow-up 147 months). P53 overexpression was detected in 10 cases (5.6%). At the end of the study period, 30% (3/10) of patients with p53 protein overexpression had died of their disease compared to 6.5% (11/169) of those without overexpression. Multivariate analysis revealed that only myometrial invasion (RR 2. 1; 95% CI=1.2-3.6; P=0.001) and p53 overexpression (RR 9.5; 95% CI=2. 5-36.8; P=0.007) were independent predictors of survival. These results suggest that immunohistochemical evaluation of p53 protein overexpression provides strong prognostic information for the outcome of endometrial carcinoma patients with early stage disease.     

Multivariate analysis results of radiotherapy for laryngeal cancer

We assess the impact of radiotherapy in the treatment of laryngeal cancer and evaluate the value of the standard dose (linear quadratic plus time model) and other variables to predict tumor control and survival. Between 1972 and 1989, 80 patients with laryngeal cancer received comprehensive radiotherapy. Patients with stage I laryngeal glottic cancer (T1-N0-M0) were excluded from this study. Mean follow-up was 15 months (range 4 to 181). The mean age was 64.8 years (range 40 to 92). Standard dose varied from 32.65 to 81.81 Gy (mean 66.78). The 5-year overall survival and tumor-specific survival rates were 44.9 +/- 5.8% and 51.4 +/- 5.9%, respectively. Five-year local control and locoregional control rates were 66.4 +/- 5.7% and 61.9 +/- 5.8%, respectively. Multivariate analysis showed that local control was significantly predicted by T stage (p = .032), but not by standard dose (p = .906). Independently significant factors predicting tumor-specific survival included stage (p = .006), site (p = .019), and age (p = .001). Local control and survival were significantly predicted by the TNM-staging classification. The standard dose did not predict local recurrence or survival.     

Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers

PURPOSE: To investigate the prognostic and predictive value of c-erbB-2 overexpression in breast cancer in relation to other prognostic markers. PATIENTS AND METHODS: Paraffin-embedded tumors from 315 consecutive primary breast cancer patients were screened for c-erbB-2 protein (p185) overexpression by immunohistochemistry using the monoclonal antibody CB11. RESULTS: c-erbB-2 protein overexpression was detected in 19% of tumors and was associated with shorter 5-year overall survival (OAS) rate compared with c-erbB-2-negative cases in the total patient material (58% and 77%, respectively; P = .004) and in the 96 node-positive patients (31% and 61%, respectively; P = .02), but not in node-negative patients. For 47 node-positive patients treated with adjuvant tamoxifen and radiotherapy, the 5-year OAS was 13% for c-erbB-2 overexpression and 75% for c-erbB-2-negative patients (P = .00004). The frequency of c-erbB-2 overexpression decreased with age at diagnosis. The prognostic value of c-erbB-2 on OAS was independent of age, node status, tumor size, histopathologic grade, hormone receptor status, S phase, p53 status, and adjuvant treatment. c-erbB-2 status added prognostic information to p53-negative and low S-phase cases, but not to p53-positive and high S-phase cases. Correspondingly, these only added information to c-erbB-2-negative cases. CONCLUSION: c-erbB-2 protein overexpression may have a predictive value with regard to adjuvant therapy in node-positive patients, for whom adjuvant tamoxifen with radiotherapy appears insufficient in the presence of c-erbB-2 overexpression. Combination of conventional and newer tumor markers may identify patients with a worse prognosis within groups with a generally favorable prognosis.     

Carcinoma of the tonsillar fossa: prognostic factors and long-term therapy outcome

