Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Locale”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,099 records · Page 61Linked to original sources
PubMed1990

Local variability and base sequence effects in DNA crystal structures.

The importance and usefulness of local doublet parameters in understanding sequence dependent effects has been described for A- and B-DNA oligonucleotide crystal structures. Each of the two sets of local parameters described by us in the NUPARM algorithm, namely the local doublet parameters, calculated with reference to the mean z-axis, and the local helical parameters, calculated with reference to the local helix axis, is sufficient to describe the oligonucleotide structures, with the local helical parameters giving a slightly magnified picture of the variations in the structures. The values of local doublet parameters calculated by NUPARM algorithm are similar to those calculated by NEWHELIX90 program, only if the oligonucleotide fragment is not too distorted. The mean values obtained using all the available data for B-DNA crystals are not significantly different from those obtained when a limited data set is used, consisting only of structures with a data resolution of better than 2.4 A and without any bound drug molecule. Thus the variation observed in the oligonucleotide crystals appears to be independent of the quality of their crystallinity. No strong correlation is seen between any pair of local doublet parameters but the local helical parameters are interrelated by geometric relationships. An interesting feature that emerges from this analysis is that the local rise along the z-axis is highly correlated with the difference in the buckle values of the two basepairs in the doublet, as suggested earlier for the dodecamer structures (Bansal and Bhattacharyya, in Structure & Methods: DNA & RNA, Vol. 3 (Eds., R.H. Sarma and M.H. Sarma), pp. 139-153 (1990)). In fact the local rise values become almost constant for both A- and B-forms, if a correction is applied for the buckling of the basepairs. In B-DNA the AA, AT, TA and GA basepair sequences generally have a smaller local rise (3.25 A) compared to the other sequences (3.4 A) and this seems to be an intrinsic feature of basepair stacking interaction and not related to any other local doublet parameter. The roll angles in B-DNA oligonucleotides have small values (less than +/- 8 degrees), while mean local twist varies from 24 degrees to 45 degrees. The CA/TG doublet sequences show two types of preferred geometries, one with positive roll, small positive slide and reduced twist and another with negative roll, large positive slide and increased twist.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗
PubMed2006

Local protein structure prediction using discriminative models.

BACKGROUND: In recent years protein structure prediction methods using local structure information have shown promising improvements. The quality of new fold predictions has risen significantly and in fold recognition incorporation of local structure predictions led to improvements in the accuracy of results. We developed a local structure prediction method to be integrated into either fold recognition or new fold prediction methods. For each local sequence window of a protein sequence the method predicts probability estimates for the sequence to attain particular local structures from a set of predefined local structure candidates. The first step is to define a set of local structure representatives based on clustering recurrent local structures. In the second step a discriminative model is trained to predict the local structure representative given local sequence information. RESULTS: The step of clustering local structures yields an average RMSD quantization error of 1.19 A for 27 structural representatives (for a fragment length of 7 residues). In the prediction step the area under the ROC curve for detection of the 27 classes ranges from 0.68 to 0.88. CONCLUSION: The described method yields probability estimates for local protein structure candidates, giving signals for all kinds of local structure. These local structure predictions can be incorporated either into fold recognition algorithms to improve alignment quality and the overall prediction accuracy or into new fold prediction methods.

Algorithms↗
PubMed1994

Cost-effectiveness of preoperative localization studies in primary hyperparathyroid disease.

OBJECTIVE: To evaluate the effect of preoperative localization studies on the surgical management of patients with primary hyperparathyroid disease (PHPT). SUMMARY BACKGROUND DATA: Reported cure rates of initial surgical exploration for PHPT are close to 95%. Preoperative localization studies are frequently obtained to improve surgical success and decrease operative time. METHODS: Initial cervical exploration was performed in 113 patients with PHPT from 1981 to 1993. Twenty-four patients (21%) had surgery without preoperative localization studies. The remaining 89 patients (79%) had 132 noninvasive preoperative localization studies. Success of the localization studies in tumor localization, pathologic findings, postoperative serum calcium levels, and operative times were compared. Patient costs of the studies were calculated. RESULTS: Disease was identified during operation in 23 of 24 patients (96%) having cervical exploration without preoperative localization studies, and they had normal calcium levels after surgery. Eighty-seven of 89 patients (98%) having preoperative localization studies were surgically cured. The highest sensitivity rate (60%) and highest positive predictive value (79%) of the localization studies were found with thallium-technetium scintiscanning. Average cost of the localization studies was $901 per patient. Combination studies were obtained in 32 patients at an average cost of $1,314 per patient without improving sensitivity. Mean operating time did not differ for localized and nonlocalized patients. CONCLUSIONS: Preoperative localization studies did not improve parathyroid localization or cure rate and did not substantially shorten operating time in initial cervical exploration for PHPT. The economic burden of routine preoperative localization studies in these patients is not justified.

