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Evaluation of functional outcome and local control after radiotherapy for metastatic spinal cord compression in patients with prostate cancer.

PURPOSE: Patients with prostate cancer with metastatic spinal cord compression have better survival prognosis than other patients with MSCC and may live long enough to develop a local recurrence of MSCC. This study investigates prognostic factors and radiation schedules for functional outcome and local control of MSCC after radiotherapy in patients with prostate cancer. MATERIALS AND METHODS: A total of 281 patients irradiated between January 1992 and December 2003 were included. Potential prognostic factors were investigated including age, performance status, number of involved vertebra, pretreatment ambulatory status, time of developing motor deficits before RT and radiation schedule--short course RT (1x8/5x4 Gy) vs long course RT (10x3/15x2.5/20x2 Gy). RESULTS: Overall response to RT was 86% (33% improvement of motor function, 53% no further progression). Of the nonambulatory patients 33% regained the ability to walk. On multivariate analysis functional outcome was significantly affected by the time of developing motor deficits before RT (more than 14 days better than 8 to 14 days and 1 to 7 days, p <0.001) and number of involved vertebrae (1 to 2 better than 3 or more, p = 0.013), but not by the radiation schedule (p = 0.859). The 2-year local control of MSCC was 84% depending on the radiation schedule (better after long course RT, p = 0.001). CONCLUSIONS: Functional outcome after RT was significantly influenced by the time of developing motor deficits before RT and number of involved vertebra. Local control was significantly better after application of long course RT. Patients with a poor expected survival could be treated with short course RT, because a short treatment time means less discomfort for the patient. For patients with good survival prognosis, long course RT should be applied to achieve better local control.

Aged↗

Local control with multimodality therapy for stage 4 neuroblastoma.

PURPOSE: To evaluate the efficacy of 21 Gy hyperfractionated radiotherapy for local control in conjunction with surgery and intensive systemic therapy for patients with Stage 4 neuroblastoma. METHODS AND MATERIALS: After achieving a partial or complete remission, 47 children, ages 1-10 years, with Stage 4 neuroblastoma were treated on four consecutive institutional protocols (N4-N7) with dose-intensive multi-agent chemotherapy, maximal surgical debulking, and hyperfractionated radiotherapy (1.5 Gy twice a day to 21 Gy). Radiotherapy fields encompassed the initial tumor volume and regional lymph nodes plus a 3-cm margin. This was followed by consolidation with either autologous bone marrow transplantation (N4 and N5) or immunotherapy (N6 and N7). RESULTS: Forty-five of 47 patients had a complete response to surgery and chemotherapy prior to radiotherapy. Five-year actuarial rates of local control, progression-free survival, and overall survival were 84%, 40%, and 45%, respectively. Among 26 patients who relapsed, 1 failed only at the primary site, 22 developed distant metastases exclusively, and 3 had both local and distant failures. There were no acute complications of radiotherapy. CONCLUSION: Hyperfractionated radiotherapy to 21 Gy, in conjunction with dose-intensive systemic therapy and aggressive surgical resection, is well tolerated and is associated with durable local control for most patients with Stage 4 neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols↗

[The effects of surgical margins on local control and survival in extremity soft tissue sarcomas].

OBJECTIVES: We evaluated the effects of surgical margins and other prognostic factors on local control and survival in extremity soft tissue sarcomas. METHODS: The study included 40 patients (34 males, 6 females; mean age 45 years; range 13 to 77 years) who underwent treatment for extremity soft tissue sarcomas. Of these, 14 patients presented with recurrences following treatment elsewhere. Preoperatively, nine patients and eight patients; postoperatively, 35 patients and 25 patients received radiotherapy and chemotherapy, respectively. Limb-salvaging surgery was performed in 35 patients (87.5%), of whom 28 patients (70%) received an extended resection, and seven patients received a marginal resection. Five patients (12.5%) required amputation. Negative surgical margins were achieved in 34 patients (85%), while six patients (15%) had positive surgical margins. The mean follow-up period was 58 months (range 13 to 124 months). RESULTS: Five patients (12.5%) developed local recurrences following marginal resection (n=4), and amputation. No local recurrences were seen in patients receiving an extended resection or in those having negative surgical margins. Five-year survival rates were 51% and 49% in patients whose initial diagnoses were made in our department and elsewhere, respectively. Significant correlations were found between extended resection (p=0.0001) and negative surgical margins (p=0.0001) and local control; and between tumor grade and survival (p=0.002). Positive surgical margins and local recurrences did not decrease survival. CONCLUSION: Achievement of negative surgical margins promotes local control in extremity soft tissue sarcomas. A careful preoperative planning and utilization of neoadjuvant therapies highly increase the possibility of negative surgical margins.

