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Tumor radiosensitivity (SF2) is a prognostic factor for local control in head and neck cancers.

PURPOSE: To evaluate prospectively the prognostic value of SF2 for local control and survival in patients undergoing radiation therapy for head and neck cancers. METHODS AND MATERIALS: Following informed consent tumor specimens were obtained from 156 patients with primary carcinomas of the head and neck region. The specimens were assessed for the ability to grow in vitro (colony forming efficiency, CFE) and inherent radiosensitivity measured as the surviving fraction at 2 Gy (SF2) using a soft-agar clonogenic assay. Patients were treated mainly with neoadjuvant chemotherapy plus radiation therapy usually as a combination of accelerated external beam and interstitial radiotherapy. The probabilities of local control and survival were analyzed by univariate, bivariate and Cox multivariate analyses. RESULTS: Successful growth was achieved in 110/156 specimens and SF2 values were obtained from 99/156. Eighty four out of these patients underwent radical treatment. The median SF2 value for the 84 tumors was 0.40. At a mean follow-up time of 25 months (range 7-65) the median SF2 value of tumors from 14 patients who developed local recurrence was 0.53, which was significantly higher than the median of 0.38 for tumors from 70 patients without local recurrence (p = 0.015). Tumor SF2 was a significant prognostic factor for local control (p = 0.036), but not for overall survival (p = 0.20). Tumor SF2 was an independent prognostic factor for local control within bivariate and Cox multivariate analyses. CONCLUSIONS: This study has shown that tumor radiosensitivity measured as SF2 is a significant prognostic factor for local control in head and neck cancers.

Adult↗

Tumor volume as determined by computed tomography predicts local control in hypopharyngeal squamous cell carcinoma treated with primary surgery.

Computed tomography reliably evaluates hypopharyngeal squamous cell carcinomas (SCC) regarding the infiltration of specific anatomic structures and tumor volumes, both of which have been shown to be predictors of local control in patients treated with radiation therapy alone. However, an association of specific infiltrated structures and/or tumor volume with local control has not been investigated for surgical treatment; thus, we determined relationships of various infiltrated anatomic structures and tumor volume with local control in patients with hypopharyngeal SCC treated with primary surgery. In 45 hypopharyngeal SCC, tumor volumes were measured by pretreatment CT, and extent of tumor infiltration was determined by postoperative pathologic examination. All patients had clinical follow-up for recurrent tumor at the primary site. Statistical analysis basically consisted of chi-square and U-tests. Local control rate was 84.4% (38 of 45). Tumor volume was significantly associated with local control (p=0.004). Six of 16 (38%) patients with tumor volumes > or =8.1 cm3 (mean) had a local recurrence, which is significantly (p=0.003) more compared with 1 of 29 (3%) in the group of patients with volumes <8.1 cm3. Among all evaluated anatomic structures, only a tendency for significant association with local control was found for tumor involvement of the tonsils and the extralaryngeal soft tissues. The determination of tumor volumes by CT helps predict local control in patients with hypopharyngeal SCC treated with primary surgery.

Adult↗

The effect of overall treatment time of radiation therapy on local control of T1-stage squamous cell carcinoma of the glottis.

From 1975 to 1990, 72 patients with T1 glottic cancer, excluding a verrucous type of carcinoma, were treated with radiation therapy (RT). All treatments were given with a standard fractionation of 2 Gy per day. The total dose to the tumor ranged from 60 to 70 Gy. Six patients received a split-course RT. The overall local control rate was 87% at 5 years. Forty-one patients who completed RT in 45 days or less had a 5-year local control rate of 95%. Sixteen patients who completed a treatment course in 46 to 49 days had a local control rate of 81%. Fifteen patients with a treatment course of more than 50 days had a local control rate of 73%. There was a statistically significant difference in local control rates among the three groups (P<.05). The split-course RT group had a 5-year local control rate of 50%; that rate was statistically significantly inferior to that of the continuous course group (P<.001). Multivariate analysis also showed that an interruption of the treatment course was an important parameter in relation to the local control. The prolongation of standard RT schedules adversely affected local control of T1 glottic carcinoma and, therefore, should be avoided whenever possible.