Adult↗
PubMed1989

Prognosis in patients with local recurrence after definitive irradiation for prostatic carcinoma.

Of 414 patients with Stage A2-C disease, all with a minimum follow-up period of 3 years, who have been definitively irradiated by external beam therapy or iodine-125 (I-125) implantation for biopsy-proven prostatic adenocarcinoma, 83 patients (20%) have experienced local recurrences. The incidence of distant metastasis was significantly higher in patients with local tumor recurrence (56 of 83; 68%), as compared with those with local control (64 of 331; 19%; P less than 0.001). This difference remained significant within each tumor grade and stage. Subsequently, survival in patients with local recurrence was significantly shorter than in those with local tumor control (66% vs. 89% at 5 years; P = 0.001). Of the 83 patients with local tumor recurrence, 56 had local recurrence and distant metastasis, and 27 had local failure alone, with a median follow-up of 76 months for the latter group. Fifteen of 83 patients with local recurrence (18%) developed major complications secondary to local disease. Three of the 83 (4%) patients were known to die of prostatic recurrence alone and another 11 of 83 (13%) as a result of some combination of local and distant disease. Therefore, in reference to the entire group of definitively irradiated patients, only 0.72% expired solely of complications associated with local tumor recurrence and an additional 2.7% expired of a combination of both local and distant disease.

Adenocarcinoma↗
PubMed2002

Prognostic factors for death after an isolated local recurrence in patients with early-stage breast carcinoma.

BACKGROUND: The authors analyzed the outcome of patients with early-stage breast carcinoma after an isolated local recurrence, taking into account initial tumor characteristics and the type of initial treatment and local salvage treatment. METHODS: One hundred five patients were studied who presented with a breast tumor measuring <or= 25 mm and who subsequently developed an isolated local recurrence (breast or chest wall) as the first tumor event. A second series included 335 patients who developed distant metastases as the first event. Cox models that took into account potential prognostic factors were used to estimate the risk of death. First, survival rates were compared after an isolated local recurrence and after a diagnosis of distant metastases; and, second, effects of initial treatments and local or systemic treatments of local recurrences were analyzed. RESULTS: The 10-year survival rate was 56% (95% confidence interval, 45-65%) after an isolated local recurrence compared with 9% (95% confidence interval, 7-13%) after distant metastasis as the first event. Three independent prognostic factors for the risk of death after local recurrence were identified: histologic tumor grade, patient age at the time of diagnosis with the primary tumor, and disease free interval until recurrence. The type of initial treatment and local salvage treatment did not influence the risk of death. Systemic treatments of local recurrence had different effects according to the patient's menopausal status. In premenopausal patients, ovarian suppression and chemotherapy significantly decreased the risk of death. In postmenopausal women, systemic treatments did not affect the risk of death. CONCLUSIONS: Isolated local recurrences in patients with early-stage breast carcinoma carry a moderately good prognosis. The outcome of patients is not affected by the type of initial treatment or local salvage treatment. After a local recurrence, ovarian suppression or chemotherapy had a beneficial effect in premenopausal patients.

Adult↗
PubMed2001

Rectal cancer: local recurrence after surgery without radiotherapy.