PURPOSE: To identify prognostic parameters and evaluate the therapeutic outcomes for patients with carcinoma of the tonsillar fossa treated with three treatment modalities. METHODS AND MATERIALS: The results of therapy are reported in 384 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 154 were treated with irradiation alone (55-70 Gy), 144 with preoperative radiation therapy (20-40 Gy), and 86 with postoperative irradiation (50-60 Gy). The operation in all but four patients in the last two groups consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection. RESULTS: Treatment modality and total irradiation doses had no impact on survival. Actuarial 10-year disease-free survival rates were 65% for patients with T1 tumors, 60% for T2, 60% for T3, and 30% for T4 disease. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better disease-free survival (60% and 70%, respectively) at 5 years than those with large or fixed lymph nodes (30%). Primary tumor recurrence (local, marginal) rates in the T1, T2, and T3 groups were 20-25% in patients treated with irradiation and surgery and 31% for those treated with irradiation alone (difference not statistically significant). In patients with T4 disease treated with surgery and postoperative irradiation, the local failure rate was 32% compared with 86% with low-dose preoperative irradiation and 47% with irradiation alone (p = 0.03). The overall recurrence rates in the neck were 10% for N0 patients, 25% for N1 and N2, and 35-40% for patients with N3 cervical lymph nodes, without significant differences among the various treatment groups. The incidence of contralateral neck recurrences was 8% with the various treatment modalities. On multivariate analysis the only significant factors for local tumor control and disease-free survival were T and N stage (p = 0.04-0.001). Fatal complications were noted in 7 of 144 (5%) patients treated with preoperative irradiation and surgery, 2 of 86 (2%) of those receiving postoperative irradiation, and 2 of 154 (1.3%) patients treated with radiation therapy alone. Other moderate or severe nonfatal sequelae were noted in 30% of the patients treated with preoperative irradiation and surgery, in 53% treated with postoperative irradiation, and in 19% receiving radiation therapy alone. CONCLUSION: Primary tumor and neck node stage are the only significant prognostic factors influencing locoregional tumor control and disease-free survival. Treatment modality had no significant impact on outcome. Radiation therapy remains the treatment of choice for patients with stage T1-T2 carcinoma of the tonsillar fossa. In patients with T3-T4 tumors and good general condition, combination surgery and postoperative irradiation offers better tumor control than single-modality and preoperative irradiation procedures, but with greater morbidity.     

Glutamate release in the nucleus tractus solitarius induced by peripheral lipopolysaccharide and interleukin-1 beta

PURPOSE: The selection of therapy for stage T1 bladder cancer is controversial, and reliable biomarkers that identify patients likely to require cystectomy for local disease control have not been established. We evaluated our experience with T1 bladder cancer to determine whether early cystectomy improves prognosis, and whether microvessel density has prognostic value for T1 lesions and could be used for patient selection. MATERIALS AND METHODS: We retrospectively reviewed the records of 88 patients with T1 transitional cell carcinoma of the bladder. Patient outcome was correlated with therapeutic intervention. Paraffin embedded tissue from 54 patients was available for factor VIII immunohistochemical staining for microvessel density quantification. RESULTS: Median followup was 48 months (range 12 to 239). Of the patients 34% had no tumor recurrence. The rates of recurrence only and progression to higher stage disease were 41 and 25%, respectively. The survival of patients in whom disease progressed was diminished (p = 0.0002). Grade did not predict recurrence or progression nor did cystectomy provide a survival advantage. Microvessel density did not correlate with recurrence or progression. CONCLUSIONS: Patients with T1 bladder cancer have a high risk of recurrence and progression. Tumor progression has a significant negative impact on survival. Neither grade nor early tumor recurrence predicted disease progression. Because early cystectomy did not improve patient outcome, we suggest reserving cystectomy for patients with progression or disease refractory to local therapy. Microvessel density is not a prognostic marker for T1 bladder cancer and has no value in selecting patients with T1 disease for cystectomy.     

Radiotherapy and local control in rectal cancer

Recurrence is a stage in the natural history of rectal cancer. Preoperative radiotherapy or postoperative radiochemotherapy lower the rate of recurrence, improving local control. From 1980 to 1997, at the "Divisione di Radioterapia" of the "Università Cattolica del S. Cuore" of Rome 380 patients with rectal cancer of early clinical stage T2-3, candidates for surgery for cure, underwent radiation therapy. 119 patients underwent postoperative radiotherapy (45-50 Gy); 45 patients underwent "sandwich" radiotherapy (45 Gy:27 Gy before and 28 Gy after surgery), of whom 7 were treated with preoperative radiotherapy alone; 145 patients underwent preoperative concomitant radiochemotherapy according to 3 different protocols, radiotherapy (38 Gy) combined with mitomycin C and 5-FU; radiotherapy (50.4 Gy) combined with cisplatin and 5-FU; radiotherapy (45 Gy) combined with 5-FU and folinic acid. 71 patients were treated with preoperative radiotherapy (38 Gy) combined with IORT (10 Gy). Median follow-up was 6 years. Overall local control was 85% at 3 years, 83% at 5 years, 81% at 10 years. The rate of local control at 5 years was: 76% for postoperative radiotherapy, 83% for "sandwich" radiotherapy, 84% for preoperative radiochemotherapy and 93% for preoperative radiotherapy combined with IORT. Local control was shown to be significantly better with preoperative treatment as compared to postoperative treatment (p = 0.02). The incidence of metastases was 35% in the patients with local recurrence and 16% in those with local control. The difference in survival was highly significant in patients with local control as compared to those with local recurrence: at 5 years 87% and 32% respectively. Patients with local control showed a lower incidence of metastasis and a better survival.     

