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PubMedDate not supplied

Chemoradiation followed by surgery: its role in local control in advanced cervical cancer.

The aim of this study was to improve local control and consequently survival, by using chemoradiation followed by surgery. After a median follow-up of 57+ months, 95% CI (9-111) five year overall survival (OS) was 81.8%, 90% and 85.7% in stage Ib2-IIa bulky, IIb and III-IVa, respectively (p = NS). Disease-free survival (DFS) was 81.8% 80% and 71.4% (p = NS) and disease-free survival of local failure (DFSLF) was 95.4%, 80% and 100% (p = NS) for stage Ib2-IIa, bulky, IIb and III-IVa respectively. Distant metastases were present in every group, ranging from 13.6% to 17% in the early bulky and advanced groups respectively. Pathologic findings revealed complete response (CR) (no residual disease or scattered microscopic tumoral foci) in 27/40 (67%), and partial response (PR) in 11/40 (27%). According to the pathologic response, DFS was 92.6% and 50% (p = 0.0029) and DFSLF was 100% and 77.8% (p = 0.0127) in complete and partial response respectively. This therapeutical approach promoted a high rate of pathologic complete response (PCR) PCR as well as of local control in this group at high risk for recurrence.

Adult↗
PubMed1986

Dose response to preoperative irradiation in rectal cancer: implications for local control and complications associated with sphincter sparing surgery and abdominoperineal resection.

Sixty patients with locally advanced adenocarcinoma of the rectum have been treated with preoperative high dose pelvic irradiation at the University of Virginia and Rockingham Memorial Hospital. Fifty-six patients showed no evidence of distant metastases at surgery. A dose response was observed with a 67% incidence of local control with 4000 cGy vs. 91% incidence with 5000 cGy. For the 52 patients who received curative surgery, there has been no local failure alone; 6 of these patients have had local plus distant failure and 16 have had distant failure only. Forty-three percent had anterior resection (AR) and 57% had abdominoperineal resections (APR). The major complication rate was 5% and the minor 14%. No increase in complications or decrease in local control was found between APR and AR. Five-year actuarial survival was 64% for lesions limited to the bowel wall, 59% for node negative lesions with disease extending through the wall, and 23% for node positive patients.

Adenocarcinoma↗
PubMed2004

The impact of gross total resection on local control and survival in high-risk neuroblastoma.

BACKGROUND/PURPOSE: Gross total resection of the primary tumor in treatment of high-risk neuroblastoma remains controversial. Furthermore, there are few reports of the effect of primary tumor resection on local control as opposed to overall survival. The authors reviewed their institutional experience to assess the effect of primary tumor resection on local control and overall survival. METHODS: A total of 141 patients were treated on protocol between November 1, 1979 and June 25, 2002 and are the subject of this report. Gross total resection was assessed by review of operative notes, postoperative computerized axial tomograms, and postoperative meta-iodobenzyl guanidine (MIBG)1 scans when available. RESULTS: The median age was 3.3 years, and all patients were International Neuroblastoma Staging System (INSS) stage 4 with 79% having metastases to cortical bone. The primary site was the adrenal gland in 74%, the central abdominal compartment in 13%, the posterior mediastinum in 7%, and other sites in 6%. Gross total resection was accomplished in 103 (73%) but was more than 90% for the last 3 protocols. Five kidneys were lost overall. The probability of local progression was 50% in unresected patients compared with 10% in patients undergoing gross total resection (P <.01). Overall survival rate in resected patients was 50% compared with 11% in unresected patients (P <.01). CONCLUSIONS: Our data indicate that local control and overall survival rate are correlated with gross total resection of the primary tumor in high-risk neuroblastoma. Gross total resection should be part of the management of stage 4 neuroblastoma in patients greater than 1 year of age.

Abdominal Neoplasms↗
PubMedDate not supplied

Analysing cardiac excitation-contraction coupling with mathematical models of local control.

