Long-term Results of a Multicenter Randomized Phase III Trial of Induction Chemotherapy With Cisplatin, 5-fluorouracil, ± Docetaxel for Larynx Preservation.

BACKGROUND: The purpose of GORTEC 2000-01 was to compare the long-term efficacy and safety of induction chemotherapy with cisplatin (P) and 5-fluorouracil (F) with or without docetaxel (T) for larynx preservation. METHODS: Operable patients with untreated stage III or IV larynx or hypopharynx invasive squamous cell carcinoma who required total laryngectomy were randomly assigned to three cycles of induction chemotherapy with either TPF or PF, followed by radiation therapy for responders. The primary endpoint was three-year larynx preservation rate. Secondary endpoints included larynx dysfunction-free survival (LDFFS), overall survival (OS), disease-free survival (DFS), loco-regional control rate (LCR), cause of death, and later toxicity rates. Survival and other data were analyzed by Kaplan-Meier methods. All statistical tests were two-sided. RESULTS: Two hundred thirteen patients were treated with median follow-up of 105 months. The five- and 10-year larynx preservation rates were 74.0% (95% CI = 0.64 to 0.82) vs 58.1% (95% CI = 0.47 to 0.68) and 70.3% (95% CI = 0.58 to 0.8) vs 46.5% (95% CI = 0.31 to 0.63, P = .01) in the TPF vs PF arm, respectively. The five- and 10-year LDFFS rates were 67.2% (95% CI = 0.57 to 0.76) vs 46.5% (95% CI = 0.36 to 0.57) and 63.7% (95% CI = 0.52 to 0.74) vs 37.2% (95% CI = 0.24 to 0.52, P = .001), respectively. OS, DFS, and LCR were not statistically improved in the TPF vs the PF arm. Statistically fewer grade 3-4 late toxicities of the larynx occurred with the TPF regimen compared with the PF arm (9.3% vs 17.1%, G-test, P = .038). CONCLUSION: Long-term follow-up confirms that induction chemotherapy with TPF increased larynx preservation and larynx dysfunction-free survival. In this larynx preservation approach using induction chemotherapy, TPF should be recommended, followed by radiation therapy.

Effects of low-dose and high-dose postoperative radioiodine therapy on the clinical outcome in patients with small differentiated thyroid cancer having microscopic extrathyroidal extension.

BACKGROUND: It is unclear whether differentiated thyroid cancer (DTC) patients classified as intermediate risk based on the presence of microscopic extrathyroidal extension (ETE) should be treated with low or high doses of radioiodine (RAI) after surgery. We evaluated success rates and long-term clinical outcomes of patients with DTC of small tumor size, microscopic ETE, and no cervical lymph node (LN) metastasis treated either with a low (1.1 GBq) or high RAI dose (5.5 GBq). METHODS: This is a retrospective analysis of a historical cohort from 2000 to 2010 in a tertiary referral hospital. A total of 176 patients with small (≤2 cm) DTC, microscopic ETE, and no cervical LN metastasis were included. Ninety-six patients were treated with 1.1 GBq (LO group) and 80 patients with 5.5 GBq (HI group). Successful RAI therapy was defined as (i) negative stimulated thyroglobulin (Tg) in the absence of Tg antibodies, and (ii) absence of remnant thyroid tissue and of abnormal cervical LNs on ultrasonography. Clinical recurrence was defined as the reappearance of disease after ablation, which was confirmed by cytologically or pathologically proven malignant tissue or of distant metastatic lesions. RESULTS: There was no significant difference in the rate of successful RAI therapy between the LO and HI groups (p=0.75). In a subgroup analysis based on tumor size, success rates were not different between the LO group (34/35, 97%) and the HI group (50/56, 89%) in patients with a tumor size of 1-2 cm (p=0.24). In patients with smaller tumor size (≤1 cm), there was no significant difference in success rates between the LO (59/61, 97%) and HI groups (22/24, 92%; p=0.30). No patient had clinical recurrences in either group during the median 7.2 years of follow-up. CONCLUSIONS: Low-dose RAI therapy is sufficient to treat DTC patients classified as intermediate risk just by the presence of microscopic ETE.

Thyroid ablation with 1.1 GBq (30 mCi) iodine-131 in patients with papillary thyroid carcinoma at intermediate risk for recurrence.

