Precisely defining high-risk operable head and neck tumors based on RTOG #85-03 and #88-24: targets for postoperative radiochemotherapy?

OBJECTIVE: In the German physician-based emergency medical system (EMS) psychiatric emergency situations (PES) rank on third place contradictory to it's importance during emergency physician training program. The aim of our study was to examine the relevance of PES and the stress which PES imposes upon EMS physicians. Further, the interest of training programs on that issue was determined. Knowledge about PES was investigated by a short test. METHODS: 952 emergency physicians were sent a questionnaire about following: demographic data, frequency of PES, strain by PES, own knowledge, interest about training programs. Further five typical PES were presented for diagnostic and therapeutic judgement. RESULTS: 222 responded (183 men/37 women/2 without gender data, average age: 40.1 +/- 6.7, qualification as emergency physician: 9.6 +/- 5.1 years, most frequent subspeciality in-hospital physicians: anaesthesiology 67.5%, in-practice physicians: general medicine 72.1%). PES frequence was estimated at 9.4%, personal knowledge judged only by 13% as sufficient, 14.2 felt incapable by PES. 73% saw importance of training, especially expressed by the more experienced (P < 0.05). Test presented 65% correct diagnoses, 33% correct therapy, 26% incorrect decision of hospital admission. CONCLUSION: PES are a frequent problem of pre-hospital patient care for emergency physicians. As personal knowledge was estimated to be insufficient, the interest for courses concerning PES issues is high.     

Phase II trial of vindesine in advanced head and neck cancer

Twenty-one patients with advanced epidermoid carcinoma of the head and neck region were treated with vindesine. Therapy was started at a dose of 3 mg/m2. Dose escalation by 0.5 mg/m2 weekly to a maximum of 4.0 mg/m2 was permitted when no toxicity was seen. Major dose-limiting toxic effects were neutropenia and peripheral neuropathy. Objective responses were seen in five patients: three partial responses lasting 2, 2, and 3 months, and two minor responses lasting 2 and 5 months.     

Postoperative radiotherapy with concurrent cisplatin appears to improve locoregional control of advanced, resectable head and neck cancers: RTOG 88-24

PURPOSE: Despite aggressive surgery and postoperative radiation therapy, only 30% of patients who have advanced, potentially resectable carcinomas of the head and neck survive for 5 years. In the hope of improving this situation we studied the effect of postoperative radiotherapy delivered concurrently with cisplatin. METHODS AND MATERIALS: Patients who had Stage IV tumors and/or involved surgical margins received 60 Gy in 30 fractions over 6 weeks plus 100 mg/m2 of cisplatin on radiotherapy days 1, 23 and 43. Fifty-two patients participated in this trial and 51 were evaluated. Forty-three (84%) patients had pathologic T3 or T4 disease, 43 (84%) had Stage IV disease, and 27 (53%) had histologically involved surgical margins. RESULTS: Severe and life-threatening toxicities occurred in 20% and 12% of patients, respectively; the most common drug-related toxicities were leukopenia, anemia, nausea, and vomiting. Seventeen patients (43%) remain alive with no evidence of disease. Four patients (8%) died with no evidence of neoplastic disease, and one patient has died of a second independent malignancy. By actuarial analysis at 3 years, 48% of patients are alive, 81% have locoregional control of disease, and 57% are free of distant metastases. CONCLUSIONS: Based on comparison with similar patients treated in a prior Radiation Therapy Oncology Group/Intergroup trial (RTOG), we conclude that postoperative radiotherapy with concurrent cisplatin may improve locoregional control rates and should be prospectively tested.     