Cardiac excitation-contraction (E-C) coupling describes the process that links sarcolemmal Ca2+ influx via L-type Ca2+ channels to Ca2+ release from the sarcoplasmic reticulum via ryanodine receptors (RyRs). This process has proven difficult to study experimentally, and complete descriptions of how the cell couples surface membrane and intracellular signal transduction proteins to achieve both stable and sensitive intracellular calcium release are still lacking. Mathematical models provide a framework to test our understanding of how this is achieved. While no single model is yet capable of describing all features of cardiac E-C coupling, models of increasing complexity are revealing unexpected subtlety in the process. In particular, modelling has established a general failure of 'common-pool' models and has emphasized the requirement for 'local control' so that microscopic sub-cellular domains can separate local behaviour from the whole-cell average (common-pool) behaviour. The micro-architecture of the narrow diadic cleft in which the local control takes place is a key factor in determining local Ca2+ dynamics. There is still considerable uncertainty about the number of Ca2+ ions required to open RyRs within the cleft and various gating models have been proposed, many of which are in reasonable agreement with available experimental data. However, not all models exhibit a realistic voltage dependence of E-C coupling gain. Furthermore, it is unclear which model features are essential to producing reasonable gain properties. Thus, despite the success of local-control models in explaining many features of cardiac E-C coupling, more work will be needed to provide a sound theoretical basis of cardiac E-C coupling.

Adaptation, Physiological↗
PubMed2005

Widespread intratumoral virus distribution with fractionated injection enables local control of large human rhabdomyosarcoma xenografts by oncolytic herpes simplex viruses.

Novel methods of local control for sarcomas are needed. We investigated the antitumor effect of two related herpes simplex virus (HSV) mutants, NV1020 and NV1066, on human rhabdomyosracoma cells and xenografts. Cell death correlated with virus replication and apoptosis in cultured cells and tumors. Complete regression was seen in all tumors <250 mm(3) following a single injection, yet only half of tumors >250 mm(3) showed a complete response. Fractionation of the virus dose into five injection sites did not increase transduction efficiency, transgene expression, or virus production, but did yield more widespread intratumoral distribution. Despite the same total dose of virus, improved control of large tumors was seen using fractionated injections as all large tumors (500-700 mm(3)) had durable, complete regression. Our data suggest that oncolytic HSVs may be useful for local control of bulky rhabdomyosarcoma tumors and that fractionated virus administration results in a more widespread virus infection and better tumor control. Therefore, strategies to maximize intratumoral virus distribution at initial delivery should be sought.

Animals↗
PubMed1993

Nasopharyngeal carcinoma: local control by megavoltage irradiation.

This is a retrospective analysis of the long-term local control in 4128 patients with non-disseminated nasopharyngeal carcinoma treated solely by megavoltage irradiation during the years 1976-1985. The T-stage distribution according to Ho's classification was T1 37%, T2 14% and T3 49%. Different fractionation schedules had been employed at different periods, and the median dose to the primary target was equivalent to 65 Gy by time dose fractionation calculation. In 8% (344) of patients the tumour failed to regress completely after the basic course, but 89% (148/167) of those suitable for salvage with additional irradiation eventually attained complete local remission. The cumulative incidence of local failure was 24% (5% persistence, 19% recurrence). The 10-year actuarial local failure-free survival was 67%. While patients with T2 and T3a tumours achieved local control comparable to T1, those with T3c-d had the poorest control (with highest incidence of persistence and advanced recurrence). T-stage adjusted analyses suggested a significant trend of dose-response: the odds ratios for local failure were 1.16 and 1.86, respectively, when patients given 60-63 Gy and 55-59 Gy were compared with those given 64 Gy or above (p value = 0.0018). Patients treated during 1981-1985 achieved higher local failure-free survival than those treated during 1976-1980 (75% versus 70% at 5 years, p value = 0.0013). The possible attributes are studied, and ways for future optimization of treatment discussed.

Adolescent↗
PubMed1989

Local control in rectal cancer. A clinical review and meta-analysis.