PURPOSE: This study was designed to assess the local recurrence rate and prognostic factors for local recurrence in patients undergoing curative anterior or abdominoperineal resections without radiotherapy. METHODS: From January 1980 to December 1996, 514 consecutive patients underwent curative resections for rectal cancer. We excluded those with preoperative radiotherapy (n = 23), postoperative radiotherapy (n = 27), local resection (n = 36), and 11 (2.1 percent) patients who died postoperatively. The remaining 417 patients (249 males) with a median age of 64 (range, 21-90) years were analyzed. For upper third lesions, mesorectal tissue was excised down to at least 5 cm below the tumor. Total mesorectal excision was performed for lower and middle tumors. Postoperative chemotherapy was limited to patients with Stage III lesions. Median follow-up (and 95 percent confidence interval) was (5.2 4.3-5.9) years, with 87.7 percent of patients followed up longer than 24 months. Local recurrence was defined as any recurrence within the field of resection, regardless of the presence or absence of distant metastasis. RESULTS: Five-year local recurrence rate(and 95 percent confidence interval) was 9.7 (6.4-13) percent, with a median time to diagnosis of 15 (10-23) months. Local recurrence rates in Stages I, II, and III were: 3.1, 4.1, and 24.1 percent, respectively (P < 0.0001). In relation to node status, local recurrence rates were N0, 4.1 (1.7-6.5) percent; N1, 12.6 (4.6-20.6) percent; N2, 32.1 (12.1-52.1) percent; and N3, 59.3 (22.5-96.1) percent; (P < 0.00001). Lower third tumors had a higher local recurrence rate than middle and upper third tumors: 17.9, 7.1, and 5.1 percent, respectively (P = 0.002). Adjusted by stage, this difference was maintained only in Stage III tumors. Among lower tumors, those at 6 and 7 cm from the anal verge had a lower local recurrence rate than those below 6 cm (6.7 vs. 26.2 percent, respectively; P = 0.02). Accidental rectal perforation at or near the tumor site occurred in 12 cases (2.9 percent), showing a strong correlation with local recurrence (P < 0.0001). Multivariate analysis showed significant higher risk for lower third tumors (hazard ratio, 2.98) and positive nodes (hazard ratio, 4.78). CONCLUSIONS: Appropriate surgery without irradiation achieves excellent local control in N0 rectal cancers. Node metastasis, lower third localization (especially below 6 cm), and accidental rectal perforation at or near the tumor site are significantly associated with a higher local recurrence rate.

Adenocarcinoma↗
PubMed2001

Local recurrence after curative anterior resection with principally blunt dissection for carcinoma of the rectum and rectosigmoid.

PURPOSE: The aim of this study was to determine the incidence of local pelvic recurrence of carcinoma of the rectum and rectosigmoid (tumors where the lower edge is 18 cm or less from the anal verge) in a consecutive series of patients operated on by a single surgeon. All patients underwent curative anterior resection and a formal anatomic dissection of the rectum where mobilization was achieved through a principally careful blunt manual technique along fascial planes, preserving an oncologic package. METHOD: During the period April 1986 to December 1997, 157 consecutive anterior resections for carcinoma of the rectum and rectosigmoid were performed by one surgeon (ALP). One hundred thirty-eight (87.9 percent) were curative, and 19 (12.1 percent) were palliative. The mean follow-up period was 46 +/- 31.6 (range, 2-140) months. Data were retrospectively collated and computer coded by an independent contracted medical research team. Follow-up data were available on all patients. RESULTS: Four (3.1 percent) of the 131 patients undergoing curative anterior resection had local recurrence. Local recurrences occurred between 16 and 38 months from the time of resection, and the cumulative risk of developing local recurrence at five years was 5.2 percent. All tumors in which pelvic recurrence occurred were high grade, and the probability of developing local recurrence at five years for this group was 13.9 percent, which is significantly higher compared with patients who had average or low-grade tumors (P = 0.01). The probability of developing local recurrence at five years for Stage I tumors was 0, Stage II was 5.9 percent, and Stage III was 8.9 percent. In addition, there was a significantly higher incidence of local recurrence in the group of patients undergoing ultralow anterior resection (between 3 and 6 cm from the anal verge) as compared with patients undergoing low or high anterior resection (P = 0.03). Local recurrence developed in 3 of 28 (10.7 percent) patients having ultralow anterior resection, 1 of 57 (1.8 percent) patients having low anterior resection (between 6 and 10 cm from the anal verge), and no patients having high anterior resection (above 10 cm from the anal verge). The clinical anastomotic leak rate for curative anterior resection was 7 of 131 patients (5.3 percent). Thirty-seven of the 131 (28.2 percent) required a proximal defunctioning stoma; 35 (41.2 percent) of these were established for low or ultralow anterior resections and 2 for high anterior resection. The overall five-year cancer-specific survival rate of the entire group of 131 patients was 81.8 percent, and the overall probability of being disease free at five years including both local and distal recurrence was 72.9 percent. Three local recurrences occurred in the 101 patients (77 percent) who did not receive any form of adjuvant therapy. One local recurrence occurred in the 18 patients (13.7 percent) who had adjuvant chemoradiation. No recurrence occurred in the 12 patients (9.2 percent) who had adjuvant chemotherapy alone. CONCLUSION: Curative anterior resection for carcinoma of the rectum and rectosigmoid with principally blunt dissection of the rectum in this study is associated with a 3.1 percent incidence and a 5.2 percent probability at five years of developing local recurrence. Evidence from this study indicates that, as with sharp pelvic dissection, a low incidence and probability of local recurrence can be achieved by a principally blunt mobilization technique through careful attention to preservation of fascial planes in the pelvis and removal of an oncologic package with selective rather than routine adjuvant or neoadjuvant chemoradiation.