Radiation dose perturbation at tissue-titanium dental interfaces in head and neck cancer patients

PURPOSE: To determine the dose perturbation effects at the tissue-metal implant interfaces in head and neck cancer patients treated with 6 MV and 10 MV photon beams. METHODS AND MATERIALS: Phantom measurements were performed to investigate the magnitude of dose perturbation to the tissue adjacent to the titanium alloy implants with (100 mu and 500 mu thick) and without hydroxylapatite (HA) coating. Radiographic and radiochromic films were placed at the upper (and lower) surface of circular metal discs (diameter x thickness: 15 x 3.2, 48 x 3.2, 48 x 3.8 mm2) in a solid water phantom and were exposed perpendicular to radiation beams. The dosimeters were scanned with automatic film scanners. Using a thin-window parallel-plate ion chamber, dose perturbation were measured for a 48 x 3.2 mm2 disc. RESULTS: At the upper surface of the tissue-dental implant interface, the radiographic data indicate that for 15 x 3.2 mm2 uncoated, as well as 100 mu coated discs, dose perturbation is about +22.5% and +20.0% using 6 MV and 10 MV photon beams, respectively. For 48 x 3.2 mm2 discs, these values basically remain the same. However, for 48 x 3.8 mm2 discs, these values increase slightly to about +23.0% and +20.5% for 6 MV and 10 MV beams, respectively. For 48 x 3.2 mm2 discs with 500 mu coating, dose enhancement is slightly lower than that obtained for uncoated and 100 mu coated discs for each beam energy studied. At the lower interface for 15 x 3.2 mm2 and 48 x 3.2 mm2 uncoated and 100 mu coated discs, dose reduction is similar and is about -13.5% and -9.5% for 6 MV and 10 MV beams, respectively. For 48 x 3.8 mm2 discs, dose reduction is about -14.5% and -10.0% for 6 MV and 10 MV beams, respectively. For 48 x 3.2 mm2 discs with 500 mu coating, the dose reduction were slightly higher than those for uncoated and 100 mu coated discs. CONCLUSIONS: For the beam energies studied, dose enhancement is slightly larger for the lower energy beam. The results of dose perturbation were similar for 100 mu coated and uncoated discs. These results were slightly lower for the 500 mu coated discs but are not clinically significant. The dosimetry results obtained from radiochromic films were similar to the ones obtained from radiographic film. The dose enhancement results obtained from ion chamber dosimetry are higher than those obtained from film dosimetry. The ion chamber data represent the data at "true" tissue-titanium interface, whereas the ones obtained from film dosimetry represent the data at film-titanium interface.     

Phase II trial of cisplatin and gemcitabine in advanced squamous-cell carcinoma of the head and neck

BACKGROUND: To evaluate the toxicity profile and efficacy of cisplatin combined with gemcitabine in patients with irresectable locally recurrent or metastatic squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Gemcitabine was given at a dose of 800 mg/m2 on days 1, 8 and 15, plus cisplatin at a dose of 50 mg/m2 on days 1 and 8; every four weeks. RESULTS: Twenty-four patients with a median age of 59 years (range 42-74) were included. All patients were evaluable for toxicity and 22 patients were assessable for response. Eleven cases had advanced recurrent locoregional disease while 13 patients had metastatic disease. One CR (4.7%) and four PR (18%) were observed, for an overall response rate of 22.7% (95% CI: 8%-42%). The main toxicity was hematological: neutropenia grade 3-4 in 28% of the cycles and thrombocytopenia grade 3-4 in 16%. The most significant non-hematological toxicity was asthenia grade 2-3 in 24% of the cycles. CONCLUSIONS: This cisplatin plus gemcitabine combination schedule has a favourable toxicity profile with a discrete activity in patients with locally recurrent or metastatic squamous-cell carcinoma of the head and neck.     

Pharmacokinetic re-evaluation and phase I study of high dose epirubicin in advanced non-small cell lung cancer

We performed a phase I trial to evaluate the toxicity and the maximum tolerated dose of high dose epirubicin on a three-consecutive-day schedule on Japanese patients with advanced non-small cell lung cancer. Fourteen patients were entered in the study. At least three patients were assigned to each different dose level. Epirubicin was given intravenously daily for three day by bolus injection. The dose was started at 60 mg/m2/course and escalated by 30 mg/m2/course. Granulocytopenia was found to be the dose limiting toxicity with a maximum tolerated dose of 150 mg/m2/course. Thrombocytopenia and non-hematological toxicities were mild and well tolerated. The maximum tolerated dose was lower than that in Europe and Canada. Partial responses were observed in two out of five patients on 150 mg/m2/course. The recommended phase II dose for high dose epirubicin was demonstrated to be 120 mg/m2/course. A further dose-escalating study of epirubicin in conjunction with the administration of granulocyte colony stimulating factor is scheduled for the determination of its antitumor activity in non-small cell lung cancer.     

