Impact of tumor control and presence of visible necrosis in head and neck cancer patients treated with radiotherapy or radiochemotherapy

Purpose: Tumor volume after the lymph node involvement is one of the most important single prognostic factor in patients of head and neck cancers treated with radiotherapy. We have recently demonstrated that the hypoxic subvolume is more important than the total tumor volume. We therefore propose the hypothesis that the presence of visible necrosis might be an important factor for cure by radiotherapy in squamous cell cancers of the head and neck. Methods: A total of 51 patients with locally advanced inoperable (T3-4 or N2-3) squamous cell cancers of the head and neck (mean age 57 years, range 41–75 years) were prospectively investigated with regard to a possible impact of tumor volume. All patients received CT examination of the head and neck according to a standardized protocol (spiral CT, contrast enhancement after automatic injection), and the total tumor volume was calculated as the sum of volumes of all visible macroscopic tumor sites. Poorly perfused and necrotic areas (no contrast enhancement) within macroscopic tumor sites were also calculated. Patients were then treated with accelerated-hyperfractionated radiotherapy in about 6 weeks. Seventeen patients were treated with only radiation. Patients without contraindications to cisplatin chemotherapy received cisplatin chemotherapy or a combination of cisplatin and paclitaxel (N=34). The allocation of patients to certain treatment regimens was based on individual decisions in each case and not randomized. Results: In patients treated with radiation alone, 12/17 (71%) got recurrence whereas in patients treated with radiation plus cisplatin, only 14/34 (41%) recurred (P=0.05). The 2-year overall survival was for radiation alone versus radiation plus cisplatin 0% vs. 62% (P<0.0008). Tumors with smaller amount of necrosis (necrosis volume<4 cm³) had a good prognosis irrespective of type of treatment (radiation alone or radiation plus cisplatin). However, patients with tumors with a larger amount of necrosis (necrosis volume≥4 cm³) had a significantly better outcome if they were treated with radiation plus cisplatin as compared to patients treated with radiation alone. In a multi-variate analysis using a Cox-regression model the type of treatment (radiotherapy plus versus without cisplatin) was the only independent prognostic factor for event-free survival (P<0.03) in the whole group. Conclusions: In this non-randomized retrospective investigation with limited sample size, radiation plus cisplatin was superior to radiation alone. This resulted mainly from a higher efficacy of the radiochemotherapy regimen in patients with large and especially necrotic tumors. The prognostic and predictive impact of visible necrosis should be further evaluated.     

Effectiveness of the Cough Reflex in Patients with Aspiration Following Radiation for Head and Neck Cancer

The effectiveness of the cough reflex in patients who aspirated following radiation for head and neck cancer was evaluated in 89 patients (49 chemoradiation, 33 postoperative radiation, and 7 radiation alone). All patients had modified barium swallow because of dysphagia. The cough reflex was graded as present and effective, ineffective, intermittently effective, or absent. All patients were cancer-free at the time of the swallowing study. The cough reflex was present and effective in 46 patients (52%), ineffective in 17 patients (19%), and absent in 26 patients (29%) on initial investigation. Among the 43 patients who had ineffective or absent cough reflex, their treatment was chemoradiation (26), postoperative radiation (13), and radiation alone (4). In 30 patients who had sequential modified barium swallow, the cough reflex was constantly effective, ineffective, or intermittently effective in 12 (40%), 13 (43%), and 5 (17%) patients, respectively. The cough reflex was frequently ineffective or absent in patients who aspirated following radiation for head and neck cancer. Cough may also be intermittently ineffective to protect the airways following radiation.     

Patterns of recurrence and second primary tumors in oral squamous cell carcinoma treated with surgery alone

The aim of the present study is to review the recurrence patterns and incidence of second primary tumors (SPTs) in patients with oral squamous cell carcinoma (OSCC) who underwent surgery alone without postoperative adjuvant therapy. Data on patients recorded in the head and neck cancer registry of Cathay General Hospital were reviewed. A total of 72 patients with T1-3N0 OSCC who underwent surgery alone were included. Among the 72 patients, 44 had T1 tumors, 22 had T2 tumors, and 6 had T3 tumors. The 5-year overall survival (OS) rate was 77.3%, the recurrence-free survival rate was 74.1%, and the SPT-free survival rate was 73%. Eighteen (25%) patients had disease recurrence (regional recurrence in nine patients, local recurrence in seven patients, and locoregional recurrence in two patients). Most patients with local recurrence alone (6/7 patients, 85.7%) could be salvaged with treatment. However, locoregional control was obtained in only five (45.5%) of 11 patients with neck recurrence after surgical salvage therapy. At the time of analysis, 20 patients developed SPTs, and 15 (75%) of the SPTs were in the oral cavity. The annual incidence of SPT was 5%. Neck recurrence and SPT were associated with 48.4% and 24.4% lower 5-year OS rates, respectively. Multivariate analysis revealed that neck recurrence was a significant risk factor for low OS (p = 0.008). Neck recurrence was the most important prognostic factor for OS. The incidence of SPT development was high. Regular and long-term monitoring for recurrence and development of SPTs is necessary to improve the survival rate.     

Evolution of clinical trials in head and neck cancer

The treatment paradigm for locally advanced head and neck cancers has evolved over the past two decades as the role of chemotherapy has been substantiated by clinical trials. Presently, concurrent chemoradiation is considered a standard treatment option for patients with resectable head and neck tumors desiring an organ preservation approach, as well as for patients with locally advanced nasopharyngeal cancers and patients in the postoperative setting who are at high risk for recurrence. The addition of a taxane to induction chemotherapy appears to improve efficacy over cisplatin and 5-FU. Targeted biologic therapies such as the monoclonal antibody Cetuximab has demonstrated efficacy with radiation that appear comparable to chemoradiation combinations and has a favorable toxicity profile. This review will discuss key clinical trials supporting the current standard of care. Emerging new technologies such as intensity modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT) will also be reviewed. Functional assessments and quality of life issues will be addressed.     