Aged↗
PubMed2000

Is local excision adequate therapy for early rectal cancer?

PURPOSE: Radical surgery of rectal cancer is associated with significant morbidity, and some patients with low-lying lesions must accept a permanent colostomy. Several studies have suggested satisfactory tumor control after local excision of early rectal cancer. The purpose of this study was to compare recurrence and survival rates after treating early rectal cancers with local excision and radical surgery. METHODS: One hundred eight patients with T1 and T2 rectal adenocarcinomas treated by transanal excision were compared with 153 patients with T1N0 and T2N0 rectal adenocarcinomas treated with radical surgery. Neither group received adjuvant chemoradiation. Mean follow-up time was 4.4 years after local excision and 4.8 years after radical surgery. RESULTS: The estimated five-year local recurrence rate was 28 percent (18 percent for T1 tumors and 47 percent for T2 tumors) after local excision and 4 percent (none for T1 tumors and 6 percent for T2 tumors) after radical surgery. Overall recurrence was also higher after local excision (21 percent for T1 tumors and 47 percent for T2 tumors) than after radical surgery (9 percent for T1 tumors and 16 percent for T2 tumors). Twenty-four of 27 patients with recurrence after local excision underwent salvage surgery. The estimated five-year overall survival rate was 69 percent after local excision (72 percent for T1 tumors and 65 percent after T2 tumors) and 82 percent after radical surgery (80 percent for T1 tumors and 81 percent for T2 tumors). Differences in survival rate between local excision and radical surgery were statistically significant in patients with T2 tumors. CONCLUSIONS: Local excision of early rectal cancer carries a high risk of local recurrence. Salvage surgery is possible in most patients with local recurrence, but may be effective only in patients with T1 tumors. When compared with radical surgery, local excision may compromise overall survival in patients with T2 rectal cancers.

Adenocarcinoma↗
PubMed2000

Effectiveness of endoluminal sonography in the identification of occult local rectal cancer recurrences.

PURPOSE: Local recurrence of rectal cancer after curative surgery appears in 5 to 30 percent of all cases. It is necessary to detect local recurrence in a resectable stage to have an opportunity for curative reintervention or palliative prevention of those symptoms. Because most local recurrences occur extraluminally, conventional follow-up fails to detect them at an early stage. Therefore, a prospective study was performed to assess the diagnostic potential of endorectal and endovaginal ultrasound to detect asymptomatic resectable local recurrence. METHODS: In 338 patients 721 endoluminal ultrasound examinations were added to routine follow-up of rectal and left colonic cancer, with a mean of 2.1 (range, 1-10) endoluminal ultrasound examinations for each patient. RESULTS: A total of 116 patients (34.3 percent) were shown to have local recurrence, which was suggested by endoluminal ultrasound and proven by endoluminal ultrasound-guided needle biopsy in all cases of unclear pararectal structures that could not be verified by endoscopic biopsy. Digital examination failed to detect local recurrence in 91 patients, endoscopy failed to detect local recurrence in 80 patients, and the levels of tumor markers were normal in 25 patients with confirmed local recurrence. In 33 cases of local recurrence, both digital examination and endoscopy results were normal. Twenty-five patients, in whom carcinoembryonic antigen levels, digital examination, and endoscopy results were normal, underwent potential curative reoperation, with total resection of the local recurrence. All 25 patients were still alive at the end of the study period, and 21 were free from disease. On the other hand, only 6 of 67 patients with local recurrence detectable by conventional follow-up could be operated on with curative intention. CONCLUSION: Postoperative endoluminal ultrasound is able to detect local recurrence at an earlier and asymptomatic stage and can be verified by endosonography-guided needle biopsy. Routine use in follow-up may raise the ratio of curative retreatment by early detection of extramural local recurrence.

Adolescent↗
PubMed2001

Prognostic significance of local recurrence in breast cancer after postmastectomy radiotherapy.