Adolescent↗

Effective local control and long-term survival in patients with T4 locally advanced breast cancer treated with breast conservation therapy.

BACKGROUND: The presence of skin involvement has been accepted as a relative contraindication to breast preservation because it is believed to be associated with an increased local failure rate. This study was conducted to assess the outcome of a carefully selected group of patients who presented with breast cancer involving the skin and who had breast conservation therapy (BCT) following neoadjuvant chemotherapy. METHODS: Between 1987 and 1999, 33 patients with stage IIIB or IIIC breast cancer completed treatment consisting of four cycles of neoadjuvant chemotherapy, lumpectomy, radiation therapy, and consolidative chemotherapy. Clinicopathologic factors were analyzed and patients were followed for locoregional and distant recurrence. RESULTS: Initial median tumor size was 7 cm. All patients had skin involvement, defined as erythema, skin edema, direct skin invasion, ulceration, or peau d'orange. Following chemotherapy, median pathologic tumor size was 2 cm. Complete resolution of skin changes occurred in 29 patients (88%). At median follow-up time of 91 months in surviving patients, 26 patients (79%) were alive without evidence of disease. The 5-year, disease-free survival rate was 70%, and the 5-year overall survival rate was 78%. The actuarial ipsilateral breast cancer recurrence rate was 6% at 5 years. CONCLUSIONS: Patients who present with T4 breast cancer who experience tumor shrinkage and resolution of skin changes with neoadjuvant chemotherapy represent a select group of patients who can have BCT. These patients have favorable rates of long-term local control and survival. Mastectomy is not mandatory for all patients with breast cancer who present with skin involvement.

Adult↗

Alternative approaches to evaluating the impact of local control on survival.

An important aspect of evaluating treatments aimed at local tumor control is to assess the effect of local control on survival. A common approach to this problem is to compare all patients who have failed locally with those who have not using a logrank test. However, this method of analysis does not take into account the effect of time on a patient's local disease status. Since patients in the local failure group must survive long enough to fail, this group may be biased in favor of longer survival times. The Mantel-Byar extension of the logrank test avoids this source of bias by utilizing the data on time to local failure in defining the local control and local failure groups. In this paper, the application of this technique is illustrated using data from recurrent breast cancer patients and contrasted with the results obtained using the standard logrank test.

Breast Neoplasms↗

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.

Carcinoma, Squamous Cell↗

Comparison of injection pain, heart rate increase, and postinjection pain of articaine and lidocaine in a primary intraligamentary injection administered with a computer-controlled local anesthetic delivery system.

The purpose of this prospective, randomized, double-blind study was to compare the pain of injection, heart rate increase, and postinjection pain of the intraligamentary injection of 4% articaine with 1:100,000 epinephrine and 2% lidocaine with 1:100,000 epinephrine administered with a computer-controlled local anesthetic delivery system. Using a crossover design, intraligamentary injections of 1.4 mL of 4% articaine with 1:100,000 epinephrine and 1.4 mL of 2% lidocaine with 1:100,000 epinephrine were randomly administered on the mesial and distal aspects of the mandibular first molar with a computer-controlled local anesthetic delivery system in a double-blind manner at 2 separate appointments to 51 subjects. The results demonstrated the incidence of moderate pain was 14%-27% with needle insertion, with 0%-4% reporting severe pain. For solution deposition, moderate pain was reported 8%-18% of the time, with no reports of severe pain. There were no significant differences between the articaine and lidocaine solutions. Regarding heart rate changes, neither anesthetic solution resulted in a significant increase in heart rate over baseline readings. On day 1 postinjection, there was a 31% incidence of moderate/severe pain with the articaine solution and 20% incidence of moderate/severe pain with the lidocaine solution. The moderate/severe pain ratings decreased over the next 2 days. There were no significant differences between the articaine and lidocaine solutions. We concluded that the intraligamentary injection of 4% articaine with 1:100,000 epinephrine was similar to 2% lidocaine with 1:100,000 epinephrine for injection pain and postinjection pain in the mandibular first molar when administered with a computer-controlled local anesthetic delivery system. For both anesthetic solutions, heart rate did not significantly increase with the intraligamentary injection using the computer-controlled local anesthetic system.

Adult↗

Local control model of excitation-contraction coupling in skeletal muscle.