5-Fluorouracil dose intensification and granulocyte-macrophage colony-stimulating factor in cisplatin-based chemotherapy for relapsed squamous cell carcinoma of the head and neck: a phase II study

We reviewed the clinical record of all patients admitted to Saga Medical School Hospital during the most recent 10 years and found that 17 (0.03%) were diagnosed as having necrotizing fasciitis. Bacteriological examination demonstrated that Vibrio vulnificus was the pathogen responsible in five patients (29%). The disease caused by V. vulnificus occurred in the warmer half of the year. All of the patients had underlying chronic liver dysfunction, and three of them had previously consumed raw seafood. In these patients, the predominant skin lesions were oedema and subcutaneous bleeding, such as ecchymosis and purpura, while superficial necrosis was not recognized. Three patients died of systemic complications. By contrast, all of the five patients with necrotizing fasciitis caused by Streptococcus pyogenes had the disorder in winter, and only one of them had chronic liver dysfunction. In skin lesions, subcutaneous bleeding was rare but necrosis was seen often. Despite the high incidence of systemic complications, no patients with streptococcal necrotizing fasciitis died. These findings suggest that the clinical features of necrotizing fasciitis caused by V. vulnificus are different from those of necrotizing fasciitis caused by classical pathogens, and that the two should be differentiated as early as possible to improve the prognosis.     

Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer

BACKGROUND: Regionally advanced, surgically unresectable non-small-cell lung cancer represents a disease with an extremely poor prognosis. External-beam irradiation to the primary tumor and regional lymphatics is generally accepted as standard therapy. The use of more aggressive radiation regimens and the addition of cytotoxic chemotherapy to radiotherapy have yielded conflicting results. Recently, however, results from clinical trials using innovative irradiation delivery techniques or chemotherapy before irradiation have indicated that patients treated with protocols that incorporate these modifications may have higher survival rates than patients receiving standard radiation therapy. PURPOSE: On the basis of these results, the Radiation Therapy Oncology Group (RTOG)-Eastern Cooperative Oncology Group (ECOG) elected to conduct a phase III trial comparing the following regimens: 1) standard radiation therapy, 2) induction chemotherapy followed by standard radiation therapy, and 3) twice-daily radiation therapy. METHODS: Patients with surgically unresectable stage II, IIIA, or IIIB non-small-cell lung cancer were potential candidates. Staging was nonsurgical. Patients were required to have a Karnofsky performance status of 70 or more and weight loss less than 5% for 3 months prior to entry into the trial, to be older than 18 years of age, and to have no metastatic disease. Of the 490 patients registered in the trial, 452 were eligible. The disease in 95% of the patients was stage IIIA or IIIB. More than two thirds of the patients had a Karnofsky performance status of more than 80. Patients were randomly assigned to receive either 60 Gy of radiation therapy delivered at 2 Gy per fraction, 5 days a week, over a 6-week period (standard radiation therapy); induction chemotherapy consisting of cisplatin (100 mg/m2) on days 1 and 29 and 5 mg/m2 vinblastine per week for 5 consecutive weeks beginning on day 1 with cisplatin, followed by standard radiation therapy starting on day 50; or 69.6 Gy delivered at 1.2 Gy per fraction twice daily (hyperfractionated radiation therapy). RESULTS: Toxicity was acceptable, with four treatment-related deaths. Three patients subsequently died of chronic pulmonary complications. Compliance with protocol treatment was acceptable. One-year survival (%) and median survival (months) were as follows: standard radiation therapy--46%, 11.4 months; chemotherapy plus radiotherapy--60%, 13.8 months; and hyperfractionated radiation therapy--51%, 12.3 months. The chemotherapy plus radiotherapy arm was statistically superior to the other two treatment arms (logrank P = .03). CONCLUSIONS: In "good-risk" patients with surgically unresectable non-small-cell lung cancer, induction chemotherapy followed by irradiation was superior to hyperfractionated radiation therapy or standard radiation therapy alone, yielding a statistically significant short-term survival advantage.     