PURPOSE: We have retrospectively analyzed the impact of local recurrence in patients with adjuvant radiation therapy after mastectomy for breast cancer. PATIENTS AND METHODS: From January 1985 through December 1993, 959 patients were irradiated after mastectomy for breast cancer. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3-12.2 years). 368 (38%) were pre- and 591 (62%) postmenopausal. 35% had T3-4 tumors, 62% had axillary lymph node involvement, and 66% received additional systemic hormonal and/or cytotoxic therapy. Postmastectomy radiotherapy was administered in case of positive axillary nodes and in high-risk pN0-patients. The chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field with 50 Gy and the chest wall with an electron field with 44 Gy in 2-Gy fractions. RESULTS: The overall survival was 70.5% after 5 and 59.8% after 10 years. 53 patients (5.5%) developed a locoregional recurrence 2-96 months after treatment (median 26 months). The local control rate was 92.7% after 5 and 86.4% after 10 years. Axillary lymph node involvement was the most important and (in a multivariate analysis the only) risk factor for local recurrence (p = 0.0001). Patients with local control had a significantly better 10-year distant-disease-free survival and overall survival as compared to patients with local recurrence (44.5% vs 15.4%, p = 0.002 and 62.1% vs 34.8%, p = 0.004). Local recurrence increased the risk of death by a factor of 1.7 and in a Cox regression model, axillary lymph node status, T-category and local recurrence were significant prognostic factors for overall survival. In patients with local recurrence, the initial axillary lymph node status was the most important prognostic factor for survival after local recurrence. The 3-year survival after local relapse was 86% for patients with pN0 status vs 27% in with positive axillary nodes (p = 0.025). CONCLUSIONS: Local recurrence after treatment of breast cancer with mastectomy + radiotherapy +/- systemic therapy is associated with a significantly higher risk of distant metastases and death. In this analysis, local recurrence was a strong and, besides lymph node status and T category, an independent risk factor for survival. Minimizing the risk of local recurrence is therefore an essential goal of a curative treatment concept.

Adult↗
PubMed1984

Adsorption of local anesthetics on phospholipid membranes.

In order to elucidate various types of adsorption modes of local anesthetics in membranes, a study of local anesthetic adsorption on lipid membranes was made by measuring electrophoretic mobility of phospholipid vesicles in the presence of local anesthetics of various concentrations in the vesicle suspension solution. The amounts of local anesthetics to be adsorbed on the membrane surface were deduced from the electrophoretic mobility of a phosphatidylcholine vesicle at various concentrations of the cationic form of local anesthetics. The order of surface adsorption of local anesthetic was dibucaine greater than tetracaine greater than procaine. A surface partition coefficient, Ks = 1/ACs, was introduced, where A is the membrane surface area per local anesthetic molecule adsorbed and Cs the surface concentration of local anesthetics. The amounts of local anesthetic adsorbed on phosphatidylserine membrane were much greater than that of the phosphatidylcholine membrane. It was deduced that the major factor for this large adsorption was due to the enhancement of cationic forms of local anesthetic concentrations at the charged membrane surface. Divalent cations inhibited such surface adsorption of local anesthetics by reducing surface concentrations of local anesthetics where the surface potential of the negatively charged membrane surface was influenced by the presence of divalent cations in the solution as well as by the reduction of fixed surface charges due to divalent cation binding. Some association modes of local anesthetics on nerve membranes are discussed with the results obtained in the above adsorption study.

Adsorption↗
PubMed1983

Prognostic factors of inoperable localized lung cancer treated by high dose radiotherapy.

A retrospective study was made of the results of high dose radiotherapy (greater than or equal to 50 Gy) given to 171 patients with inoperable, intrathoracic non small cell lung cancer from January 1971-April 1973. Local control was dependent on the total tumor dose: after one year local control was 63% for patients treated with greater than 65 Gy, the two year local control was 35%. If treated with less than 65 Gy the one year local control was less than or equal to 40%. Tumor doses correlated with the size of the booster field. If the size of the booster field was less than 100 cm2, the one year local control was 72%; the two year local control was 44%. Local control was also influenced by the performance status, by the localization of the primary tumor in the left upper lobe and in the periphery of the lung. Local control for tumors in the left upper lobe and in the periphery of the lung was about 70% after one year, and about 40% after two years. The one and two years survival results were correlated with the factors influencing local control. The dose factor, the localization factors and the performance influenced local control independently. Tumors localized in the left upper lobe did metastasize less than tumors in the lower lobe, or in a combination of the two. This was not true for the right upper lobe. No correlation between the TNM system, pathology and the prognosis were found.

Adenocarcinoma↗
PubMed1984

Local failure following curative resection of colonic adenocarcinoma.