BACKGROUND: Little is known about the medium- and long-term outcomes of thyroid ablation with 1.1 GBq (30 mCi) ¹³¹I in patients with papillary thyroid carcinoma who have a tumor >4 cm or accompanied by extrathyroid invasion or clinically detected lymph node metastases (cN1). The objective of this study was to evaluate the efficacy of ablation with 30 mCi ¹³¹I in this subgroup of patients and to report the medium-term outcomes. METHODS: We studied 152 patients with papillary thyroid carcinoma submitted to total thyroidectomy with apparently complete tumor resection, who had a tumor >4 cm or 2-4 cm accompanied by extrathyroid invasion or lymph node metastases, or ≤2 cm accompanied by both extrathyroid invasion and lymph node metastases. Patients with extensive extrathyroid invasion by the primary tumor were excluded. Lymph node involvement was detected by ultrasonography or palpation (cN1). RESULTS: Forty-two patients were prepared by administration of recombinant human thyrotropin and 110 by levothyroxine withdrawal. Posttherapy whole-body scanning revealed unequivocal ectopic uptake in three patients. When evaluated 9-12 months after ablation, 123 patients had achieved complete ablation (stimulated thyroglobulin [Tg] <1 ng/mL, negative anti-Tg antibodies, and neck ultrasonography); a new posttherapy whole-body scanning revealed persistent disease in 2 patients whose initial posttherapy whole-body scanning (obtained at the time of ablation) had already shown ectopic uptake; 12 patients presented with a Tg >1 ng/mL and 14 had positive anti-Tg antibodies without apparent metastases; 1 patient had metastases not detected at the time of ablation. Recurrence was observed in an additional 6 patients during follow-up (median 76 months). There was no case of death related to the disease. Therefore, an activity of 30 mCi failed in only 9 (6%) patients with persistent disease or recurrence after ablation. None of the variables analyzed (sex, age, tumor size, multicentricity, extrathyroid invasion, lymph node metastases, preparation [recombinant human thyrotropin or levothyroxine withdrawal]) was a predictor of ablation failure. CONCLUSIONS: An activity of 30 mCi ¹³¹I is effective in thyroid ablation in patients with stage T3 and/or N1 papillary thyroid carcinoma.

The results of selective use of radioactive iodine on survival and on recurrence in the management of papillary thyroid cancer, based on Memorial Sloan-Kettering Cancer Center risk group stratification.

BACKGROUND: The American Thyroid Association guidelines recommend the routine use of radioactive iodine for remnant ablation (RRA) in all T3 or greater primary tumors, and selective use in patients with intrathyroidal disease >1 cm, or evidence of nodal metastases. The guidelines recognize that there is conflicting and inadequate data to make firm recommendations for most patients. The aim of this study was to analyze our institutional experience of the use of RRA in the management of papillary thyroid cancer, with a particular focus on outcomes for those patients selected not to receive RRA. METHODS: We retrospectively reviewed 1129 consecutive patients who underwent total thyroidectomy at the Memorial Sloan-Kettering Cancer Center between 1986 and 2005. Of these, 490 were pT1-2 N0, 193 pT1-2 N1, and 444 pT3-4. Details on recurrence and disease-specific survival were recorded by the Kaplan-Meier method and compared using the log-rank test. RESULTS: The five-year disease-specific survival and recurrence-free survival in the pT1/T2 N0, pT1-2 N1, and pT3-4 were 100% and 92%, 100% and 92%, and 98% and 87% respectively. Low-risk patients who were managed without RRA (who tended to have limited primary disease, pT1-2, and low-volume metastatic disease in the neck, pT1-2 N1-fewer than five nodes, all <1 cm greatest dimension) had five-year recurrence-free survival of >97%. In the group with advanced local tumors (pT3-4), those patients who did not receive RRA (who tended to have pT3 N0 disease) had five-year recurrence-free survival of >90%. CONCLUSION: Following appropriate surgical management, the majority of patients with low-risk local disease and even some patients with more advanced-stage (pT3) tumors or regional metastases have low rates of recurrence and high rates of survival when managed without RRA.

Perioperative arginine-supplemented nutrition in malnourished patients with head and neck cancer improves long-term survival.