Carcinoma, Squamous Cell↗

Local control assessment in clinical oncology.

The true significance of achieving local control has been a matter for debate among clinical oncologists for many years and still is for those tumors where distant metastases are the major cause of failure and mortality. The assessment of local control appears elusive as it may be conceived as the local eradication of neoplastic cells while this should be confirmed by no risk for recurrence. Tools and procedures are available to assess separately the local response after treatment and at long term. Direct methods are quite different according to the different clinical and pathologic conditions. Complete local responses may be followed by recurrence leading to a different approach: to wait for the appearance of recurrence rather than to pursue a complete response. The diagnostic clinical and instrumental methods while easy in superficial tumors, are complex, expensive and poorly reliable in deep-seated tumors. Thus, in general, any assessment of local control in terms of diagnostic work-up can frequently be difficult and misleading.

Breast Neoplasms↗

Effect of tumor bulk on local control and survival of patients with T1 glottic cancer.

PURPOSE: To evaluate the effect of tumor bulk in relation to various tumor-related prognostic factors and treatment-related variables on local control and survival of patients with T1 N0 M0 squamous cell carcinoma of the glottis. MATERIALS AND METHODS: In 114 patients with T1 squamous cell carcinoma of the glottic larynx who were irradiated with curative intent, we determined the effect of tumor bulk in relation to mucosal extent (stage and anterior commissure involvement), histologic differentiation and various radiation factors, especially overall treatment time on local control and survival. Tumors were classified retrospectively as small surface lesions or bulky tumors. Seventy-seven patients had small lesions and 37 had bulky tumors. The anterior commissure was involved with cancer in 43 patients. The overall duration of irradiation ranged from 39 to 64 days. The median follow-up time was 6 years (range 5-24 years). RESULTS: The 5-year actuarial local control rate for all patients was 82% after radiotherapy and 92% after salvage laryngectomy. On univariate analysis, bulky tumors and tumors involving the anterior commissure showed an adverse effect on local control, whereas the overall duration of irradiation had a borderline significance. The actuarial local control rate was 91% for small tumors and 58% for bulky tumors (P = 0.0002), 88% when the anterior commissure was not involved and 67% when the anterior commissure was involved (P = 0.01) and 89% when radiation was given in less than 50 days and 73% when irradiation exceeded 50 days (P = 0.06). On multivariate analysis. tumor bulk was the only significant factor that affected local control (P = 0.02). The 5-year actuarial survival for all patients was 73% and the disease-free survival was 92%. CONCLUSION: This study shows that tumor bulk has a highly significant effect on the radiation control of T1 glottic cancer. Patients who had bulky tumors had lower local control and disease-free survival rates than those patients who had small tumors.

Adult↗

Radiotherapy, local control and survival in cervical carcinoma.

The natural history of cervical carcinoma is characterized by a close correlation between local control and survival. Local eradication of the disease is justified for the obvious impact on the quality of life as well as on long-term survival. A series of analyses carried out in the last decades have elucidated the role of a number of prognostic factors in local control. Among treatment modalities applied to attain this aim, particular interest has been focused in recent years on concomitant radiation and chemotherapy. While some experiences have shown promising results, the precise role of this combination will be defined based on the outcomes of some randomized studies now in progress. Among the modalities of concomitant radiation and chemotherapy, some authors have proposed the following sequence: neoadjuvant chemotherapy and surgical resection. It is an aggressive approach potentially associated to major side-effects. This therapeutic modality will require an accurate assessment of clinical results both in terms of clinical response, local control and effects on organ function and quality of life.

Antineoplastic Agents↗

Tumor excision and radiotherapy as primary treatment of breast cancer. Analysis of patient and treatment parameters and local control.

