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Selected AbstractsAdjuvant fractionated high-dose-rate intracavitary brachytherapy after external beam radiotherapy in Tl and T2 nasopharyngeal carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2004Jiade J. Lu MD Abstract Background. The value of high-dose-rate intracavitary brachytherapy (HDRIB) for persistent or recurrent nasopharyngeal carcinoma has been well described; however, the benefit of routine adjuvant fractionated HDRIB following external beam radiation therapy (EBRT) has not been completely determined. The objective of this analysis was to evaluate the outcome of two fractions of adjuvant HDRIB treatment in Tl and T2 nasopharyngeal carcinoma. Methods. Thirty-three consecutive and nonselected patients who had Tl and T2 non-disseminated nasopharyngeal carcinoma were treated according to an IRB approved institutional research protocol between March 1999 and July 2001. By the 1997 AJCC cancer staging classification, 22 patients (67%) had Tl disease and 11 patients (33%) had T2 disease. Seventeen of these patients who had stage I or stage II disease (i.e., NO or Nl) were treated with EBRT followed by two fractions of adjuvant HDRIB (group 1); 16 patients who had stage III or stage IV disease (i.e., N2 or N3) were treated with concurrent cisplatin, EBRT and adjuvant HDRIB and subsequent adjuvant cisplatin and fluorouracil (5-FU) chemotherapy (group 2). EBRT was delivered by daily conventional fractionation to a total dose of 66 Gy to the primary tumor. Nodal disease received 66 Gy if it was less than 3cm in maximum diameter and 70 Gy if larger or there was palpable residual disease after 66 Gy. A total of 10 Gy of HDRIB in 2 equal fractions of 5 Gy spaced 1 week apart was delivered starting 1 week after the completion of EBRT. All patients were assessed for treatment response, local control, survival, and toxicity. Results. The median follow up for all 29 surviving patients is 29 months (range: 17,38 months). One patient died 7 months and one died 18 months after radiation therapy from the effects of distant metastases; two died of unrelated causes. At the time of this analysis, one patient (3%) had persistent local disease and one patient (3%) developed pathologically confirmed local recurrence in the nasopharynx. In addition, one patient (3%) developed recurrence only in a neck node followed by distant metastasis, and two patients (6%) developed distant metastasis without locoregional relapse. The 2-year local control rate at the primary site was 93.6%, and the overall survival and disease-free survival rates were 82% and 74% respectively. All patients experienced some degree of acute and/or late toxicity related to radiation therapy. Ten patients (30%) experienced grade 3 acute and/or late toxicity and six patients (18%) developed grade 4 acute and/or late toxicity. No grade 5 toxicity occurred. No unexpected damage of structures within the HDRIB fields was detected. Conclusions. EBRT supplemented by two fractions of adjuvant HDRIB produced a 93.6% local control rate for Tl and T2 nasopharyngeal cancer at 2 years of follow up, with acceptable rates of acute and late toxicity. Brief adjuvant HDRIB appears to permit dose escalation safely, even in patients who receive chemotherapy concurrently with conventional radiation therapy. This strategy needs to be optimized and then tested in a prospective randomized phase III trial to learn if it can improve outcome. © 2004 Wiley Periodicals, Inc. Head Neck26: 389,395, 2004. [source] Per-operative frozen section examination of pelvic nodes is unnecessary for the majority of clinically localized prostate cancers in the prostate-specific antigen eraINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2000Yoshiyuki Kakehi Abstract Background: The incidence of unsuspected lymph node metastasis seems to be decreasing in the prostate-specific antigen (PSA) era. It remains controversial as to whether routine pelvic lymph node dissection and per-operative frozen section examination should be performed. In addition, it is still unclear whether an aggressive approach to local disease by surgery or irradiation confers survival benefits on stage D1 patients. Methods: Eighty-eight consecutive patients with clinically localized prostate cancer who underwent pelvic lymph node dissection prior to radical prostatectomy during the period between 1985 and 1998 were analyzed. The incidence of lymph node metastases after 1992 was compared with that before 1992. Sensitivity and specificity of frozen section examination was assessed. Progression-free survival and cause-specific survival curves of node-positive patients who underwent radical