We reviewed the factors influencing local control of potentially curable rectal cancer in 106 patients. There was improvement in stage-adjusted local control associated with increasing use of adjuvant radiation therapy. A meta-analysis of the English-language literature through 1988 also supported the effectiveness of adjuvant radiation therapy in all but the lowest-risk patients. No effect on survival was identified in either analysis, but a reduction of up to 40% in local recurrence rates may be achieved with doses of 3000 cGy or more.

Humans↗
PubMed1977

Hypoxic cell radiosensitizers and local control by X-ray of a transplanted tumour in mice.

Tumour experiments including local control after X-irradiation have been performed, using a new technique that eliminates the need for anaesthetics in restraining the animals. This system has been used to investigate the degree of sensitization that can be achieved with ICRF 159 and 4 strongly electron-affinic radiosensitizers, nifurpipone dihydrochloride, metronidazole, Ro-11-3696 and Ro-07-0582. No significant enhancement of the radiation effect was observed with ICRF 159. Significant sensitization was achieved by all 4 nitro-heterocyclic compoinds, Ro-07-0582 being the most effective, metronidazole and Ro-11-3696 the next, and nifurpipone dihydrochloride the least effective. For Ro-07-0582 and metronidazole, several concentrations were investigated, and the interval between injection with Ro-07-0582 and irradiation was varied: an interval of 30 min gave more sensitization than an interval of 90 min. The results from the local control experiments using Ro-07-0582 have been compared with those obtained from regrowth delay experiments. The radiosensitization obtained by the Ro-07-0582 increased with the X-ray dose above 25 gray. Both metronidazole and Ro-07-0582 gave significant enhancement effect at serum concentrations which can be achieved in man.

Animals↗
PubMed1994

Influence of tumoral, radiobiological, and general factors on local control and survival of a series of 361 tumors of the velotonsillar area treated by exclusive irradiation (external beam irradiation+brachytherapy or brachytherapy alone)

PURPOSE: To evaluate statistically the factors influencing the therapeutic results. METHODS AND MATERIALS: A statistical study was carried out concerning 361 patients treated from 1977 to 1991 for velotonsillar carcinoma. They received either brachytherapy alone (18) or a combination of external beam irradiation and brachytherapy (343 patients) using an afterloading iridium technique in plastic tubes. The distribution of patients according to the localization was: 128 tonsils, 134 soft palates, 9 posterior pillars, 63 anterior pillars, and 27 glossotonsillar sulcus. The patients were staged as follows: 90 T1, 141 T2, 119 T3, 2 T4, 9 Tx with 230 N0, 93 N1, 9 N2, 20 N3, and 9 Nx. RESULTS: The results at 5 and 10 years show: local control 80% and 74%, locoregional control 75% and 70%, overall survival 53% and 27%, specific survival 63% and 52%, respectively. The univariate study shows at 5 years a better local control for T1T2 (87%) compared with T3 (67%) with p = 0.00004. The locoregional control is better for N0 (80%) than for N+ (55%) with p = 0.002. This is the same for the overall survival (59% vs. 42%, p = 0.002). Tumors with an extension to the mobile tongue or the base have a poor prognosis (p < 0.002). The radiobiological factors show less recurrences if the total duration of the treatment is < 55 days, the number of days between External Beam Irradiation and brachytherapy is < 20. The security margin seems important also. CONCLUSIONS: For the combination external irradiation and brachytherapy, the multivariate study for local control shows that ony T, localization, and the total duration of treatment are significant. For complications, classified into four grades, only the dose rate is significant.

Adult↗
PubMed2000

Surgery for T4 breast carcinoma: implications for local control.