From 1966 to 1979, 235 patients with operable breast cancer were treated by tumor excision and radiotherapy. The actuarial survival at 10 years was 94.8% for stage I and 58% for stage II tumors. Local recurrent cancer was seen in 23/235 patients and was related to T stage, N stage, width of surgical excision, radiation dose to the tumor bed and anatomopathological differentiation. Recurrences were seen in 1/7 of T0, 3/57 (5.2%) of T1, 11/102 (10.8%) of T2 and 2/6 of T3 tumors. Local control in the breast decreased significantly in N1b cases (p = 0.005) or when 3 or more axillary lymph nodes were positive (p = 0.0074). Local control after segmentectomy or tumorectomy was identical. However, a poorer local control was found in 20 cases treated with subtotal resection (p less than 0.05). A clear dose-local control relationship was found in this material, with a 100% local control in all T0, T1 tumors which received more than 1800 ret and all T2 tumors which received more than 2000 ret. As 19 of 23 breast recurrences were seen at the primary site in the breast we believe that booster doses should be given in order to maximise local control.

Adult↗

Radiation therapy in early glottic carcinoma: uni- and multivariate analysis of prognostic factors affecting local control.

PURPOSE: The purpose of this report is to clarify prognostic factors affecting local control of T1 and T2 glottic tumors and to define an optimal regimen for radiation therapy. METHODS AND MATERIALS: Two hundred and ten patients (199 males, 11 females, age range 30 to 86 years with an average of 62 years) with previously untreated invasive squamous cell carcinoma of the glottis were treated with radiation therapy at the University of Tokyo between January 1972 and December 1989. Endoscopic microsurgery was introduced as an integral part of treatment in 1974. From 1974 to 1979 the radiation dose was gradually reduced, reaching a mean of 20 Gy in 2 weeks in 1979. From 1980 to 1983, the total dose increased to 50.4 Gy, with a fraction size of 1.8 Gy, over a mean of 5.6 weeks. From 1984 onward, the mean total radiation dose increased to 60 Gy with a fraction of 2 Gy. RESULTS: Recurrence-free 5 year survival rates for T1a, T1b, and T2 were 79%, 73%, and 67%, respectively. When the relationship between radiation dose and local control rates was analyzed for each year from 1974 to 1989, total doses were strongly associated with local control for patients with T1a disease. Age, sex, daily dose, total dose, radiation machine (Co-60 or 10 MV Lineac), treatment technique (anterior wedged pair or parallel opposed fields), treatment volume, use of endoscopic microsurgery, and involvement of the anterior commissure were examined for effects upon relapse-free survival in T1a disease by uni- and multivariate analysis. Total dose was the only significant factor for T1a disease (p < 0.02). The effect of these variables upon relapse-free survival in T2 disease as well as the effect of cord mobility, and number of involved sites was examined by multivariate analysis. Total dose (p < 0.03), cord mobility (p < 0.05), and number of involved sites (p < 0.04) significantly affected relapse-free survival in T2 disease. CONCLUSION: At least 50 Gy is required for treatment of T1 disease when 2 Gy is used as a daily dose, even if endoscopic microsurgery is performed. Better local control of T2 disease in patients with impaired cord mobility or more than three involved sites leads to an improved prognosis; we recommend doses of at least 70 Gy or use of hyperfractionation in such patients with these factors. Although the daily dose did not significantly affect prognosis in multivariate analyses, 1.8 Gy is not recommended for treatment of T2 tumors instead of 2 Gy.

Adult↗

Local control in T3 laryngeal cancer treated with radical radiotherapy, time dose relationship: the concept of nominal standard dose and linear quadratic model.

In a retrospective study of the Dutch cooperative head and neck group 104 evaluable patients with T3NxMO squamous cell carcinoma of the larynx were treated primarily with a full course of radiotherapy. The results of treatment are presented in terms of locoregional control. The actuarial 3-year local control rate was 53%. Regional control was 77% for node positive patients and 96% for N0 patients (p = 0.01). Surgical salvage was successful in 53% of cases with a local recurrence and in 3/8 regional recurrences, resulting in an ultimate locoregional control rate of 83% for N0 patients and 68% for N+ patients. A uni- and multivariate analysis of local control rate versus total dose, nominal standard dose, and extrapolated response dose has been done. To calculate extrapolated response dose the linear quadratic equation was used, assuming an a/b of 10 and a potential doubling time of clonogenic cells of 3, 5, and 7 days. In multivariate analysis the extrapolated response dose with a potential doubling time of 5 days was the only independent prognostic factor for local control (p = 0.069) and ultimate locoregional control (p = 0.0015). Nominal standard dose showed no dose-response relationship. Based on the S-shaped dose response curve, using the LQ model, several therapeutical options are discussed.