BACKGROUND: Plasma arginine concentrations are lower in patients with cancer, which indicates that arginine metabolism may be disturbed in these patients. Arginine supplementation has been associated with positive effects on antitumor mechanisms and has been shown to reduce tumor growth and to prolong survival. Furthermore, the prognosis of patients with head and neck cancer remains disappointing. Insufficient intake frequently leads to malnutrition, which contributes to high morbidity and mortality rates. OBJECTIVE: The aim of this study was to assess the long-term effects of perioperative arginine supplementation in severely malnourished patients with head and neck cancer. DESIGN: In this double-blind, randomized, controlled trial, we randomly assigned 32 severely malnourished patients with head and neck cancer to receive 1) standard perioperative enteral nutrition (n = 15) or 2) arginine-supplemented perioperative enteral nutrition (n = 17). The primary outcome was long-term (≥10 y) survival. Secondary outcomes included the long-term appearance of locoregional recurrence, distant metastases, and second primary tumors. RESULTS: No significant differences in baseline characteristics were observed between groups. The group receiving arginine-enriched nutrition had a significantly better overall survival (P = 0.019) and better disease-specific survival (P = 0.022). Furthermore, the arginine-supplemented group had a significantly better locoregional recurrence-free survival (P = 0.027). No significant difference in the occurrence of distant metastases or occurrence of a second primary tumor was observed between the groups. CONCLUSION: Perioperative arginine-enriched enteral nutrition significantly improved the long-term overall survival and long-term disease-specific survival in malnourished patients with head and neck cancer.

Chemoradiotherapy for locally advanced head and neck cancer: 10-year follow-up of the UK Head and Neck (UKHAN1) trial.

BACKGROUND: Between 1990 and 2000, we examined the effect of timing of non-platinum chemotherapy when combined with radiotherapy. We aimed to determine whether giving chemotherapy concurrently with radiotherapy or as maintenance therapy, or both, affected clinical outcome. Here we report survival and recurrence after 10 years of follow-up. METHODS: Between Jan 15, 1990, and June 20, 2000, 966 patients were recruited from 34 centres in the UK and two centres from Malta and Turkey. Patients with locally advanced head and neck cancer, and who had not previously undergone surgery, were randomly assigned to one of four groups in a 3:2:2:2 ratio, stratified by centre and chemotherapy regimen: radical radiotherapy alone (n=233); radiotherapy with two courses of chemotherapy given simultaneously on days 1 and 14 of radiotherapy (SIM alone; n=166); or 14 and 28 days after completing radiotherapy (SUB alone, n=160); or both (SIM+SUB; n=154). Chemotherapy was either methotrexate alone, or vincristine, bleomycin, methotrexate, and fluorouracil. Patients who had previously undergone radical surgery to remove their tumour were only randomised to radiotherapy alone (n=135) or SIM alone (n=118), in a 3:2 ratio. The primary endpoints were overall survival (from randomisation), and event-free survival (EFS; recurrence, new tumour, or death; whichever occurred first) among patients who were disease-free 6 months after randomisation. Analyses were by intention to treat. This trial is registered at www.Clinicaltrials.gov, number NCT00002476. FINDINGS: All 966 patients were included in the analyses. Among patients who did not undergo surgery, the median overall survival was 2.6 years (99% CI 1.9-4.2) in the radiotherapy alone group, 4.7 (2.6-7.8) years in the SIM alone group, 2.3 (1.6-3.5) years in the SUB alone group, and 2.7 (1.6-4.7) years in the SIM+SUB group (p=0.10). The corresponding median EFS were 1.0 (0.7-1.4), 2.2 (1.1-6.0), 1.0 (0.6-1.5), and 1.0 (0.6-2.0) years (p=0.005), respectively. For every 100 patients given SIM alone, there are 11 fewer EFS events (99% CI 1-21), compared with 100 given radiotherapy, 10 years after treatment. Among the patients who had previously undergone surgery, median overall survival was 5.0 (99% CI 1.8-8.0) and 4.6 (2.2-7.6) years in the radiotherapy alone and SIM alone groups (p=0.70), respectively, with corresponding median EFS of 3.7 (99% CI 1.1-5.9) and 3.0 (1.2-5.6) years (p=0.85), respectively. The percentage of patients who had a significant toxicity during treatment were: 11% (radiotherapy alone, n=25), 28% (SIM alone, n=47), 12% (SUB alone, n=19), and 36% (SIM+SUB, n=55) among patients without previous surgery; and 9% (radiotherapy alone, n=12) and 20% (SIM alone, n=24) among those who had undergone previous surgery. The most common toxicity during treatment was mucositis. The percentage of patients who had a significant toxicity at least 6 months after randomisation were: 6% (radiotherapy alone, n=13), 6% (SIM alone, n=10), 4% (SUB alone, n=7), and 6% (SIM+SUB, n=9) among patients who had no previous surgery; and 7% (radiotherapy alone, n=10) and 11% (SIM alone, n=13) among those who had undergone previous surgery. The most common toxicity 6 months after treatment was xerostomia, but this occurred in 3% or less of patients in each group. INTERPRETATION: Concurrent non-platinum chemoradiotherapy reduces recurrences, new tumours, and deaths in patients who have not undergone previous surgery, even 10 years after starting treatment. Chemotherapy given after radiotherapy (with or without concurrent chemotherapy) is ineffective. Patients who have undergone previous surgery for head and neck cancer do not benefit from non-platinum chemotherapy. FUNDING: Cancer Research UK, with support from University College London and University College London Hospital Comprehensive Biomedical Research Centre.