Radiation therapy for early stage (T1-T2) sarcomatoid carcinoma of true vocal cords: outcomes and patterns of failure

Sarcomatoid carcinoma of head and neck mucosal sites is a rare high-grade malignancy that may cause diagnostic and therapeutic controversies. A characteristic of this entity consistently reported but not entirely validated is its relative radioresistance and the general belief is that surgery is the treatment of choice. The objective of this retrospective study was to determine if patients treated with radiation for early glottic sarcomatoid carcinoma had worse outcomes than those achieved with irradiation for the more typical squamous cell carcinoma. Twenty-eight cases of early stage (T1-T2) sarcomatoid carcinoma of the larynx treated with definitive doses of megavoltage irradiation between 1969 and 1995 at The University of Texas M. D. Anderson Cancer Center form the cohort for this analysis. All pathologic material was reviewed to confirm the diagnosis. All tumors manifested spindle cell features with marked cytomorphologic abnormalities characteristic of this entity. Sixteen tumors (57%) had the more typical polypoid gross morphology of sarcomatoid carcinoma. Twenty-one patients (75%) were staged T1 and seven patients (25%) had stage T2 disease. All patients were treated with small laryngeal fields, median size 20 cm2, and to a median dose of 65 Gy. Follow-up ranged from 1.5 to 24 years (median, 10 years). Four patients (14%) had local disease recurrence, and all had salvage total laryngectomies and remained free of local disease. The 5-year actuarial local control rates for patients with T1 and T2 lesions were 94% and 54%, respectively. Only one patient developed regional and distant disease. The 10-year actuarial disease-specific and overall survival rates were 92% and 63%, respectively. Patients with early stage sarcomatoid carcinoma of the glottis treated with radiation had similar control rates to irradiated patients with similar volume disease with the more typical squamous cell carcinoma. The authors contend that the histologic diagnosis of sarcomatoid carcinoma by itself should not influence the decision to treat a patient with early stage glottic disease with irradiation.     

Signal-averaged electrocardiogram in patients with insulin-dependent (type 1) diabetes mellitus with and without diabetic neuropathy

The medical charts and operative files of 112 patients (combined inception cohort) with well to moderately differentiated invasive glottic squamous cell carcinoma presenting fixation (22) or impaired motion (90) of the true vocal cord (TVC) consecutively treated with cricohyoidoepiglottopexy (CHEP) at our institutions from 1972 to 1989 were retrospectively reviewed. A minimum 5-year follow-up was always achieved. The Kaplan-Meier 5-year actuarial survival, local recurrence, nodal recurrence, distant metastasis, and metachronous second primary tumor estimate for the entire group of patients were 84.7%, 5.4%, 6.4%, 1.2%, and 10.8%, respectively. The 5-year absolute and cause-specific survival rates were 85.5% and 94.1% for patients with fixation of the TVC and 81.3% and 96% for patients with impaired motion of the TVC. The 5-year actuarial local control rates for patients with fixation or impaired motion of the TVC were 95.4% and 94.4%, respectively. Local recurrence was statistically more likely in patients with positive margins (p = .007). Nodal recurrence was statistically more likely in patients with local recurrence (p = .005). Permanent tracheostomy related to postoperative laryngeal stenosis was requested in 2 patients. Aspiration-related completion total laryngectomy and/or permanent gastrostomy were never requested. Overall, local control and laryngeal preservation were achieved in 97.3%, and 95.5% of patients, respectively. At our institutions, the change from the conservative treatment modalities of radiotherapy and vertical partial laryngectomy to CHEP has brought about an increase in long-term survival, local control, and laryngeal preservation rates when compared to historical controls using vertical partial laryngectomy or radiotherapy.     