Aged↗

Impact of systemic treatment on local control for patients with lymph node-negative breast cancer treated with breast-conservation therapy.

PURPOSE: To determine the impact of tamoxifen and chemotherapy on local control for breast cancer patients treated with breast-conservation therapy. PATIENTS AND METHODS: The data from 484 breast cancer patients who were treated with breast-conserving surgery and radiation were analyzed. Only patients with lymph node-negative disease were studied to provide comparative groups with a similar stage of disease and a similar competing risk for distant metastases. Actuarial local control rates of the 277 patients treated with systemic therapy (128, chemotherapy with or without tamoxifen; 149, tamoxifen alone) were compared with the rates for the 207 patients who received no systemic treatment. Only 10% of the patients had positive (2%), close (3%), or unknown margin status (5%). RESULTS: Patients treated with systemic therapy had improved 5-year (97.5% v 89.8%) and 8-year (95.6% v 85.2%) local control rates compared with those that did not receive systemic treatment (P =.004, log-rank test). There was no statistical difference in local control between patients treated with chemotherapy and patients treated with tamoxifen alone (P =.219). Systemic treatment, margin status, young patient age, estrogen and progesterone receptor status, and primary tumor size were analyzed in a Cox regression analysis. The use of systemic treatment was the most powerful predictor of local control: patients who did not receive systemic treatment had a relative risk of local recurrence of 3.3 (95% confidence interval, 1.5 to 7.5; P =.004). CONCLUSION: In this retrospective analysis, systemic therapy appears to contribute to long-term local control in patients with lymph node-negative breast cancer treated with breast-conservation therapy.

Adult↗

Local control of Ewing's sarcoma: an analysis of 67 patients.

Local control of Ewing's sarcoma was analysed in a series of 67 patients treated by surgery and/or radiotherapy as well as combination chemotherapy. Radiotherapy was employed with or without surgery in 60 patients and produced an overall local control rate of 55%; complete excision of the primary lesion seemed to be beneficial. There was a marked variation in control rates depending on the site of the primary lesion: limb 85%, rib 53%, pelvis 31% and other sites 33%. Primary tumours greater than 10 cm in diameter were significantly less likely to be controlled. Using daily fractions of approximately 180 cGy, total doses in excess of 6000 cGy seem more likely to produce serious late morbidity and may not increase the local control rate. No cases of second malignancy arising in irradiated tissue have been observed to date, but one patient developed acute lymphoblastic leukaemia.

Adolescent↗

Local control in medically inoperable lung cancer: an analysis of its importance in outcome and factors determining the probability of tumor eradication.

PURPOSE: For patients who are medically unable to tolerate a surgical resection for technically resectable non-small-cell lung carcinoma, radiation therapy is an acceptable alternative. We report on the effect of achieving local control of the primary tumor on survival end-points, and analyze factors that may influence local control. METHODS AND MATERIALS: We reviewed the records of 152 patients with medically inoperable non-small-cell lung carcinoma treated at our institutions. All patients had technically resectable lesions and no evidence of metastatic disease. Treatment was delivered using megavoltage irradiation to doses ranging from 45 to 75 Gy. RESULTS: For patients with tumors 3 cm or less, locally controlling the tumor significantly improved survival (p = .0371). Patients with T1 tumors had a higher probability of survival and disease-free-survival than patients with larger tumors if the primary tumor was locally controlled, but this survival advantage disappeared if the tumor was not controlled. Overall, patients with smaller tumors had a lower incidence of distant spread, but this association was maintained only when the primary tumor was controlled (36 month risk of 10%, 23%, and 57% for tumors < 3 cm, 3-4.9 cm, 5 cm or greater, respectively, p = .0027). For patients whose tumors were not controlled, there was no significant difference in the risk of distant dissemination by tumor size. Higher radiation doses influenced local control and metastatic spread. We observed no influence of the initial field size in the risk of local control and in the probability of survival. CONCLUSION: Radical radiation therapy is an effective treatment for small (T1 or < 3 cm) tumors when treated to doses of 65 Gy or more, and should be offered as an alternative to surgery in elderly or infirm patients. New therapeutic strategies to improve the local control rate should be considered for larger tumors, through the use of hyperfractionated treatment, endobronchial "boost" irradiation, and sensitizing chemotherapy agents.