A retrospective review of the medical records of 533 patients undergoing resection with curative intent of large bowel above the peritoneal reflection was undertaken to identify subsets of patients at high risk for local failure. The overall local failure rate was 102/533 (19%) with 32/102 patients having local failure only and 70/102 patients having concurrent local failure and distant metastases. Pathological confirmation of local failure was obtained in 79% of the cases and by surgical exploration in 75%. Overall local failure rates increased with advancing stage of disease. Tumors staged B3, C2 and C3 all had local failure rates in excess of 30%, whereas for Stage A, B1, B2 and C1 lesions, the incidence of local failure was less than 4%. Stage B2 tumors arising in high and low sigmoid and splenic and hepatic flexure had a moderate incidence of local failure (21%) compared to low incidence (5%) at all other sites. The majority of local and regional failures 84/102 (82%) occurred in tumor bed and adjacent soft tissues whereas only 18/102 (18%) local failures occurred in regional nodal groups. The overall local failure rate increased from 27% with one lymph node involved to 50% with greater than 5 lymph nodes involved. Patients with Stage B3, C2 and C3 colon tumors at all sites and selected B2 tumors have a high rate of local failure after surgical resection. The value of postoperative radiotherapy should be formally studied in these patients.

Adenocarcinoma↗
PubMed2004

[Isolate local failure after breast-conserving treatment for early breast cancer, about 57 cases].

PURPOSE: - To identify predicting factors of local control and survival after isolate local failure by statistical analysis of the data after breast-conserving treatment for early breast cancer. METHODS AND PATIENTS: - In time of local failure, mean age was 54.7 years old, mean tumor size was 19.3 mm and recurrence was more often infiltrating ductal carcinoma (88%). Local recurrence was unifocal in 44 cases and localised outside of the site of the primary tumorectomy in 35 cases. Local failure treatment was a radical mastectomy or parietectomy (53 patients). Hormonotherapy was delivered in 36 patients and chemotherapy was delivered in 26 patients. Mean follow-up was 62 months. RESULTS: - Fifteen patients developed second local recurrence in a mean time of 36 months. Five years local control rate was 68% after the first local failure. Surgery treatment (non-conservative surgery vs. conservative surgery) was the only factor which influenced local control. Six patients developed homolateral axillary and/or supraclavicular node recurrence. Twelve patients underwent metastasis in a mean time of 36 months after the first local recurrence. Five years metastasis free survival rate was 80%. Peritumoral vascular invasion in time of the first local failure increased metastasis risk and node recurrence. Second local failure did not alter metastasis free survival. CONCLUSION: - Peritumoral vascular invasion in time of the first local failure decreased node and metastasis free survival. Surgery should be radical, but the place of chemotherapy and hormonotherapy was not definite.

Adult↗
PubMed2006

Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: A multicentric phase II study.