Plasmacytomas of the head and neck

Plasmacytomas are rare tumors that often appear in the head and neck region and are characterized by a monoclonal proliferation of plasma cells. On both clinical presentation and pathologic examination these tumors may be confused with more common tumors of the head and neck. The purpose of this article is to review our experience with these rare neoplasms, with emphasis on clinical, pathologic, and therapeutic features. On retrospective chart review, we identified 20 patients with the diagnosis of plasmacytoma of the head and neck region at the Cleveland Clinic Foundation between 1976 and 1993. Records were reviewed with regard to initial symptoms, location of the neoplasm, diagnostic evaluation, treatment modalities, and survival. Of the 20 cases we identified, the tumor arose in the sinonasal/nasopharyngeal region in 11 (55%). Two cases (10%) represented medullary plasmacytomas, arising in the clavicle and presenting as supraclavicular masses. The mean follow-up was 60.2 months (range 6 to 131 months). In 15 of the 20 cases, immunohistochemistry staining for immunoglobulin light chain production was conducted. One of the two cases (50%) classified as medullary plasmacytoma demonstrated conversion to multiple myeloma, whereas only 2 of 18 cases of extramedullary plasmacytoma (11%) converted to multiple myeloma. The primary modality of treatment was radiation therapy with typical doses of 4500 to 6000 cGy. Kaplan-Meier survival estimates demonstrated 95% survival at 1 year, 82% survival at 5 years, and 10-year estimated survival of 72%. Plasmacytomas of the head and neck region are rare and on initial evaluation must be distinguished from multiple myeloma. The diagnostic evaluation includes appropriate radiologic and pathologic studies including immunohistochemistry. Despite the typical presentation as a locally destructive tumor, plasmacytomas are highly radiosensitive, and 70% to 80% survival may be obtained with the use of radiotherapy. Patients with plasmacytomas require long-term follow-up to detect conversion to multiple myeloma.     

Reconstruction of the head and neck

The collaboration of surgeons, radiation oncologists, chemotherapists, dentists, oral surgeons, prosthodontists, and speech therapists has led to major advances in the management of the difficult cancers of the head and neck area. The advent of myocutaneous flaps and the facilitation of microsurgical free flaps have ushered in an era of one-stage reconstructions to shorten the hospital stay and improve the overall therapeutic, functional, and cosmetic results.     

Melanomas of the head and neck

Melanomas of the skin and mucous membranes of the head and neck region are an uncommon problem for most clinicians. The article emphasizes the differences in terms of biological aggressiveness and treatment between lentigo maligna (LM) and lentigo maligna melanoma (LMM), superficial spreading melanoma (SSM), and nodular melanoma de novo. The results of radiotherapy in the treatment of melanoma of the head and neck are reviewed, and indications are suggested for the use of irradiation in the management of patients with this tumor. A brief discussion of the results of treatment of mucosal melanomas is given.     

Clinical impact of pharmacokinetically-guided dose adaptation of 5-fluorouracil: results from a multicentric randomized trial in patients with locally advanced head and neck carcinomas

A significant link between 5-fluorouracil (5FU) plasma concentration and its therapeutic activity has been demonstrated in colon and head and neck cancer patients for 5FU used as a continuous infusion. Dose adjustment based on pharmacokinetic follow-up has been proposed to decrease hematological and digestive toxicities, but the clinical impact of this approach has not yet been demonstrated. A randomized multicentric study was conducted to evaluate the clinical interest of 5FU dose adaptation guided by pharmacokinetics. One hundred twenty-two head and neck cancer patients were randomly assigned to receive induction chemotherapy with cisplatin (100 mg/m2, day 1) and 5FU (96-h continuous infusion), either at standard dose (St-arm; 4 g/m2) or at a dose adjusted according to the 5FU area under the curve (AUC0-48h; PK-arm). In total, 106 patients were evaluable for toxicity and response. In the PK-arm (n = 49), 5FU doses and area under the curve were significantly reduced during cycle 2 and cycle 3 (P < 0.001) as compared with the St-arm (n = 57). Grade 3-4 neutropenia and thrombopenia were significantly more frequent in the St-arm as compared with the PK-arm (17.5% versus 7.6%, respectively; P = 0.013). No grade 3-4 mucositis occurred in the PK-arm, whereas 5.1% was observed in the St-arm (P < 0.01). The objective response rate was comparable in the two treatment arms: 77.2% in the St-arm versus 81.7% in the PK-arm. The present study is the first to demonstrate, in a randomized design, the clinical interest of an individual 5FU dose adaptation based on pharmacokinetic survey, in terms of therapeutic index improvement.     