CO2 laser treatment; an effective and minimally disruptive endoscopic therapy for small glottic laryngeal carcinomas

OBJECTIVE: To evaluate endoscopic CO2 laser vaporization as a treatment of small glottic laryngeal carcinomas selected by means of video laryngo-stroboscopy. DESIGN: Prospective. SETTING: ENT department, University hospital, Free University Amsterdam. METHODS: Patients with a small glottic laryngeal carcinoma (stage Tis or T1a), were selected by means of video-laryngo-stroboscopy for a single stage endoscopic CO2 laser vaporization treatment as an alternative for radiotherapy. They were followed up for at least 24 months. RESULTS: Three of the 46 patients (6%) developed a local recurrence within 2 years; one of these could be treated once more with the CO2 laser, the other two were irradiated. None of these patients developed metastases in cervical lymph nodes or distant metastases. Most patients (41, 89%) assessed their voices after CO2 laser vaporization as normal or almost normal. Slight dysphonia was reported by five patients (11%). No serious dysphonia or aphonia occurred. CONCLUSION: Endoscopic CO2 laser vaporization, compared with radiotherapy or more extensive surgery, constitutes an adequate treatment for selected patients with small glottic laryngeal carcinomas. As a result of this treatment, it will be possible to preserve the larynx in more patients.     

Comparison of radiotherapy and surgical results of early stage glottic cancer: a retrospective analysis

From March 1977 to October 1989, 85 patients with early stage glottic cancer were treated with either radiotherapy or surgery at Chang Gung Memorial Hospital (CGMH). Patients were excluded from the analysis of local control if they died or remained disease-free with a follow-up period of less than two years. Of the 26 patients treated with definitive radiotherapy, initial control of the primary lesions was achieved in 100% of stage T1s, 76% of T1, and 57% of T2 patients. Surgical salvage of radiation failure was achieved in 83% of the patients, giving the ultimate local control of 100% for T1s, 94% for T1, 86% for T2 patients. Of the 44 patients treated with definitive surgery, initial control of the primary lesions was achieved in 100% for T1s, 95% for T1, and 78% for T2 patients. Salvage of the surgical failure was 50%, giving the ultimate control in this group of 100% for T1s, 95% for T1, 83% for T2. There was no difference in either initial or ultimate control of T1 and T2 lesions between patients treated with primary radiotherapy and primary surgery. Voice preservation rates were 73% and 34% in the radiotherapy and surgery group, respectively. When divided into two groups according to the times they were being treated, we found that surgery preserved a comparable number of larynges as radiotherapy did after 1988 (60% vs 77%, p = 0.33). It is concluded that radiotherapy and surgery could achieve the same good local control results and long-term survival and comparable functional results of early stage glottic cancer, if conservative surgery is carefully selected for each patient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of radiation therapy fraction size on local control of early glottic carcinoma

PURPOSE: Different radiotherapy fractionation schedules were used over a 10-year period to treat patients with early squamous cell carcinoma of the vocal cords at McGill University. A retrospective analysis was performed to study the effect of fraction size on local control in this group of patients. METHODS AND MATERIALS: A total of 126 previously untreated patients with T1 invasive squamous cell carcinoma of the true vocal cords were irradiated between January 1978 and December 1988 in the Department of Radiation Oncology at McGill University. All patients received megavoltage irradiation, 94 patients received daily fractions > 2 Gy (64 patients received 50 Gy with once-daily 2.5-Gy fractions, and 30 received 65.25 Gy in 29 fractions of 2.25 Gy each), and 32 patients were treated to a dose of 66 Gy in 33 fractions with 2 Gy/fraction. Patients' characteristics of prognostic importance were equally distributed between the two fractionation groups. RESULTS: At a median follow-up of 84 months, the 10-year disease-free survival and overall survival were 76% and 93%, respectively. Local control for patients treated with > 2 Gy fraction was 84%, compared to 65.6% for those treated with 2-Gy fractions (p = 0.026). Among the prognostic factors tested, such as gender, age, stage, anterior and posterior commissure involvement, smoking history, and fraction size, the latter was the only significant predictor of local control for the whole group of patients in univariate (p = 0.041) and multivariate (p = 0.023) analysis. There was no observed difference in the incidence of complications between the two fractionation groups. CONCLUSIONS: From the results of this retrospective review of patients treated with radiotherapy for T1 true vocal cord cancer, and within the range of total doses and overall treatment times used in our patients, it was found that fractionation schedules using daily fraction size > 2 Gy are associated with a better local control than schedules delivering 2 Gy/fraction, with no increase in toxicity.     