PURPOSE: The combination of irradiation and total mesorectal excision for rectal carcinoma has significantly lowered the incidence of local recurrence. However, a new problem is represented by the patient with locally recurrent cancer who has received previous irradiation to the pelvis. In these patients, local recurrence is very often not easily resectable and reirradiation is expected to be associated with a high risk of late toxicity. The aim of this multicenter phase II study is to evaluate the response rate, resectability rate, local control, and treatment-related toxicity of preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis. METHODS AND MATERIALS: Patients with histologically proven pelvic recurrence of rectal carcinoma, with the absence of extrapelvic disease or bony involvement and previous pelvic irradiation with doses < or =55 Gy; age > or =18 years; performance status (PS) (Karnofsky) > or =60, and who gave institutional review board-approved written informed consent were treated by preoperative chemoradiation. Radiotherapy was delivered to a planning target volume (PTV2) including the gross tumor volume (GTV) plus a 4-cm margin, with a dose of 30 Gy (1.2 Gy twice daily with a minimum 6-h interval). A boost was delivered, with the same fractionation schedule, to a PTV1 including the GTV plus a 2-cm margin (10.8 Gy). During the radiation treatment, concurrent chemotherapy was delivered (5-fluorouracil, protracted intravenous infusion, 225 mg/m(2)/day, 7 days per week). Four to 6 weeks after the end of chemoradiation, patients were evaluated for tumor resectability, and, when feasible, surgical resection of recurrence was performed between 6-8 weeks from the end of chemoradiation. Adjuvant chemotherapy was prescribed to all patients, using Raltitrexed, 3 mg/square meter (sm), every 3 weeks, for a total of 5 cycles. Patients were staged using the computed tomography (CT)-based F-classification (F0: no side-wall involvement; F1, F2, F3: 1, 2, and 3-4 side-walls involved, respectively). Toxicity was evaluated on the basis of the Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: Fifty-nine patients (38 male, 21 female; median age, 62 years; range, 43-77 years) were enrolled in the study, by 12 different Italian radiotherapy departments. Previous surgery was anterior resection in 45 patients (76.3%) and abdominal-perineal resection in 14 patients (23.7%); previous radiotherapy dosage ranged between 30 and 55 Gy (median, 50.4 Gy); the median interval between prior radiation therapy to the onset of reirradiation was 27 months (range, 9-106 months); 44 patients (74.6%) had received some form of previous chemotherapy (concurrent and/or adjuvant). Fifty-one of 59 patients (86.4%) completed chemoradiation without treatment interruptions: 6 patients (10.2%) had temporary treatment interruption due to toxicity or patient compliance, and 2 patients (3.4%) had definitive treatment interruption. The incidence of Grade 3 lower gastrointestinal acute toxicity was only 5.1%. No patient developed Grade 4 acute toxicity. After chemoradiation, 5 patients (8.5%) had complete response (CR), 21 patients (35.6%) had partial response (PR), 31 patients (52.6%) had no change (NC) and 2 patients (3.4%) showed progressive disease (PD). Overall, the response rate (PR + CR) was 44.1% (95% confidence interval, 29.0-58.9%). Twenty of 24 patients (83.3%) with pelvic pain before treatment had symptomatic response. Tumor resection was performed in 30 of 59 patients (50.8%) including 2 local excisions, 4 anterior resections, 18 abdominoperineal resections, and 6 other. Surgical resection resulted as R0 and R1 in 21 patients (35.6%) and 3 patients (5.1%), respectively. The possibility of radical resection was influenced by tumor response to chemoradiation (PD/NC: 7/33; PR/CR: 14/26; p = 0.009). Thirty-three patients received adjuvant chemotherapy, which was completed in 30 (50.8%). At a median follow-up of 36 months (range, 9-69 months), 28 patients (47.5%) developed local recurrence or tumor progression in the unresected pelvic disease and 18 patients (30.5%) developed distant metastasis. Seven patients showed late toxicity, including 2 skin fibrosis, 2 impotence, 2 urinary complications requiring nephrostomy, and 1 small bowel fistula requiring surgical diversion. Overall median survival was 42 months. Five-year actuarial survival was 39.3%; 66.8% in R0 resected patients and 22.3% in patients treated without surgery or undergoing subtotal tumor removal. Local control and disease-free survival were significantly correlated with the interval between surgical treatment for primary tumor and local recurrence (p = 0.028 and p = 0.003, respectively). Radical resection significantly influenced local control, disease-free survival, and overall survival (p = 0.010, p = 0.010, and p = 0.050 respectively). The multivariate analysis confirmed the impact of surgery-relapse interval on local control (p = 0.016) and disease-free survival (p = 0.002), and confirmed the correlation between R0 surgery with local control and disease-free survival (p = 0.016). CONCLUSIONS: Use of hyperfractionated chemoradiation was associated with a low rate of acute toxicity and an acceptable incidence of late complications. Pain control was excellent. The overall 5-year survival was 39%. Despite 87.4% of patients having F1-3 stage disease, approximately one-third (35%) achieved R0 resection, and two-thirds of patients in this cohort of patients were alive at the 5-year mark. However, further studies using innovative treatment algorithms are warranted to, hopefully, improve the local tumor response and control.

Adult↗
PubMed2001

Local excision and postoperative radiotherapy for distal rectal cancer.

PURPOSE: To assess the outcome following local excision and postoperative radiotherapy (RT) for distal rectal carcinoma. MATERIALS AND METHODS: Seventy-three patients received postoperative radiotherapy following local surgery for primary rectal carcinoma at Princess Margaret Hospital from 1983 to 1998. Selection factors for postoperative RT were patient preference, poor operative risks, and "elective" where conservative therapy was regarded as optimal therapy. Median distance of the primary lesion from the anal verge was 4 cm (range, 1--8 cm). There were 24 T1, 36 T2, and 8 T3 lesions. The T category could not be determined in 5. Of 55 tumor specimens in which margins could be adequately assessed, they were positive in 18. RT was delivered using multiple fields by 6- to 25-MV photons. Median tumor dose was 50 Gy (range, 38--60 Gy), and 62 patients received 50 Gy in 2.5-Gy daily fractions. The tumor volume included the primary with 3--5 cm margins. No patients received adjuvant chemotherapy. Median follow-up was 48 months (range, 10--165 months). RESULTS: Overall 5-year survival and disease-free survival were 67% and 55%, respectively. Tumor recurrence was observed in 23 patients. There were 14 isolated local relapses; 6 patients developed local and distant disease; and 3 relapsed distantly only. For patients with T1, T2, and T3 lesions, 5-year local relapse-free rates were 61%, 75%, and 78%, respectively, and 5-year survival rates were 76%, 58%, and 33%, respectively. The 5-year local relapse-free rate was lower in the presence of lymphovascular invasion (LVI) compared to no LVI, 52% vs. 89%, p = 0.03, or where tumor fragmentation occurred during local excision compared to no fragmentation, 51% vs. 76%, p = 0.02. Eleven of 14 patients with local relapse only underwent abdominoperineal resection, 8 achieved local control, and 4 remained cancer free. The ultimate local control, including salvage surgery, was 86% at 5 and 10 years. The 5-year colostomy-free rate was 82%. There were 2 patients who experienced RTOG Grade 3 late complications, and 1 with Grade 4 complication (bowel obstruction requiring surgery). CONCLUSION: The local relapse rate for patients with T1 disease was high compared to other series of local excision and postoperative RT. Patients with LVI or tumor fragmentation during excision have high local relapse rates and may not be good candidates for conservative surgery and postoperative RT.