Despite increasing public awareness and widespread availability of mammography, many patients will present with locally advanced breast cancers. The role of surgery remains controversial. Between 1993 and 1998, 47 of 393 (11.9%) breast cancer patients presented with T4 (inflammatory or locally advanced) carcinoma. We reviewed multimodality management, clinical response to neoadjuvant therapy, perioperative course and complications, and local control. Forty-six women and one man were diagnosed with clinical T4 breast cancer. There were 24 white and 23 African-American patients. Mean age at presentation was 54.5 (range, 31-88) years. Twenty-three patients had clinical metastases to axillary nodes, and five had distant metastases at the time of diagnosis. For these women, intent was for personal hygiene and control of pain. Neoadjuvant chemotherapy was given for 34 of 47 (72%) with 25 of 34 (73.5%) having partial or complete clinical response. There was no response or progression of disease in 9 of 34(26.5%). Forty-six patients underwent radical or modified radical mastectomy, whereas a single patient underwent breast conservation treatment. Twelve required tissue transfer for wound coverage. Although eight developed minor wound complications (cellulitis/flap separation), there were no major wound complications. Pathologically negative margins were achieved in all but one patient. To date, five women have developed local recurrence in either the chest wall (three) or axilla (two). Average time to local recurrence was 7.8 months. There is no evidence of local failure in the remaining 87 per cent. Locally advanced breast cancer is a common occurrence in certain populations. Multimodality management remains the standard of care. Surgical resection may allow for successful local control and, in certain situations, long-term cure.

Adult↗
PubMedDate not supplied

Role of the endothelium in controlling local blood flow.

During this last decade it has been widely recognized that the vascular endothelium reacts to mechanical force as well as to various neurohumoral mediators by releasing vasodilator and/or vasoconstrictor substances, and thus contributes to the relaxation of local blood vessels and the control of local circulation. In addition, substances produced and released by endothelial cells play a major role in controlling platelet-endothelium interaction and platelet aggregation. The endothelium may contribute to the local control of vascular tone by secreting prostacyclin, endothelium-derived relaxing factor(s) (EDRF) or endothelium derived contracting factor(s) (EDCF). Prostacyclin, a major metabolite of the cyclo-oxygenase pathway in the vascular endothelium and the subject of intense studies since its discovery in 1976, has been reviewed many times and will therefore not be discussed in this report. We will focus on other recently described endothelium-dependent vasoactive mediators, particularly EDRF and EDCF.

Animals↗
PubMed1986

Impact of improved local control on survival in patients with soft tissue sarcoma.

An estimate has been made of the gain in survival if the local failure rate for sarcoma of soft tissue was reduced to zero by the application of new treatment methods. The assumption is that the loss, due to distant metastasis and intercurrent disease among patients who achieve local control by the current treatment, would be the same among new local controls. For patients with stage M0 disease at diagnosis (all sites, all histological types), the current local failure rate is approximately 30%. By eliminating these failures, the overall survival rate would be expected to increase by 10-20 percentage points.

Combined Modality Therapy↗
PubMed1992

Does preoperative radiation therapy enhance the probability of local control and survival in high-risk distal rectal cancer?

One hundred forty-eight patients were treated with preoperative radiation therapy and surgery for resectable rectal adenocarcinoma at the University of Florida between 1975 and 1986. All patients had at least 5 years' follow-up; no patient was lost to follow-up. Three treatment protocols were used over the study period: 1975 to 1978, 3500 cGy in 20 fractions; 1979 to 1983, 4000 to 5000 cGy at 180 cGy per fraction; and 1984 to 1986, 3000 cGy in 10 fractions. The change was made to 3000 cGy in 10 fractions to reduce the inconvenience and expense associated with preoperative radiation therapy without sacrificing any improvement in local control or complication rates. There were no significant differences in the rates of local control, absolute survival, cause-specific survival, or complications between the three preoperative radiation therapy protocols. The results were compared for the 132 patients who underwent complete resection after preoperative radiation therapy and a series of 135 patients who underwent a complete resection alone for adenocarcinoma of the rectum at the University of Florida between 1959 and 1976. The results at 5 years, calculated by the product-limit method, for preoperative radiation therapy and surgery compared with surgery alone, respectively, were as follows: for local recurrence-free survival, 96% and 67%; for absolute survival, 66% and 40%; and for cause-specific survival, 77% and 50%. All of these differences are significant (p = 0.0001 or less). A subset of 56 patients with locally advanced lesions, based on tethering or circumferential involvement of the rectal lumen, treated with preoperative radiation therapy and surgery were compared with patients treated with surgery alone for stage B2 and C cancers. There was a significant improvement in local control and survival rates in the group irradiated before operation. There was no apparent increase in the incidence of postoperative complications in the patients irradiated before operation.