[Abscopal effect on metastatic tumor induced by oncolytic virus of H101 combining with local heating].

BACKGROUND & OBJECTIVE: The abscopal effect on the tumors is a distant antitumor activity induced by local treatments. The study was to observe the induction of abscopal effect by the combination of H101 oncolytic virotherapy with local heating. METHODS: Five patients with histologically confirmed, surgically unresectable metastatic malignant tumors (2 nasopharyngeal carcinomas, 1 pulmonary carcinoma, 1 parosteal sarcoma and 1 bladder carcinoma) that had definitely failed to the conventional chemotherapy and radiotherapy or refused these therapies were enrolled in this experimental therapy. All patients were treated with local intra tumor injection of H101 (5x10(11) - 15x10(11) VP) combined with 60-min heating at 42 degrees C. RESULTS: Two patients were cured with complete regressions of both injected and non-injected tumors and have survived for a long period up to date. Three patients responded to the novel therapy variously and eventually died from the disease, who survived 29, 15 and 13 months, respectively. CONCLUSION: The abscopal antitumor effect could be induced by the combination of H101 local intratumoral injection with heating.

Management of cervical metastases in advanced squamous cell carcinoma of the tonsillar fossa following radiotherapy.

OBJECTIVE: To assess the value of planned neck dissection in patients with a complete response to definitive radiotherapy for squamous cell carcinoma of the tonsillar fossa with advanced nodal disease. DESIGN: Case series. SETTING: Academic tertiary care medical center. PATIENTS: A consecutive series of 36 patients with squamous cell carcinoma of the tonsillar fossa with N2 or N3 nodal disease treated with primary radiation therapy with or without concurrent chemotherapy between January 1, 1992, and April 1, 2003, at the University of California, San Francisco, Comprehensive Cancer Center. Patients treated with primary surgery, those treated with palliative intent, or those with preexisting malignancies were excluded. MAIN OUTCOME MEASURES: Regional control and overall survival. RESULTS: Of the study group, 15 patients (42%) achieved a complete response, 17 (47%) achieved a partial response, and 1 (3%) was a nonresponder. The response in 3 patients (8%) could not be assessed. Of the 15 patients with a complete response, only 2 (13%) later developed regional recurrences, 1 of which was an isolated recurrence in the neck. Regional control and overall survival at 3 years were 78% and 48%, respectively. CONCLUSIONS: The rate of regional recurrence after a complete response to radiation therapy with or without concurrent chemotherapy for tonsillar squamous cell carcinoma with advanced cervical metastases is low. Our results support close surveillance of the neck in those who have achieved a complete response after radiation therapy with or without chemotherapy.

CUP (carcinoma of unknown primary) syndrome in head and neck: clinic, diagnostic, and therapy.

BACKGROUND: Up to 10% of all cervical lymph node metastases present without a known primary site. Between 70 and 80% of the found primary tumors are located in the head and neck region, because cervical lymph nodes represent the lymph drainage of the head and neck. PATIENTS AND METHODS: We demonstrate the clinic, diagnostic management and therapy of carcinoma of unknown primary (CUP) in this retrospective study of 75 patients who primarily presented cervical metastases with unknown primary tumor at the Otorhinolaryngological Department of the University of Leipzig, Germany. RESULTS: A primary tumor was found in 44% of the patients, and 76% of the primary tumors were localized in the head and neck region. The overall 5-year survival rate was 13.3%. The 34 patients with pretherapeutically detected primary tumors showed a tendency towards better survival, with a 5-year survival rate of 21% compared to 10% in patients with undetected primary. CONCLUSIONS: Following a thorough physical examination, radiologic imaging, i.e., computed tomography and/or magnetic resonance imaging, of the head and neck region as well a chest X ray, panendoscopy with biopsy of the most probable tumor sites, and diagnostic tonsillectomy should be performed. Further diagnostic procedures as gastroenterologic, urogenital and gynecological examinations should be performed, depending on histology and location of the node and under consideration of cost-benefit analysis. Curative treatment should at least include ipsilateral neck dissection and adjuvant irradiation of the complete cervical lymph drainage. In the literature, radiation of the laryngopharyngeal mucosa is still discussed controversially: some authors recommend the irradation of the pharyngeal mucosa extending from the nasopharynx to the upper esophagus, whereas others regard the resulting side effects as too high compared to the expected benefit.