Adenocarcinoma↗
PubMed1998

How successful is high-dose (> or = 60 Gy) reirradiation using mainly external beams in salvaging local failures of nasopharyngeal carcinoma?

PURPOSE: To evaluate the efficacy of high-dose (> or = 60 Gy) reirradiation using mainly external beams in salvaging local failures of nasopharyngeal carcinoma (NPC) after modern primary radical radiotherapy that delivered radical dose-to-target volumes defined by CT scan. METHODS AND MATERIALS: Nine hundred and three patients with nondisseminated NPC whose primary radical radiotherapy was administered between 1984 and 1989 inclusive were studied. One hundred and seventy-six had local failures comprising 9 persistences and 167 recurrences. In 10 patients the local failures were preceded or accompanied by (within 2 months) distant metastases, and these were given supportive treatment or palliative radiotherapy in low dose (< 60 Gy) if symptomatic. Most of the rest (123 of 166) were treated with either reirradiation to high dose (> or = 60 Gy) using mainly external photon beams (n = 103) or nasopharyngectomy with/without radical neck dissection with/without postoperative radiotherapy (n = 20). The remainder (n = 43) received only palliative treatments because of poor general condition and/or patients' refusal of radical treatments. The primary radiotherapy was planned on the basis of target volumes defined by CT scan and given to a standard nasopharyngeal dose of 62.5 Gy/29 fractions/6 weeks. In the presence of parapharyngeal involvement, an additional boost of 20 Gy/10 fractions/2 weeks was given via a posterior oblique photon beam. If local residual tumors were diagnosed at 4-6 weeks after the completion of external radiotherapy, an additional boost of 24 Gy/3 fractions/15 days was given by intracavitary intubation. For the local failures given high-dose reirradiation, the target volume was defined by CT scan and treated by a two-field or a three-field photon arrangement with or without additional dose supplement by intracavitary intubation. Nasopharyngectomy was performed via the transcervico-mandibulo-palatal approach or the maxillary swing approach. Radical neck dissection was only performed for the clinically evident nodal failures. RESULTS: With a median follow-up of 20 months (range 2.5-81 months) since the diagnosis of local failure, the actuarial 5-year overall survival, further relapse-free survival and free-from-local-tumor rates were 9.4, 11.5, and 18.7%, respectively, for the 123 patients treated by either high-dose reirradiation (n = 103) or nasopharyngectomy (n = 20). Palliatively treated patients (n = 43) had a survival comparable to patients whose local failures were preceded or accompanied by distant metastasis (n = 10). Reirradiation to high dose (> or = 60 Gy) mainly by external photon beams achieved a 5-year overall survival of 7.6% and 5-year local control of 15.2% with significant complications. Radiation-induced temporal lobe encephalopathy was radiologically evident in 21 patients (20.4%), and 13 of these 21 patients were symptomatic. It could have been the cause of death in three patients who also suffered from uncontrolled local tumor. Significant morbidity was also associated with the other frequent radiation complications, including xerostomia, trismus, and deafness. Uni- and multivariate analyses indicated that brief initial disease-free interval between completion of primary radiotherapy and diagnosis of local failures and advanced recurrent T-stage and recurrent N-stage were significant prognosticators predicting poor survival and/or further local failure after reirradiation. These patients were unlikely to benefit from the treatment. Nasopharyngectomy (+/- neck dissection +/- postoperative radiotherapy) was associated with earlier recurrent T-stages (mostly rT1 and rT2) and better survival and local control than reirradiation. However, restricting the comparison to rT1 and rT2 still demonstrated the superior results in favor of nasopharyngectomy, which could not be explained by the selection of less advanced lesions or patients with better performance status for surgery. (ABSTRACT TRUNCATED)

Adult↗
PubMed1997

Adjuvant radiation for vulvar carcinoma: improved local control.

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.

Adult↗