Adenocarcinoma↗
PubMed1996

Does neck stage predict local control after irradiation for head and neck cancer?

The impact of neck stage (N stage) on local control after treatment for head and neck cancer is controversial. This article reviews the pertinent literature. Based on this review, the authors conclude that although N stage may be inversely related to local control, the relationship is relatively weak. Hence, current data are insufficient to justify altering treatment of the primary lesion based solely on N stage.

Head and Neck Neoplasms↗
PubMed1991

Radical surgery and postoperative split-course radiotherapy in squamous cell carcinoma of the mobile tongue: factors influencing local control and the time to recurrence.

During 1981-1988 63 patients with squamous cell carcinoma of the oral tongue (27 females and 36 males) were treated with radical surgery and postoperative split-course radiotherapy. The 3-week rest period was compensated with a 10% increase in the total radiation dose to 66 Gy. The local control rate was 76% in stage I, 71% in stage II, 45% in stage III and 0% in stage IV. Failures were observed in 25 (40%) patients, and 8 patients died of intercurrent diseases. For further analysis the material was stratified in three groups according to the time interval between surgery and postoperative radiotherapy: less than 6 weeks, 6-8 weeks and greater than 8 weeks. The local control rate in the three strata were 75, 57 and 44%, and the 5-year actuarial survival 61, 46 and 30%, respectively. In the logistic regression analysis and the proportional hazard's regression analysis the histologic grade of the primary tumour and the time interval between surgery and the start of radiotherapy were the most important factors influencing respectively local control and time to recurrence. However, it appeared that the lengthening of the time interval was often caused by factors or events which directly can influence the prognosis, such as surgical complications, infections and poor general condition. When cases with such special causes for lengthening of the interval were excluded, the effect of the time interval nearly completely disappeared. It would seem that a final evaluation of the effect of the time interval requires a prospective randomized trial. The same may well hold true for reliable evaluation of the influence of overall treatment time.

Carcinoma, Squamous Cell↗
PubMed1993

Temperature differentials between treatment and pretreatment temperatures correlate with local control following radiotherapy and hyperthermia.

PURPOSE: To evaluate the influence of pretreatment tumor temperatures and the temperature differential between treatment and pretreatment temperatures on local tumor control in patients who underwent combined radiation therapy and hyperthermia. METHODS AND MATERIALS: Mapped intratumoral temperatures were measured immediately prior to and during hyperthermia in 138 hyperthermia fields among 59 patients with nodular (60 fields) or diffuse (78 fields) superficially-located tumors. In the nodular subgroup there were 40 fields with adenocarcinomas (31 breast, two prostate, seven other primary sites), six melanomas, nine squamous cell carcinomas, and five other histologies. The fields with diffuse tumor involvement consisted of 77 adenocarcinomas (67 breast, 10 other) and one melanoma. The maximum, minimum, and average temperatures were determined for both the pretreatment (pTmax, pTmin, pTave) and treatment (Tmax, Tmin, Tave) distributions and the differences, Dm = Tmin-pTmax, and Da = Tmin-pTave, computed. These quantities were averaged over treatments to produce the corresponding mean quantities for each hyperthermia field. Univariate and multivariate analyses were performed to determine treatment and pretreatment parameters which best correlated with the duration of local control. RESULTS: Pretreatment tumor temperatures were significantly lower than the oral temperatures with mean pTmax, mean pTmin, and mean pTave of 36.2 degrees C, 34.2 degrees C, and 35.4 degrees C, respectively. For the adenocarcinomas with diffuse involvement within the hyperthermia field, the covariates best correlating with local control duration on univariate analysis were concurrent radiation dose (p = 0.0026), Dm (p = 0.009), pTmax (p = 0.012) and Da (p = 0.036). Lower pTmax and larger Dm and Da were predictive for longer local control. In multivariate analyses, all thermal parameters lost power, however, the best model included Dm which was significant at the p = 0.040 level. For the nodular subgroup, nonthermal parameters and dichotomized thermal parameters were of prognostic significance for local control. CONCLUSION: For fields diffusely involved with adenocarcinoma significant correlations with duration of local control have been demonstrated both for a) low pretreatment temperatures and b) large differentials between treatment and pretreatment intratumoral temperatures. These correlations were also found in a dichotomized description for fields with nodular tumors. The results support the concept that pretreatment hypothermic conditions can lead to an increase in thermal sensitization and may help explain the excellent clinical results noted in the treatment of superficial tumors with radiation and hyperthermia. Further exploitation of this approach by planned cooling of superficially-located recurrent tumors prior to hyperthermia treatment warrants investigation.