Comparison of (18)F-FDG, (131)I-Na, and (201)Tl in diagnosis of recurrent or metastatic thyroid carcinoma.

UNLABELLED: There are several reports about the usefulness of (18)F-FDG PET in thyroid cancer. However, few studies have compared FDG PET with (131)I and (201)Tl scintigraphy. The aim of this study was to evaluate the clinical significance of whole-body FDG PET in differentiated thyroid cancer and to compare the results with those obtained from (131)I and (201)Tl scintigraphy. METHODS: Whole-body FDG PET was performed on 32 patients (10 men, 22 women; age range, 30-77 y; mean age, 54 y) with differentiated thyroid cancer (5 cases of follicular cancer and 27 of papillary cancer) after total thyroidectomy. An overall clinical evaluation was performed, including cytology, thyroglobulin level, sonography, MRI, and CT, to allow a comparison with functional imaging results for each patient. Metastatic regions were divided into five areas: neck, lung, mediastinum, bone, and other. Multiple lesions in one area were defined as one lesion. The tumor-to-background ratio (TBR) was measured for the lesions that were positive for both (201)Tl uptake and FDG PET uptake. RESULTS: The number of lesions totaled 47. Forty-one (87%) were detected by all scintigraphic methods. FDG uptake was concordant with (131)I uptake in only 18 lesions (38%). FDG uptake was concordant with (201)Tl uptake in 44 lesions (94%). Only one lesion was negative for FDG uptake and positive for (201)Tl uptake, and two lesions were positive for FDG uptake and negative for (201)Tl uptake. A significant correlation was seen between the TBR of (201)Tl and that of FDG (r = 0.69; P<0.05). CONCLUSION: These data indicate that for detecting metastatic lesions, FDG PET and (131)I scintigraphy may provide complementary information, whereas FDG PET may provide results similar to those of (201)Tl scintigraphy. Thus, the combination of (131)I scintigraphy and FDG PET (or (201)Tl scintigraphy) is the method of choice for detecting metastatic thyroid cancer after total thyroidectomy.

Percutaneous dilatational tracheostomy in a patient with thyroid cancer and severe airway obstruction.

A patient with extensive metastatic thyroid cancer scheduled for palliative tracheostomy is presented. He had laryngeal dislocation with severe airway obstruction and few anatomical landmarks due to tumour infiltration and radiation. Successful percutaneous dilatational tracheostomy was performed under local anaesthesia.

The usefulness of iodine-123 whole-body scans in evaluating thyroid carcinoma and metastases.

OBJECTIVE: It is recognized that diagnostic doses of (131)I larger than 3 mCi will cause some cell injury to the tissue in which it concentrates and reduce subsequent uptake of (131)I administered therapeutically. Iodine-123 has been suggested as an alternate radiopharmaceutical to perform whole-body scans since its primary emissions are photons with minimal particulate radiation and it does not cause thyroid stunning and cell injury. The purpose of this study was to assess the effectiveness of (123)I for whole-body scans. METHODS: We examined 12 patients who had (123)I whole-body scans for known papillary/follicular thyroid cancer and 1 patient with Hurthle cell carcinoma, all with suspected metastases. All patients had undergone neck surgery and were given 0.81-0 mCi (123)I. Twenty-four hours later a whole-body image and static views of relevant areas were obtained. If abnormal uptake was noted, patients were treated with large doses of (131)I and then had whole-body (131)I scans 7-10 d post-therapy. These images were compared to (123)I whole-body scans. RESULTS: All 13 patients had abnormal (123)I scans and were treated with therapeutic doses of (123)I, followed by whole-body scans 7-10 d later. In 11 patients the activity seen on the 123I scans correlated well with that seen on (131)I scans. In 1 patient, additional lesions were noted on the (131)I images. In another patient, neck activity was seen on the (123)I scan but not on the subsequent (131)I post-therapy scan. The (123)I activity was felt to represent esophageal lumen activity. CONCLUSION: We found (123)1 effective in demonstrating residual thyroid tissue, thyroid carcinoma and metastases, and recommend its use for whole-body iodine scans since it does not cause thyroid stunning.