This is a quantitative model of control of Ca release from the sarcoplasmic reticulum in skeletal muscle, based on dual control of release channels (ryanodine receptors), primarily by voltage, secondarily by Ca (Ríos, E., and G. Pizarro. 1988. 3:223-227). Channels are positioned in a double row array of between 10 and 60 channels, where exactly half face voltage sensors (dihydropyridine receptors) in the transverse (t) tubule membrane (Block, B.A., T. Imagawa, K.P. Campbell, and C. Franzini-Armstrong. 1988. 107:2587-2600). We calculate the flux of Ca release upon different patterns of pulsed t-tubule depolarization by explicit stochastic simulation of the states of all channels in the array. Channels are initially opened by voltage sensors, according to an allosteric prescription (Ríos, E., M. Karhanek, J. Ma, A. González. 1993. 102:449-482). Ca permeating the open channels, diffusing in the junctional gap space, and interacting with fixed and mobile buffers produces defined and changing distributions of Ca concentration. These concentrations interact with activating and inactivating channel sites to determine the propagation of activation and inactivation within the array. The model satisfactorily simulates several whole-cell observations, including kinetics and voltage dependence of release flux, the "paradox of control," whereby Ca-activated release remains under voltage control, and, most surprisingly, the "quantal" aspects of activation and inactivation (Pizarro, G., N. Shirokova, A. Tsugorka, and E. Ríos. 1997. 501:289-303). Additionally, the model produces discrete events of activation that resemble Ca sparks (Cheng, H., M.B. Cannell, and W.J. Lederer. 1993. 262:740-744). All these properties result from the intersection of stochastic channel properties, control by local Ca, and, most importantly, the one dimensional geometry of the array and its mesoscopic scale. Our calculations support the concept that the release channels associated with one face of one junctional t-tubule segment, with its voltage sensor, constitute a functional unit, termed the "couplon." This unit is fundamental: the whole cell behavior can be synthesized as that of a set of couplons, rather than a set of independent channels.

Animals↗

Local control of blood pressure by purines.

Dual control of local blood flow by purines is described: adenosine 5'-triphosphate (ATP) released as a cotransmitter with noradrenaline from perivascular sympathetic nerves acts on P2X-purinoceptors on smooth muscle cells to produce vasoconstriction; ATP released from endothelial cells during hypoxia (and ADP released from aggregating platelets) acts on P2Y-purinoceptors on endothelial cells which results in production of endothelium-derived relaxing factor and subsequent vasodilatation. It is suggested that the endothelial-mediated vasodilatation is a pathophysiological mechanism to protect the host tissue (e.g. brain or heart) from damage produced by hypoxia following ischaemia. The ATP released from the endothelial cells is rapidly broken down to adenosine which augments this protective mechanism by acting directly on P1-purinoceptors on vascular smooth muscle to produce a longer lasting component of vasodilatation and on perivascular sympathetic nerve terminals to inhibit release of excitatory neurotransmitters. The possibility that impairment of normal endothelial-mediated responses in atherosclerosis and hypertension can lead to local vasospasm is considered.

Animals↗

Radical surgery and postoperative split-course radiotherapy in squamous cell carcinoma of the head and neck--factors influencing local control and survival.

During the period 1970-1989, 256 patients with squamous cell carcinoma of the head and neck were treated with radical surgery and postoperative split-course radiotherapy. The 3-week rest period was compensated by a 10% increase in the total radiation dose to 66 Gy. The 5-year actuarial local control rate was 66% in tonsillar, 60% in mobile tongue, 64% in floor of the mouth, 51% in lower gingiva, 63% in laryngeal, and 35% in hypopharyngeal cancer. Failures were observed in 102 patients (40%) and 51 (20%) died of intercurrent diseases. Except in mobile tongue cancer, the results in the logistic regression analyses showed that T- and N-category and pretreatment Karnofsky index had the strongest association with local control, whereas in Cox's proportional hazard's regression analyses T-category and pretreatment Karnofsky had the strongest association with survival. In mobile tongue cancer, the histologic grade and the time interval between surgery and radiotherapy had the strongest association with local control and survival respectively. However, the lengthening of the time interval was often caused by factors or events which could have influenced the prognosis. On the basis of both univariate and multivariate analyses, when the tumour resection margins were free, a time interval of less than 3 months, the overall treatment time and the duration of the split of radiotherapy, became less important for local control and survival when doses of 65 Gy were given by fraction of 2 Gy or greater.