Sensitization of olfactory guanylyl cyclase to a specific imprinted odorant in coho salmon

PURPOSE: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. METHODS AND MATERIALS: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. RESULTS: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). CONCLUSION: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and may improve overall survival in certain subgroups. As salvage rates after developing local recurrence are poor adjuvant vulvar radiation should be considered for patients at risk after primary surgery.     

Relationship of tumor angiogenesis and nuclear p53 accumulation in invasive bladder cancer

The purpose of this investigation was to evaluate the relationship between tumor angiogenesis and nuclear p53 accumulation in invasive bladder cancer. We studied 161 patients with invasive transitional cell carcinoma of the bladder who had previously undergone radical cystectomy. Analysis was performed to determine the presence of p53 nuclear accumulation and extent of tumor-associated angiogenesis. p53 status identified a group of patients at high risk for tumor progression (p53-altered tumors), and microvessel density determinations added additional prognostic information by identifying a subset of aggressive tumors within the wild-type p53 subgroup. At 5 years, patients with tumors exhibiting no evidence of p53 alterations and low microvessel counts demonstrated 3% recurrence and 88% survival, compared to 43% recurrence and 59% overall survival for patients with intermediate vessel counts and 61% recurrence and 43% overall survival for patients with the highest vessel counts (P < 0.001 and P = 0.003, respectively). Angiogenesis also provides additional prognostic information to patients with tumors that demonstrate p53 alterations. An association between angiogenesis and p53 status did exist (P = 0. 05); however, 27% of the tumors that showed no evidence of p53 alterations exhibited high microvessel counts, and 26% of tumors with evidence of p53 alterations had low microvessel counts. Tumor-associated angiogenesis adds additional useful prognostic information to that which is obtained from p53 status in patients with invasive transitional cell carcinoma of the bladder. Although an association between p53 status and the degree of angiogenesis was identified, other factors appear to play a role in the regulation of tumor-induced neovasularization.     

Surgery versus surgery and postoperative radiotherapy in squamous cell carcinoma of the buccal mucosa: a comparative study

BACKGROUND: The efficacy of postoperative radiotherapy for squamous cell carcinoma of the buccal mucosa was evaluated. METHODS: One hundred seventy-six patients treated between 1989 and 1993 were analyzed. One hundred fifteen patients were treated with surgery alone (Group 1), and 61 patients were treated with a combination of surgery and postoperative radiotherapy (Group 2). RESULTS: Actuarial 3-year locoregional control in Groups 1 and 2 was 11% and 48% for patients with stage III + IV cancer (P = .001) and 71% and 75% for patients with stage I + II cancer (P = .74), respectively. On multivariate analysis for locoregional failure, surgical margin, bone invasion, high grade, and node involvement were significant factors in Group 1, whereas in Group 2 only tumor thickness was a significant factor. For local failure, margin, bone invasion, and stage in Group 1 and tumor thickness in Group 2 appeared as significant factors. For nodal failure, clinical nodal (cl N0 vs. N+) stage and grade in Group 1 and pathologic nodal stage (pN0 + 1 vs. pN2) in Group 2 were observed as significant factors. On subset analysis, postoperative radiotherapy was observed to have a significant advantage for surgical margins of 2 mm or less in both early pT (T1 + T2) (P = .019) and late pT (T3 + T4) (P = .016) stages. The local failure rate was higher if the time between surgery and radiotherapy was greater than 30 days. CONCLUSIONS: Postoperative radiotherapy was effective in decreasing locoregional failure in patients with close surgical margins, tumor thicker than 10 mm, high-grade tumors, positive node, and bone invasion. The effect of interval between surgery and postoperative radiotherapy on local failure was margin-dependent.