prostatectomy were estimated by the Kaplan,Meier method. Results: Six of 17 patients (35.3%) treated before 1992 and five of 71 patients (7.0%) treated after 1992 showed unsuspected lymph node metastasis (P = 0.0059). Eight of 11 node-positive patients underwent radical prostatectomy and two have so far demonstrated clinical progression and cancer death with a median follow-up period of 63 months. The 5 year progression-free rate and the cause-specific survival rate for these patients were 71.4 and 85.7%, respectively. Sensitivity of frozen section examination for micrometastasis and gross-metastasis cases, respectively, was 3/6 (50%) and 4/4 (100%), while specificity was 85/85 (100%). Conclusions: The incidence of unsuspected lymph node metastases has been significantly decreased in the PSA era. Frozen section examination of pelvic nodes can be omitted and radical prostatectomy is an acceptable choice of treatment in patients without macroscopically apparent nodal metastases. [source] Review article: oral ulcers and its relevance to systemic disordersALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2005S. R. Porter Summary Oral ulceration is a common problem, and is sometimes a marker of gastroenterological disease. Patients with signs or symptoms of oral ulcers are sometimes referred to gastroenterology clinics, however, in most instances the ulcers does not reflect gastrointestinal disease. Indeed, a spectrum of disorders other than those of the gut can give rise to oral mucosal ulcers ranging from minor local trauma to significant local disease such as malignancy or systemic illness. This present article reviews aspects of the aetiology, diagnosis and management of common ulcerative disorders of the oral mucosa. [source] Conjunctival Melanoma: The Role of Conservative Surgery and Radiotherapy in Regional Metastatic DiseaseTHE LARYNGOSCOPE, Issue 5 2005Taran Tatla MRCS Abstract Objective: To evaluate prognostic factors and determine the role of conservative surgery and radiotherapy in managing metastatic conjunctival malignant melanoma (MM) involving preauricular/submandibular lymph nodes. Method: A retrospective analysis (1990,2003) of clinical and histopathologic data from 12 patients presenting with regional metastases after failed local treatment for conjunctival MM. Patients received a common, multispecialty, conservative management approach: wide local excision, topical cryotherapy or radiotherapy to conjunctival MM (orbital exenteration for more advanced local disease), lumpectomy, and adjuvant "ring" radiotherapy of regional metastases, with chemotherapy for distant metastases. Results: Median age at primary diagnosis was 51 (range 28,86) years with equal sex predilection. Six of the 12 patients had primary tumors of the bulbar conjunctiva; the remainder arose in the palpebral conjunctiva, the caruncle, or the fornix. Of 11 originating in primary acquired melanosis (PAM), 2 were amelanotic. Epithelioid tumor cells were noted histologically in seven of eight specimens in which cell type could be determined. Eight tumors metastasised to preauricular nodes, three to submandibular and one to both, with a median interval of 23 (range 12,108) months after primary diagnosis. After conservative surgery and "ring irradiation," 7 of 12 patients remained free of regional nodal relapse at median interval of 16 (range 3,126) months. Five patients developed regional nodal recurrence at median interval of 11 (range 6,13) months, 3 of whom were within radiotherapy portals. Eight patients developed distant metastasis at median interval of 44 (range 22,138) months. Eleven patients had tumor-related death. The mean Kaplan-Meier adjusted survival time after primary diagnosis was 76 months with death ensuing postregional metastasis within a median 18 (range 4,127) months. The sole survivor's follow-up duration was 56 months. Conclusion: Locoregional metastasis after treatment for conjunctival MM is associated with a poor prognosis. Both epithelioid tumor cells and PAM are associated with disseminating disease and poorer outcome. Literature review has failed to demonstrate advantages of mutilating radical surgery over a conservative approach in this rare disease. [source] External Beam Radiation Followed by Planned Neck Dissection and Brachytherapy for Base of Tongue Squamous Cell Carcinoma,THE LARYNGOSCOPE, Issue 10 2000David M. Kaylie MD Abstract Background Surgical resection of tongue base cancer can leave the patient with significant functional deficits. Other therapies, such as external beam radiation followed by neck dissection and radiation implants, have shown equal tumor control with good functional outcome. Methods Between March 1991 