Adolescent↗

Primary tumor volume of nasopharyngeal carcinoma: prognostic significance for local control.

PURPOSE: To study the prognostic significance of primary tumor volume on local control of nasopharyngeal carcinoma. METHODS AND MATERIALS: Between 1998 and 2001, 308 consecutive patients with nasopharyngeal carcinoma treated with radical intent were staged with MRI. On the basis of the extent of tumor infiltration outlined by a diagnostic radiologist, the gross tumor volume of the primary and involved retropharyngeal nodes (GTV-P) was delineated by a radiation oncologist for three-dimensional conformal radiotherapy to the nasopharyngeal region using the Helax-TMS Planning System. All patients were treated with 2 Gy daily to a total dose of 70 Gy in 6-7 weeks. Additionally, chemotherapy was given to 128 patients (42%). RESULTS: The median GTV-P for the whole series was 22 cm(3) (range, 1.4-218 cm(3)). Although the GTV-P varied substantially within each T stage, the overall correlation between these two parameters was strongly significant (p <0.01), with the median GTV-P 2.7 cm(3) for T1, 13.2 cm(3) for T2, 28.1 cm(3) for T3, and 65.5 cm(3) for T4. With a median follow-up of 1.9 years (range, 0.1-3.9 years), the 3-year local failure-free rate was 87%. The 3-year local failure-free rate was 97% for patients with a GTV-P <15 cm(3) compared with 82% for those with a GTV-P > or =15 cm(3) (p <0.01). On multivariate analysis (with T stage as a covariate), GTV-P remained an independent prognostic factor for the local failure-free rate (hazard ratio, 1.01; 95% confidence interval, 1.00-1.02; p <0.01). CONCLUSION: Our data suggested that GTV-P is a strongly significant factor for predicting local control of nasopharyngeal carcinoma. The risk of local failure was estimated to increase by 1% for every 1 cm(3) increase in primary tumor volume.

Adolescent↗

The effect of waiting time on local control and survival in head and neck carcinoma patients treated with radiotherapy.

PURPOSE: To determine the influence of waiting time for radiotherapy on local control and survival in a cohort of patients with head and neck carcinoma of different locations and stages treated with radiotherapy. MATERIAL AND METHODS: Retrospective study of 797 patients with squamous cell carcinoma located in the oral cavity, pharynx or larynx, treated with radiotherapy, and with a minimum follow-up of 3 years. Local recurrence and survival were analyzed in function of the waiting time, defined as the interval between date of histologic diagnosis and date of radiotherapy. A univariate and multivariate analysis was carried out. RESULTS: Median waiting time to radiotherapy was 44 days (25 and 75% quartiles: 33 and 60 days). There were significant differences in the waiting time period in relation to the primary location and the local extension of the tumor. Both univariate and multivariate analysis showed that waiting time had no significant impact either on local control or survival. CONCLUSION: Within the range of the waiting time observed in our study, delay in the initiation of radiotherapy did not affect local control or survival in patients with head and neck carcinoma.

Aged↗

Effect of age and radiation dose on local control after breast conserving treatment: EORTC trial 22881-10882.

PURPOSE: To determine whether the effect of an additional "boost" radiation after breast conservative therapy (BCT) on local control depends on age and evaluate the impact of a treatment policy with a threshold for age. PATIENTS AND METHODS: We used data from EORTC 22881-10882 trial, with median follow-up of 77.4 months. Patients receiving BCT and 50Gy whole breast irradiation were randomized to no boost and 16Gy boost (N=5318). RESULTS: In univariate analysis, a boost reduced local failure by a factor of 2 (P<0.0001). Multivariate analysis showed local control increased with age (P=0.0003). There was no evidence that the relative effect of a boost on local control depends on age (P=0.97) However in younger patients the 5-year local failure was higher, therefore the absolute reduction was greater. If the threshold-age for boost treatment were set at 40 years, 8.4% of the study population would receive a boost, resulting in a 5-year local failure of 6.1% in the study population. Changing the threshold-age to 60 years, 67% of the study population would receive a boost and the 5-year local failure would be reduced to 4.4%. CONCLUSIONS: In younger patients a boost dose resulted in a greater absolute reduction of local failure. The relative risk reduction was however similar for all ages. Applying a treatment policy with a threshold-age of 60 would result in 0.6% increase in local failure in the total study population, while sparing the boost to 1/3 of the patients.

Adult↗

Effect of dose rate on local control and complications in the reirradiation of head and neck tumors with interstitial iridium-192.