Surgical treatment for carcinoma of the thoracic esophagus with major involvement in the neck or upper mediastinum.

BACKGROUND AND OBJECTIVES: In carcinoma of the thoracic esophagus, most surgeons consider that esophagectomy is contraindicated in patients with clinical evidence of major extraesophageal involvement in the lower neck or peritracheal regions. However, metastases to these regions are commonly found even in early phases of carcinoma invasion. With recent progress in preoperative assessment, operative technique and adjuvant therapy, esophagectomy could possibly benefit appropriately selected patients. METHODS: We retrospectively analyzed results in 42 patients who had major involvement in the neck or upper mediastinum and who underwent esophagectomy with systematic lymph node dissection. We operated upon patients unless lesions were assessed as definitely unresectable. Preoperatively, 32 had enlarged peritracheal nodes greater than 15 mm in diameter on computed tomography, 18 had hard unmobile tumors in the lower neck, 9 had recurrent laryngeal nerve palsy, and 10 had findings suggestive of tracheal invasion. Preoperative radiotherapy and/or chemotherapy was given to 32 low-risk patients. RESULTS: The hospital mortality rate was 4%. Bowel reconstruction was completed in all cases. No macroscopically recognizable lesion remained after operation in 35 patients. Eight patients were alive 5 years after esophagectomy, including 2 who had had tracheal invasion and 1 with recurrent nerve palsy. The cumulative 5-year survival was 38%. CONCLUSIONS: Evidence of major involvement of the neck and/or upper mediastinum does not always contraindicate resection. Aggressive esophagectomy combined with perioperative adjuvant therapy yielded acceptable palliation and occasional cure in cases with technically resectable lesions.

Diagnostic value of technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI) scintigraphy in detecting thyroid cancer metastases: a critical evaluation.

Technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI) scintigraphy has recently been used in clinical application for detecting thyroid cancer metastases, its role being considered supplementary to serum thyroglobulin (Tg) measurements and radioactive iodine (131I) whole-body scans (WBS). The present retrospective study was designed to elucidate the role of 99mTc-MIBI scans in localizing metastatic lesions by assessing sensitivity and specificity of the scan results obtained in a group of 68 thyroidectomized thyroid cancer patients. Presence or absence of thyroid cancer was judged with other diagnostic modes including serum Tg measurements, 131I WBS, bone scans, chest x-rays, computed tomography (CT), ultrasonography, histopathology, and evolution of disease during follow-up. All scans were read on lesion basis for detecting neck, lung, and bone metastases and also on region basis, namely head-neck, chest, and abdomen-pelvis-extremities (ab-p-ex) areas. The sensitivity of detection was 94.4% (17/18) for neck, 78.4% (40/51) for lung, and 92.8% (64/69) for skeletal lesions. Positive predictive value (PPV) and negative predictive value (NPV) were 96.3% (26/27) and 97.7% (43/44) for head-neck; 94.7% (71/75) and 50.0% (12/24) for chest; 100.0% (25/25) and 93.1% (54/58) for ab-p-ex regions, respectively. For all scan sites taken together, PPV and NPV were 96.1% (122/127) and 86.5% (109/126), respectively. In conclusion, the present study reveals that 99mTc-MIBI can be proposed as a first-line diagnostic agent for the follow-up protocol of thyroid cancer patients, although the ability to detect small lung metastases is somewhat limited.

Interleukins and contrasuppression induce immune regression of head and neck cancer.

Metastatic squamous cell head and neck cancer was treated in four patients with low-dose cyclophosphamide (to reduce suppressor T-cell activity), indomethacin (to reduce prostaglandins that mediate macrophage-induced immune suppression), zinc (to augment T-cell function via thymulin), and mixed natural interleukins perilymphatically in the neck (as adjuvant for tumor antigen in the region). Three patients responded within 7 days with major tumor regressions progressive during the period of treatment and associated with increased infiltration with lymphocytes and tumor cell lysis. Two showed histologic features of intense delayed hypersensitivity with granulomatous changes. The fourth patient was anergic and failed to respond clinically. Tumor-specific immune response, despite preexisting immunodeficiency, is postulated as the mechanism of the responses in these patients.