and July 1999, 12 patients at Oregon Health Sciences University, the Portland Veterans Administration Medical Center and West Virginia University School of Medicine Hospital were treated with external beam radiation followed by neck dissection and Ir192 implants. Two patients had T1 disease, two had T2, five patients had T3 tumors, and three had T4 tumors. Six had N2a necks, three had N2b necks, and three had N2c. Follow-up ranged from 13 months to 8 years. Results After external beam radiation, five patients had complete response and seven had partial response in the neck without complications. One patient underwent a unilateral radical neck dissection, eight had unilateral selective neck dissections involving levels I to IV, and three had dissections involving levels I to III. One of the five patients who had a complete clinical response in the neck had pathologically positive nodes. One patient had a pulmonary embolus that was treated and had no permanent sequelae. There were three complications from brachytherapy. Two patients had soft tissue necrosis at the primary site and one patient had radionecrosis of the mandible. All healed without further therapy. One patient had persistent disease and underwent a partial glossectomy but died of local disease. Distant metastasis developed in two patients. All others show no evidence of disease and are able to eat a normal diet by mouth. Conclusion This combination of therapies should be considered when treating tongue base cancer. [source] Clinical utility of magnetic resonance imaging and the preoperative identification of low risk endometrial cancerAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 5 2004Giovanni LOSCO Abstract Background:, Magnetic resonance imaging (MRI) is reported to offer the best imaging of local disease in endometrial cancer. We audited MRI scans to identify their clinical utility, particularly in the preoperative identification of ,low risk' endometrial cancer (grade one or two endometrioid tumours confined to the inner half of the myometrium). Aim:, To correlate histological and MRI findings and to establish our ability to preoperatively identify women with ,low risk' tumours. Study design:, A retrospective audit of MRI scans in women with a new diagnosis of endometrial cancer from July 1998 to November 2002. Radiology and pathology reports and surgical staging data were extracted. Independently a team of radiologists reviewed MRI films and the findings were compared to pathology. Results:, Thirty-nine patients were included. Only 10% of original reports contained all the clinically relevant information. On review, the sensitivity for the detection of myometrial invasion was 90%, specificity 71%, positive predictive value (PPV) 93% and negative predictive value (NPV) 63%. For the detection of deep invasion, sensitivity was 56%, specificity 77%, PPV 64% and NPV 71%. All women with grade one or two tumours having no invasion or grade one having superficial invasion detected on MRI had pathological ,low risk' disease. Conclusions:, Magnetic resonance imaging scans as reported offered limited clinical benefit. Attention needs to be given to MRI sequencing and reporting protocols. If the review results can be confirmed by prospective studies, MRI offers significant clinical utility in the identification of low risk patients and their surgical treatment planning. [source] Systemic therapy for advancing or metastatic prostate cancer (STAMPEDE): a multi-arm, multistage randomized controlled trialBJU INTERNATIONAL, Issue 4 2009Nicholas D. James There is a need to improve the outcomes for men with high-risk localised, nodal or metastatic prostate cancer, or with aggressively relapsing disease after initial therapy for local disease. This group of men is currently managed with long-term hormone therapy. Thus we aim to evaluate the toxicity and efficacy of three different systemic therapies (docetaxel, zoledronic acid and celecoxib) used alone or combined at the initiation of hormone manipulation for high-risk prostate cancer. A novel statistical design (multi-arm, multistage method) simultaneously tests multiple distinct strategies in parallel against a single control arm. The trial has several ,stages', from initial confirmation of safety to a phase III assessment of survival, with a series of intervening activity stages. This method provides a means of assessing several agents more quickly and efficiently, and allows inactive treatments to be dropped from further study at an early stage. STAMPEDE has been designed to address in parallel the activity and efficacy of these agents for this patient group. It is a flagship randomized clinical trial for academic research