Interstitial Iridium-192 was used as the sole treatment for 23 previously irradiated patients with recurrent or second primary malignancy in the head and neck region. Doses used in initial external beam treatment ranged from 50.0 to 72.0 Gy, in daily fractions of 180 to 200 cGy. Retreatment with interstitial implant using the Quimby system delivered total doses between 38.5 and 60 Gy, with hourly dose rates of 30 to 66 cGy. Local control in the implanted volume was seen in 21 of 23 patients at 5 to 34 months post-implant (median 10 months). Dose rate (hourly dose delivered at 0.5 cm beyond the periphery of the implanted tumor volume) did not affect local control, but did have a significant impact on severe complications (soft tissue necrosis and fistulae; p = 0.26). No effect on either local control or complication rate was found for volume of implant, initial external beam radiation dose, time to recurrence, or anatomic site of treatment. These findings suggest that interstitial irradiation is effective treatment for head and neck cancers in previously irradiated sites. Dose rates as low as 32 cGy/hr provided adequate local control, with few long-term complications to date; doses above 42 cGy/hr may be associated with severe and even fatal complications.

Adult↗

Concurrent paclitaxel-cisplatin and twice-a-day irradiation in stage IIIA and IIIB NSCLC shows improvement in local control and survival with acceptable hematologic toxicity.

Non-small-cell lung cancer (NSCLC) has one of the highest death rates among the various forms of cancer. In attempts to improve on this unsatisfactory outcome, different radiation schedules and chemo-therapy agents have been examined in phase II or III studies. These have led to modest improvements in local control and survival, but combined therapies are associated with substantial hematologic toxicity. In this phase II study, 80 consecutive stage IIIA or IIIB NSCLC patients were treated with concomitant chemotherapy and twice-a-day irradiation in a total dose of 60 Gy in 1.5 Gy fractions. Patients scheduled for surgery received 45 Gy only. Paclitaxel (30 mg/m 2 ) on days 1-4 and cisplatin (100 mg/m 2 ) on day 5 were administered in the first and fourth weeks of treatment. Granulocyte colony stimulating factor (30 ng/m 2 ) was given on days 10-15. The local control, the 1- and 2-year survival rates and the occurrence of acute hematologic toxicity in the non-surgically treated patients were examined. Fifty-two patients were treated without and 28 with surgery. Among the non-surgically treated cases, 43 were evaluable for response and 47 for acute toxicity during a median follow-up of 22 months. The rate of local control was 65% (28/43), and the 1- and 2-year survival rates proved to be 68% and 48%, respectively, with a median survival of 28 months. Severe acute grade 3-4 toxicities included grade 4 leukopenia in 6 cases (13%), grade 3 leukopenia in 4 cases (9%), grade 3 esophagitis in 3 cases (6%) and grade 3 anemia in 3 cases (6%). Our results and the relevant data from the literature support the application of twice-a-day irradiation with concomitant chemotherapy in stage IIIA and IIIB NSCLC. Local control and survival were improved relative to once-a-day irradiation with sequential or concomitant chemotherapy.

Adult↗

Local control of carcinoma of the tonsil by radiation therapy: an analysis of patterns of fractionation in nine institutions.

PURPOSE: To investigate the importance to outcome of treatment for squamous cell carcinomas of the tonsillar fossa, of dose per fraction, overall treatment duration, and total dose. METHODS AND MATERIALS: A collaborative retrospective study was undertaken in nine centers that used widely different dose-fractionation patterns for external beam radiation therapy. RESULTS: There were 676 eligible cases treated only with photon beams during the years 1976-1985. The probability of local control (of the tonsillar fossa primary) was influenced by both T-stage and N-stage. Significant treatment parameters were total dose and overall treatment duration, but not dose per fraction. Over the range of about 40 to 90% and for a constant overall treatment duration, local tumor control probability increased by nearly 2% for each 1 Gy increase in total dose. For a constant total dose there was a decrease in the probability of local control associated with prolongation of overall treatment duration, presumed to result from accelerated regrowth of surviving tumor clonogens during the course of treatment. If it is assumed that accelerated regrowth occurred at a constant rate and began within 9 days of the start of treatment, an average of 0.53 Gy extra dose per day's extension of treatment would be required to maintain a constant probability of local control. Correspondingly, the probability of local control from a constant dose would be lowered by an average of at least 1% for each day's extension of treatment duration. However, the data are slightly more consistent with an average delay of as long as 30 days before onset of accelerated repopulation, with a consequent increase to an average of 0.73 Gy per day for the value of the compensatory dose. The alpha/beta ratio for this tumor is high enough that the effect of fraction size on the probability of local control can be ignored; a precise estimate is not possible because the best value for beta was close to zero. After accounting for the significant variables studied (treatment time, T-stage, N-stage), the dose-response curves for tumor control were still shallow, suggesting that there are additional causes for heterogeneity of responses among these tumors. CONCLUSIONS: Total dose is important to treatment outcome: After accounting for other treatment variables, there is about a 2% per Gy increase in probability of tumor control over the ranges of control commonly achieved. Overall treatment duration is important. There is at least a 1% per day decrease in tumor control probability if delivery of a constant total dose is prolonged, requiring a compensatory increase in dose by 0.5-0.7 Gy per day to achieve a constant rate of tumor control. Fraction size is not, of itself, an important factor in the response of primary carcinoma of the tonsil. If a tumor has demonstrated a capacity for metastatic spread to lymph nodes, a higher total dose should be considered to achieve control rates at the primary site equivalent to those in node negative patients. Even after accounting for variables such as tumor stage, total dose, and overall treatment duration, there is sufficient heterogeneity in other undocumented determinants of tumor control to cause the tumor control probability curve to be a shallow function of dose.