Myofibrosarcoma of the head and neck in children

We have identified a distinctive malignant soft tissue neoplasm that occurred in the head and neck region of six children. Histologically, these neoplasms presented an array of features ranging from low-grade spindle cell to high-grade fibrohistiocytic histologies and often had myoid characteristics. Ultrastructural and immunohistochemical studies indicated that they contained neoplastic myofibroblasts that were variably positive for vimentin (4 positive/4 tested), alpha-smooth muscle actin (4/5), muscle-specific actin (5/5), desmin (2/5), and v-src protein substrate p80/85 (4/5). Three patients died of rapidly progressive unresectable local disease, one died of metastatic and local disease, and two are alive 13 months and 8 years after wide resection. We conclude that these neoplasms form a distinctive subset of pediatric soft tissue sarcomas that display an aggressive clinical behavior, typically with local recurrence, and exhibit features of myofibroblastic differentiation.     

Mucosal melanomas of the head and neck

PURPOSE: To determine the effect of epidural analgesia on biochemical markers of stress, plasma oxytocin concentrations and frequency of uterine contractions during the first stage of labour. METHODS: Nine nulliparous women, in spontaneous labour, with a singleton fetus and cervical dilatation < or = 5 cm were enrolled. Epidural bupivacaine 0.25% (range 10-14 ml) was administered and bilateral sensory blockade to ice (T8-L4) achieved. Blood samples were collected before the epidermal block and every 10 min for one hour after the block was achieved for the measurement of plasma beta-endorphin, cortical, glucose, lactate and oxytocin concentrations. No exogenous oxytocin was given. Intensity of pain was assessed at the time of the blood sampling using a 10 cm visual analogue scale (VAS). The frequency of uterine contractions was recorded for 60 min before and after the epidural block. RESULTS: There was a decrease in plasma beta-endorphin and cortisol concentrations after epidural block (P < 0.01). There were no changes in plasma glucose and lactate concentrations. The mean VAS for pain decreased 10 min after epidural block was achieved and remained < 2 throughout the study period (P < 0.001). Mean plasma oxytocin concentrations did not change. The frequency of uterine contractions before and after the epidural block was similar. CONCLUSIONS: The metabolic stress response to the pain of labour was attenuated by epidural analgesia. In contrast, plasma oxytocin concentration and frequency of uterine contractions were unaffected by the attenuation of metabolic stress response.     

Traumatic neuromas of the head and neck

An interesting case of a traumatic neuroma of the greater auricular nerve provides the impetus for a discussion of head and neck neuromas. Traumatic neuromas of the head and neck are relatively rare. Division of the greater auricular nerve during parotidectomy occasionally results in a traumatic neuroma. We report a case of a 73-year-old woman who presented with a traumatic neuroma nine years after undergoing superficial parotidectomy with dissection of the facial nerve for a mixed tumor. The patient had a 1.5 cm x 1.0 cm mass located below the old surgical site over the anteromedial border of the sternocleidomastoid muscle. The patient's past history was significant for Frey's syndrome, which is the result of abnormal neurologic growth. On first impression, the tumor was thought to be a recurrence of neoplastic disease; however, because of the evaluation, traumatic neuroma was suspected. An attempt at fine-needle aspiration of the mass was too painful to be carried out. At surgery, a whitish tumor was excised which, on final pathologic examination, revealed traumatic neuroma. The surgical literature is reviewed and the subject of head and neck neuromas, including their evaluation and management, is thoroughly discussed. Knowledge of this possible diagnosis may spare the patient and the surgeon needless worry, as well as unnecessary procedures, once tumor recurrence has been ruled out.     