into prostate cancer in the UK. More than 500 patients have been recruited on schedule, confirming the acceptability of this complex trial design to patients and clinicians. The trial targets a population of ,3000 patients. STAMPEDE is a major new trial with a novel design applicable to the synchronous testing of several agents. It is hoped that the results will improve outcomes for patients with high-risk prostate cancer. The design could be applicable to the study of new therapies in other cancer types. Continued efforts are required by the urological cancer community to maintain the excellent recruitment shown to date. [source] Long-term prognosis of children with papillary thyroid cancer presenting with pulmonary metastasesBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 9 2000J. Brink Background Papillary thyroid cancer (PTC) has a generally favourable prognosis, but elderly patients with distant metastases or extracapsular invasion fair poorly. In small studies with short follow-up, young patients presenting with such extracapsular invasion and pulmonary metastases have faired well. This retrospective study was undertaken to clarify the long-term prognosis of such patients with advanced PTC. Methods Twenty-one children and young adults (median age 14 (range 6,20) years) presenting with PTC and pulmonary metastases were treated at a single institution between 1947 and 1998. Mean maximal tumour diameter was 4·65 cm. Initial surgical treatment consisted of total thyroidectomy (n = 16), subtotal thyroidectomy (n = 4) and isthmectomy (n = 1), coupled with a variety of lymph node dissections (n = 20). After operation, 19 patients were treated with ablative and incremental doses of iodine-131 until disease free. All patients were placed on suppressive thyroid hormone after operation. Mean length of follow-up was 21 years (range 3 months to 47 years). Follow-up was less than 3 years in four patients. All patients have undergone post-treatment radionucleotide and radiological evaluation. Results Nine of the 21 patients developed recurrent disease. The risk of recurrence at 5 years was 39 (95 per cent confidence interval 14,57) per cent. Eight had cervical lymph node recurrence and no patient developed recurrent pulmonary disease. All patients with identifiable recurrent disease underwent selective lymph node resection, which involved multiple resections in four. At follow-up, 18 patients remain completely free of disease, one patient has recurrent cervical node disease and two patients have died. The disease-free survival at 5 years was 95 (95 per cent confidence interval 86,100) per cent. Cause-specific death occurred in a single patient who died from extensive local disease at age 29 years after 12 years of multiple cervical lymph node recurrences. Conclusion A stepwise treatment approach including total thyroidectomy, high-dose iodine-131 treatment and early surgical reintervention for suspected local recurrent disease allows long-term survival and frequent ,cure' for young patients with PTC and concomitant pulmonary metastases. © 2000 British Journal of Surgery Society Ltd [source] Preoperative staging of rectal cancer allows selection of patients for preoperative radiotherapyBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 5 2000A. F. Horgan Background: Variability in rates of local recurrence following resection of rectal cancer has led to the suggestion that all patients should undergo preoperative radiotherapy. This centre employs a selective policy of radiotherapy only in patients with evidence of advanced local disease determined by preoperative staging. Methods: A retrospective review was carried out of 114 consecutive patients with rectal cancer. Patients were divided before operation into palliative and curative groups based on preoperative staging. Only patients in the palliative group were offered preoperative radiotherapy. Total mesorectal excision (TME) was performed for all tumours of the middle or lower rectum. Results: The perioperative mortality rate was 0·9 per cent and anastomotic dehiscence occurred in 2·8 per cent. Local recurrence developed in 4 per cent of patients in the ,curative' group and in seven of 15 of those assigned to the palliative group before operation (P < 0·01). Positive lateral resection margins were significantly associated with a risk of subsequent recurrence (ten of 13 versus three (3 per cent) of 93; P < 0·001). Conclusion: Preoperative adjuvant radiotherapy can be omitted reasonably in patients in whom there is no evidence of locally advanced disease, provided that adequate surgery, incorporating TME for low tumours, is performed. © 2000 British Journal of Surgery Society Ltd [source] Survival in patients with brain metastases from breast cancerCANCER, Issue 11 2008The importance of HER-2 status Abstract BACKGROUND Brain metastases (BM) are the most common intracranial tumors in adults. To the authors' knowledge, established prognostic factors for survival after the diagnosis of BM in breast cancer patients do not take into account HER,2 status, which may have increasing relevance in the trastuzumab therapy era. METHODS The authors identified 83 patients with breast cancer and new parenchymal BM diagnosed between January 1, 2001 and December 31, 2005 who were treated at Massachusetts General Hospital. Survival was estimated using the Kaplan-Meier method and curves were compared using the log-rank test. A Cox proportional hazards model was used to determine independent predictors of survival. RESULTS The median overall survival from the time of BM was 8.3 months. On univariate analysis, HER-2-positive patients were found to have prolonged survival after BM compared with HER-2-negative patients (17.1 months vs 5.2 months). Patients with triple negative disease had a median survival of 4.0 months, compared with 11.2 months for all other patients. Additional predictors of improved survival on univariate analysis included ,3 BM, controlled or absent systemic disease, and controlled local disease. On multivariate analysis, only HER-2 status, number of BM, and local disease status remained independent predictors of survival. CONCLUSIONS HER-2 status is a strong predictor of survival after the diagnosis of BM. The survival of breast cancer patients with BM appears to be improving, but a better understanding of both the predictors of brain recurrence and the delayed effects of treatment is needed to properly counsel patients regarding the risk-benefit ratio of various treatment modalities. Cancer 2008. © 2008 American Cancer Society. [source] Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/neu in synovial sarcoma,CANCER, Issue 4 2005Dafydd G. Thomas M.D., Ph.D. Abstract BACKGROUND Synovial sarcomas are high-grade soft tissue neoplasms often characterized by a biphasic spindle and epithelioid cell morphology. The majority of synovial sarcomas harbor a specific chromosomal translocation in which the proximal portion of the SYT gene at chromosome 18q11 is fused to the distal portion of one of several duplicated SSX genes (most notably SSX1 and SSX2) at chromosome Xp11. SYT/SSX1 translocations are seen in nearly three times as many synovial sarcomas as SYT/SSX2 translocations. Although the SYT/SSX2 fusion is usually associated with the monophasic disease pattern, the SYT/SSX1 fusion is present in tumors with biphasic or monophasic patterns. The SYT/SSX1 fusion gene is associated with more aggressive tumor growth and poor outcome. Despite advances in the therapy of local disease, distant metastasis remains the predominant cause of death. Accordingly, there is a need for alternate therapies, such as those recently developed against the receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and HER-2/neu. METHODS Archival specimens of synovial sarcoma (n = 38) representing 30 patients were assessed for EGFR and HER-2/neu protein expression by standard immunohistochemical techniques. To validate the immunohistochemistry results, quantitative real-time polymerase chain reaction (Q-PCR) assays using either fresh and/or archival material was performed. The presence of gene amplification was determined by chromogenic in-situ hybridization. RESULTS EGFR and HER-2/neu protein were detected by immunohistochemistry in 21 of 38 (55.3%) and 20 of 38 (52.6%) synovial specimens, respectively. EGFR immunoreactivity showed a granular and membranous pattern, whereas HER-2/neu immunoreactivity demonstrated only a membrane pattern. Coexpression was observed in 13 of 38 specimens (34.2%). HER-2/neu expression by immunohistochemistry in synovial sarcomas was restricted to tumors with the SYT/SSX1 translocations. Of 6 specimens with SSX2 translocation, none (0%) showed HER-2/neu immunoreactivity and 1 (17%) demonstrated EGFR expression. Q-PCR demonstrated the presence of mRNA for EGFR and HER-2/neu in 19 of 30 specimens (63.3%) and 22 of 30 specimens (73.3%), respectively. EGFR and HER-2/neu were expressed at low concentrations compared with the expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). No evidence of gene amplification was observed. CONCLUSIONS EGFR and HER-2/neu are expressed in the majority of patients with SYT/SSX1 synovial sarcomas, albeit at low levels. Treatment with tyrosine kinase inhibitors may represent appropriate alternate therapy for these patients. Cancer 2005. © 2005 American Cancer Society. [source] |