Carcinoma, Non-Small-Cell Lung↗

Optimizing local control in soft tissue sarcoma of the extremity.

Extremity soft tissue sarcoma is a rare malignancy in which a high rate of local control can be achieved with multimodal regimens and without excessive treatment-related morbidity. This article reviews the current status of evaluation, staging, and local treatment of these tumors. Evidence shows that surgical approaches that maximize local control have little effect on the development of distant metastasis and overall survival. The goal of local treatment, therefore, is a balance of adequate local control with limb salvage and minimal therapeutic morbidity. A variety of limb-sparing approaches using various adjuvant modalities in addition to conservative resection are discussed, including reported local control and complication rates. Treatment paradigms are then presented for the management of extremity soft tissue sarcoma of varying stages. Further studies are needed to define precisely the role, type, and timing of chemotherapy and radiotherapy in addition to surgery in the management of this disease with respect to local control and distant metastasis.

Brachytherapy↗

Placebo-controlled clinical trial of meglumine antimonate (glucantime) vs. localized controlled heat in the treatment of cutaneous leishmaniasis in Guatemala.

Sixty-six Guatemalans with parasitologically proven cutaneous leishmaniasis were randomly and equally divided into 3 treatment groups: those receiving meglumine antimonate (Glucantime), 850 mg antimony/day im for 15 days; those receiving localized controlled heat from a radio-frequency generator, 50 degrees C for 30 sec, 3 treatments at 7 day intervals; and those receiving treatment with a placebo. Of 53 isolates identified, 40 were Leishmania braziliensis braziliensis and 13 were L. mexicana mexicana. Thirteen weeks after beginning treatment, the number of patients from each group with completely healed and parasitologically negative lesions were as follows: meglumine antimonate, 16 (73%); localized heat, 16 (73%); and placebo, 6 (27%). The cure rate for those with infections due to L. b. braziliensis in each group was as follows: meglumine antimonate, 11 out of 14 (79%); controlled heat, 9 out of 14 (64%); and placebo, 0 out of 11.

Adult↗

T1/T2 glottic cancer managed by external beam radiotherapy: the influence of pretreatment hemoglobin on local control.

PURPOSE: Pretreatment hemoglobin (Hb) level has been reported to be an important prognostic factor for local control and survival in various malignancies. However, in many settings, the adverse effect of a low Hb may be related to more advanced disease. The purpose of this analysis was to assess the influence of pretreatment Hb on local control in a large series of patients with a localized cancer (T1/T2 glottic cancer, AJCC 1992) treated in a standard fashion. MATERIALS AND METHODS: Between January 1981 and December 1989, 735 patients (median age 63; 657 males, 78 females) with T1/T2 glottic cancer were treated with radiation therapy (RT). The standard RT prescription was 50 Gy in 20 fractions over 4 weeks (97% of patients). Factors studied for prognostic importance for local failure included pretreatment Hb, age, sex, T category, anterior commissure involvement, subglottic extension, and tumor bulk (presence of visible tumor vs. subclinical disease). RESULTS: With a median follow-up of 6.8 years (range 0.2-14.3), 131 patients have locally relapsed for an actuarial 5-year relapse-free rate of 81.7%. The 5-year actuarial survival was 75.8%. The mean pretreatment hemoglobin level was 14.8 g/dl and was similar in all prognostic categories. On multivariate analysis, using the Cox proportional hazards model, pretreatment Hb predicted for local failure after RT. The hazard ratio (HR) for relapse was calculated for various Hb levels. For example, the HR for a Hb of 12 g/dl vs. a Hb of 15 g/dl was 1.8 (95% confidence interval 1.2-2.5). Previously established factors, including gender, T category, subglottic extension, as well as tumor bulk, were also prognostically important for local control. CONCLUSIONS: This analysis, in a large number of similarly treated patients, indicates that pretreatment Hb is an independent prognostic factor for local control in patients with T1/T2 carcinoma of the glottis treated with RT. The underlying biology of this observation needs to be explored, and using this information, it may be possible to develop strategies to improve treatment outcome.