Pediatric rhabdomyosarcoma of the head and neck

PURPOSE: Survival for pediatric rhabdomyosarcoma has improved with the use of multidrug chemotherapy and external beam radiotherapy. This study was performed to determine survival in a cohort of patients treated on one of three multidrug treatment protocols for head and neck rhabdomyosarcoma and to identify factors that place patients at risk for treatment failure. METHODS: Pertinent prognostic variables including age, sex, subsite of origin, resectability, and TNM stage were analyzed by the Kaplan-Meier methods with comparisons between variables performed using the Prentice-Wilcoxon test statistic. RESULTS: Overall 5-year survival was 74% (95% confidence interval 64% to 84%). Local failure accounted for the cause of death in 10 patients, and 8 died of disseminated disease. On univariate analysis, each variable contributing to the TNM staging system was significant in determining survival; invasiveness (P = 0.01), size (P = 0.02), nodal metastases (P <0.01), and distant disease (P <0.01). CONCLUSION: Survival has improved for head and neck rhabdomyosarcoma treated with multimodality therapy. Patients with advanced-stage disease are at greatest risk for treatment failure and require the most aggressive therapy.     

MR angiography of the head and neck

A review of the basic physics and techniques for acquiring and evaluating magnetic resonance angiograms is provided, including time-of-flight and phase contrast techniques. Magnetic resonance (MR) angiography is becoming a routine method of evaluating carotid bifurcation atherosclerotic disease in both a screening and diagnostic capacity. The expanding clinical utility of MR angiography in the detection of intracranial aneurysms, characterization of arteriovenous malformations, and evaluation of intracranial atherosclerotic disease are also reviewed. Furthermore, MR angiography allows for the noninvasive diagnosis of arterial dissection. Magnetic resonance venography also allows the confirmation of the previously elusive and likely underdiagnosed entity of cerebral venous thrombosis.     

Nonnasopharyngeal lymphoepithelioma of the head and neck

BACKGROUND: Lymphoepithelioma (squamous cell carcinoma with associated lymphoid stroma) commonly occurs in the nasopharynx, rarely at other sites. As a result, the clinical course and optimal treatment of nonnasopharyngeal lymphoepithelioma of the head and neck have not been well described. This retrospective study was undertaken to analyze the clinical course of the disease in patients treated at a single institution and to formulate recommendations for treatment based on that experience as well as results reported in the literature. METHODS: Between 1950 and 1994, 34 patients with nonnasopharyngeal lymphoepithelioma of the head and neck were treated at the University of Texas M. D. Anderson Cancer Center. The patients' medical records were reviewed and their pathologic specimens evaluated. The primary tumor sites were: oropharynx (24 patients), salivary gland (4), laryngohypopharynx (4), and the maxillary sinus/nasal cavity (2). Assessed in accordance with the 1992 American Joint Committee Against Cancer TNM staging system, T classifications were TX-2, T1-7, T2-8, T3-10, and T4-7, and N classifications were N0-8, N1-5, N2-15, and N3-6. Treatment consisted of radiotherapy for 24 patients, excisional biopsy of the primary tumor followed by radiotherapy for 7 patients, and surgery for 3 patients. Of the patients treated with radiotherapy, neck dissections were performed on only two, both of whom had persistent lymph node masses after completing radiotherapy. The median dose delivered to the primary tumor was 65 gray (Gy) (range, 46-78 Gy). The median fraction size was 2.1 Gy (range, 1.6-3.2 Gy). RESULTS: The 5-year actuarial disease specific survival and overall survival rates were 59% and 39%, respectively. The 5-year actuarial local control rate for all patients was 94%. For the irradiated patients, the 5-year regional control rates were 77% overall and 83% within the radiation field. The 5-year actuarial rate of distant metastasis for all patients was 30%. For patients who presented with and without regional adenopathy, the 5-year rates of distant metastasis were 36% and 12%, respectively (P = 0.27). CONCLUSIONS: Nonnasopharygeal lymphoepithelioma is a radiosensitive disease. High rates of locoregional tumor control were achieved with radiotherapy at all head and neck sites. The main cause of treatment failure was distant metastasis, which occurred more frequently in patients with lymph node involvement. Radiotherapy is appropriate initial locoregional therapy for patients with this disease. Surgery should be reserved for patients who have persistent disease after completing radiotherapy. Systemic therapy is a reasonable approach for patients who present with regional adenopathy because they have a relatively high rate of distant metastasis.