Analysis of Variance↗

Prognostic factors for local control of early glottic cancer: the Rabin Medical Center retrospective study on 207 patients.

PURPOSE: Different radiation therapy schedules and devices have been used over the last 20 years at Rabin Medical Center in patients with early glottic cancer. The aim of the present retrospective analysis was to identify the subgroup of patients at high risk of failure of radiation treatment. MATERIALS AND METHODS: Between 1974 and 1994, 207 patients with squamous cell carcinoma of the glottis, 182 Stage T1 and 25 Stage T2, underwent definitive radiation therapy. During this period, treatment was administered with different radiation devices (60Co or 6-MV X ray), using different dose/fraction protocols (1.8 or 2 Gy per day, 5 or 6 fractions per week), total doses (42-77.4 Gy), overall radiation times, and delays. These treatment variables, in addition to certain patient and tumor characteristics, were correlated with local control at a median follow-up of 57 months (range 18-265 months). RESULTS: The 5-year local control rates for T1 and T2 tumors were 88% and 73%, respectively. Univariate analysis showed that smoking, diabetes mellitus, anterior commissure involvement, T stage, and extension of tumor to one third or more of the vocal cord were highly significantly correlated with decreased local control. None of the treatment variables, including dosage at which complete tumor regression was noted, were found to be predictive. By multivariate analysis, only anterior commissure involvement was found to be highly significant (risk ratio 1.9, 95% CI 1.2-3.0, p = 0.027), and T stage was borderline significant (risk ratio 1.6, 95% CI 1.0-2.5, p = 0.054). CONCLUSION: This study suggests that only two tumor characteristics are predictive of local failure of early glottic cancer: anterior commissure involvement and T stage. Treatment variables apparently do not influence local control.

Adult↗

Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin.

OBJECT: The maximal tolerated dose (MTD) for stereotactic radiosurgery (SRS) for brain tumors was established by the Radiation Therapy Oncology Group (RTOG) in protocol 90-05, which defined three dose groups based on the maximal tumor diameter. The goal in this retrospective study was to determine whether differences in doses to the margins of brain metastases affect the ability of SRS to achieve local control. METHODS: Between 1997 and 2003, 202 patients harboring 375 tumors that met study entry criteria underwent SRS for treatment of one or multiple brain metastases. The median overall follow-up duration was 10.7 months (range 3-83 months). A dose of 24 Gy to the tumor margin had a significantly lower risk of local failure than 15 or 18 Gy (p = 0.0005; hazard ratio 0.277, confidence interval [CI] 0.134-0.573), whereas the 15- and 18-Gy groups were not significantly different from each other (p = 0.82) in this regard. The 1-year local control rate was 85% (95% CI 78-92%) in tumors treated with 24 Gy, compared with 49% (CI 30-68%) in tumors treated with 18 Gy and 45% (CI 23-67%) in tumors treated with 15 Gy. Overall patient survival was independent of dose to the tumor margin. CONCLUSIONS: Use of the RTOG 90-05 dosing scheme for brain metastases is associated with a variable local control rate. Tumors larger than 2 cm are less effectively controlled than smaller lesions, which can be safely treated with 24 Gy. Prospective evaluations of the relationship between dose to the tumor margin and local control should be performed to confirm these observations.

Adult↗