Body Temperature↗
PubMed2006

Influence of number of CAG repeats on local control in the RTOG 86-10 protocol.

OBJECTIVES: The number of CAG repeats on the androgen receptor (AR) gene is inversely proportional to transcriptional activity. The purpose of this study was to determine if short-term androgen deprivation therapy (RT + HT) can improve outcome in patients with tumors with short CAG repeats (<19). MATERIALS AND METHODS: Prostate cancer patients were randomized to receive either radiotherapy (RT) alone or (RT + HT) in the RTOG 86-10 study. CAG repeats were measured in 94 tumor specimens (21%; test cohort) of the 456 (parent cohort) analyzable cases. AR flow cytometry measurements were done on 13 patients. The effect on local failure (LF), distant metastases (DM), prostate cancer survival (PSS), and overall survival (OS) was studied. RESULTS: Pretreatment characteristics and assigned treatment arm were not significantly different between the parent and test groups except for a significantly higher risk of death (P = 0.049) in the test group. The median CAG repeat was 19. There were no significant differences in stage, or Gleason score between high (19 or greater) and low CAG (<19) patients within each treatment group. Number of CAG repeats alone did not significantly influence LF, DM, PSS, and OS. However, when the CAG repeat outcome was studied in conjunction with androgen deprivation therapy, patients with CAG <19 who received H + RT had improved local control as compared with patients who received RT alone (P = 0.026, 5-year rates 4.6% versus 36.4%) and improved local control over patients with CAG > or =19 that received H + RT (P = 0.028). CONCLUSIONS: Patients with short CAG repeats show a local control benefit with short-term androgen deprivation therapy, but no improvement in survival.

Androgen Antagonists↗
PubMed1988

T1-T2 squamous cell carcinoma of the glottic larynx treated with radiation therapy: relationship of dose-fractionation factors to local control and complications.

This is an analysis of 304 patients with invasive, previously untreated T1-T2 squamous cell carcinoma of the glottic larynx treated with radiation therapy at the University of Florida between October 1964 and December 1984. All patients had a minimum 2-year follow-up and 82% had at least 5 years of follow-up. Patients were excluded from the analysis of local control if they died within 2 years of treatment with the primary site continuously disease-free; all patients were included in the analysis of treatment complications. Patients were staged according to the 1983 AJCC system. Stage T2 was subdivided into 2 groups as follows: T2a (normal mobility) and T2b (decreased mobility). The rates of local control with radiation therapy were as follows: T1, 159/171 (93%); T2a, 50/65 (77%); and T2b, 31/43 (72%). Patients were further divided into subsets based on T stage and the surgical procedure that would have been required to resect the lesion. Local control was noted to improve with higher doses and dose per fraction in 4 of 7 subsets. In 2 of 3 subsets where a dose-fractionation relationship was not observed, there were no local recurrences in 1 subset and only 2 local recurrences in the other. The overall incidence of serious complications was 5/304 (1.6%) and was associated with T stage and with increasing total dose and dose per fraction.

Carcinoma, Squamous Cell↗