Prognostic factors and management considerations in patients with cervical metastases of thyroid cancer.

Included among the controversies involving thyroid cancer are the risk factors and treatment decisions in patients with nodal metastases. We have reviewed selected clinical, pathologic, and therapeutic parameters in patients who present with cervical node metastases and related these parameters to disease outcome. There were 108 patients (68 women, 40 men), who had a mean age of 54 years. Univariate analysis showed a significantly increased risk of recurrence to be associated with the presence of primary tumor invasion (vascular, lymphatic, nerve, or muscle), the age and sex of the patient, the presence of mediastinal nodes, and adjuvant treatment with iodine 131. The presence of tumor invasion, the age and sex of the patient, and the presence of mediastinal nodes were significantly associated with higher rates of recurrence when tested by multivariate analysis. The 5- and 10-year disease-free survival rates were 76% and 72%, respectively, with a mean follow-up of 86 months. A comparison of recurrence and survival rates in thyroid cancer patients who were either node positive or node negative during the same 10-year period (152 patients) showed no statistically significant differences. However, node-positive patients with the risk factors of tumor invasion, age over 45 years, and positive mediastinal nodes had more aggressive disease. Although thyroid cancer patients with nodal metastases generally have a good prognosis, high-risk subgroups have been identified who may benefit from a more aggressive therapeutic and follow-up approach.

Metastatic head and neck malignancy treated using MRI guided interstitial laser phototherapy: an initial case report.

Interstitial laser phototherapy (ILP) guided by magnetic resonance imaging (MRI) may become an attractive adjunctive modality for the treatment of deep and surgically inaccessible tumors of the head and neck when accurate methods of laser dosimetry and "real-time" monitoring techniques with the MRI are introduced. We recently demonstrated in ex vivo and in vivo models, a linear relationship between levels of laser energies, thermal profiles, MR signal intensity changes, and histopathological tissue damage. Results of treatment in a patient with an unresectable large right jugulodigastric metastatic squamous carcinoma using new approach of MRI guided ILP are now reported. The patient complained of significant right-sided neck pain and headaches secondary to a rapidly growing metastatic lymphadenopathy which recurred after previous surgery, radiation, and chemotherapy. Two treatment sessions were used at an interval of 2 weeks. Each treatment was performed in the MRI suite under heavy sedation. Using a 600-microns bare fiber of the Nd:YAG laser implanted interstitially under MR guidance, the metastatic node was treated at three sites. T1- and T2-weighted images were performed prior to, immediately after, 24 and 48 hours, and 4, 5, 7, 9, 16, and 25 days post-treatment. Successful relief of pain and growth arrest of this node was observed after the second treatment and at the 3-month follow-up. These results demonstrate that this technique of ILP guided by MRI may be feasible in humans, and will become clinically practical when appropriate methods of dosimetry and instrumentation are developed.

The modification of specific absorption rates in interstitial microwave hyperthermia via tissue-equivalent material bolus.

Patterns of specific absorption rates generated by interstitial, microwave antenna arrays must be experimentally ascertained and quantified to facilitate their clinical incorporation. Phantom studies involved the use of four single-gap, coaxial antennas oriented in a 2 cm square array. These dipoles were driven in phase by a microwave generator at a frequency of 915 MHz. The inherent limitations in modifying the specific absorption rate patterns were addressed with the addition of bolus to the phantom. These additions of Guy's muscle tissue-equivalent material were made either proximal or distal to the phantom proper. Experiments conducted in the presence and absence of tissue-equivalent material bolus showed the ability to achieve broader bands of 50% power deposition in certain bolus conditions. These heating patterns were sufficiently reproducible and predictable to warrant clinical application of the bolus addition. A through-and-through method of catheter implantation allowed for bolus addition when deemed necessary. Treatments with veterinary and human patients using the bolus method to modify heating patterns yielded augmented patterns of power deposition. The effective length of the antennas that would radiate efficiently was essentially broadened via introduction of a microwave-interacting medium. As a result of the tissue equivalent material's ability to absorb microwave power, it was necessary to interpose minimally-interactive styrofoam spacers to limit heat transfer effects at the tissue-bolus interfaces.