Carcinoma, Squamous Cell↗

Issues in the local control of rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma (RMS) is a heterogeneous disease consisting of several different histologies arising from a variety of anatomic sites. Approximately half of the children who die of this tumor have failure at the primary site of involvement, making local control an important component of therapy. PROCEDURE: Published literature and newly analyzed data from the Intergroup Rhabdomyosarcoma Study Group (IRSG) regarding local control of RMS were reviewed. Information regarding the role of various local control modalities for different primary disease sites is presented along with new directions for clinical research. RESULTS: Local control rates for RMS average 80% for group III tumors, with large variations seen for different anatomic sites. Important gains in functional outcome for certain sites such as gynecologic system and bladder/prostate have been achieved by optimizing the use of the various treatment modalities. Local control at other sites such as the chest and extremities remains a problem. CONCLUSIONS: Advances in surgical and radiotherapy techniques coupled with multiagent chemotherapy are providing improved local control with decreasing morbidity. Optimal outcome is dependent on close collaboration between surgical, radiotherapy, and pediatric oncology specialists.

Antineoplastic Combined Chemotherapy Protocols↗

[Analysis of locally controlled esophageal carcinomas treated with radiotherapy].

Of 227 esophageal carcinomas treated with a radiation dose of 60 Gy or more, 100 patients had no tumor or ulceration (with or without stenosis) of the esophagus after irradiation. We analyzed local control factors of these 100 patients to determine the need for further treatment. The cumulative local control rate at five years was 40% in all cases, 37% in 21 cases without any stenosis of the esophagus and 40% in 79 cases with stenosis. The presence of stenosis of the esophagus after irradiation was not a critical factor in predicting final local control. Local recurrence of tumors with findings of Borrmann III or Borrmann IV by the pretreatment esophageal barium study, tumors controlled after a total dose of more than 80 Gy, tumors without low dose rate telecobalt therapy (LDRT; 1 Gy/hour, 5 to 7Gy/day, a total dose of 12 to 15 Gy) as boost therapy, and apparently controlled tumors with a stenotic ratio of 60% or more or with 5 cm or more length of stenosis of the esophagus after irradiation was significantly higher than that of the others (p < 0.05). Multivariate analysis revealed that findings of pretreatment barium study, total dose, with or without LDRT, and length of stenosis of the esophagus after irradiation were significantly important factors in local control. Members of the high risk group of apparently controlled tumors should undertake surgical treatment or further intensive chemotherapy.

Aged↗

A new horizon for the dental hygienist: controlled local delivery of antimicrobials.

All drugs and controlled local delivery systems must be approved by the Food and Drug Administration (FDA) prior to being marketed and used in clinical practice. These systems can only be used in the clinical office setting by the dentist or under his/her supervision. One controlled local antimicrobial delivery system, tetracycline fiber, has been on the market for several years. A second system, chlorhexidine chip, was approved by the FDA in May 1998, and a third system, doxycycline polymer, was approved in September 1998. Local delivery of antimicrobials will significantly change the way periodontitis is treated. Dental hygienists may be key therapists in providing this therapy. This article discusses the science and techniques of the three systems: tetracycline fiber, doxycycline polymer, and chlorhexidine chip. The dental hygienist's role in providing local delivery treatment is stressed. Factors important in selecting the most suitable delivery system are also discussed. This article represents a large portion of the presentation, "The Local Delivery of Antimicrobials in the Treatment of Periodontitis," made at the annual session of the American Dental Hygienists' Association (ADHA) June 27 and 28, 1998.

Anti-Bacterial Agents↗