Meningitis due to beta-hemolytic non-A, non-D streptococci among adults at a cancer hospital: report of four cases and review.

Four cases of meningitis due to beta-hemolytic non-A, non-D streptococci among adult patients with neoplastic disease are reported. All four patients had head or neck tumors for greater than or equal to 4 years, and all had undergone surgery for these tumors. Three of four patients had received local radiation therapy. None of the patients were neutropenic. One patient died. A review of the literature revealed that most patients with non-A, non-D streptococcal meningitis had disruption of the normal barrier protecting the CNS due to trauma, surgery, or the presence of a tumor, or had extensive exposure to animals or an underlying medical disease. Infection with non-A, non-D streptococci should be considered in any patient with meningitis who has a tumor of the head or neck and who has undergone surgery and/or radiation therapy.     

Concurrent chemoradiation for patients with squamous cell carcinoma of the cervical esophagus

Little is known concerning the role of concurrent chemoradiation (CCRT) in the management of carcinoma of the cervical esophagus. We retrospectively evaluated our treatment approach for patients with cervical esophageal cancer with special emphasis on CCRT with or without surgery. Medical records of 21 consecutive patients with cervical esophageal carcinoma treated mainly with CCRT (1997-2004) were reviewed, and factors that influenced patient survival were analyzed retrospectively. Nineteen received CCRT with cisplatin/5-fluorouracil and five underwent curative surgery. Two patients who were deemed unfit for CCRT received radiation therapy alone. All had three-dimensional treatment planning (median total dose, 40 Gy with surgery, 64 Gy without surgery). Of the 19 patients who received CCRT, 11 patients including five who underwent curative surgery achieved initial local control. Neither of the two patients who received radiation therapy alone achieved local control. Among 19 patients who underwent CCRT, 9/11 with T1-3 grade tumors achieved initial local control, but only 2/8 patients with T4 tumors (P = 0.011, chi(2) test) achieved initial local control. No patient without initial local control survived > 20 months compared with 2-year and 5-year survival rates of 60% and 40% in those who achieved initial local control (P = 0.038). No patient with T4 tumors survived > 18 months, whereas 2- and 5-year survival rates were 62% and 41%, respectively, in those with T1-3 tumors (P = 0.006). The significant effect of T-classification on survival was maintained when analyzed among 19 patients who received CCRT. CCRT shows promise for cervical esophageal carcinoma. T-classification and initial local control had significant impact on survival.     

Combination chemotherapy used prior to radiation therapy for locally advanced squamous cell carcinoma of the head and neck

Thirty-three patients with locally advanced squamous cell carcinoma of the head and neck were scheduled to receive two courses of chemotherapy prior to radical radiotherapy. Chemotherapy consisted of moderate-dose methotrexate with leucovorin rescue, bleomycin by infusion, and cisplatin. Loss of body weight and the duration of membrane formation at a specified region of the oral cavity during radiation therapy were used as indices of radiation toxicity: there was no excessive loss of body weight or mucosal reaction in patients who received combined treatment compared to patients in a nonrandomized control group who received radiotherapy alone. Twenty patients (60%) had a greater than or equal to 50% decrease of measurable disease prior to starting irradiation, but only eight patients (24%) are alive and disease-free at a median followup of 16 months. Aggressive chemotherapy does not prevent delivery of subsequent full-dose radiotherapy for squamous cell carcinoma of the head and neck, but this study does not suggest that chemotherapy has a great beneficial effect on long-term survival.     

cis-Dichlorodiammineplatinum(II)-based chemotherapy as initial treatment of advanced head and neck cancer.

During the past 2--3 years, a total of 73 patients with advanced head and neck cancer (mostly stage IV) were treated with cis-dichlorodiammineplatinum(II) (cis-platinum) as initial therapy, either alone or in combination with other agents. After chemotherapy, the patients received surgery and/or radiation therapy in standard fashion. Major degrees of tumor regression were seen in 40%--71% of the patients. cis-Platinum and bleomycin given by infusion gave the highest response rate (71%). The addition of high-dose methotrexate to cis-platinum plus bleomycin produced an unacceptable level of toxicity. Similarly, a four-drug regimen in which low-dose methotrexate and vinblastine were added to cis-platinum and bleomycin resulted in increased toxicity without additional therapeutic effect. Initial chemotherapy does not compromise subsequent surgery or increase either the immediate complications of surgery or the acute toxicity of radiation therapy. It seems unlikely that initial chemotherapy has altered the grim prognosis of an advanced, inoperable presentation. The effect of initial chemotherapy on advanced, operable disease will have to be assessed by suitable controlled trials.     

Diagnosis of hidden central hypothyroidism in survivors of childhood cancer

To determine how often central hypothyroidism remains undetected by routine out-patient tests of thyroid hormone, we studied 208 pediatric cancer survivors referred for evaluation because of signs of subtle hypothyroidism or hypopituitarism. Of the 208 (68 females and 140 males), 110 had brain tumors, 14 had other head/neck tumors, 11 had solid tumors remote from head and neck, and 73 had leukemia. Patients were evaluated 1-16 yr (mean, 6.1+/-4.1 yr) after tumor diagnosis. The nocturnal TSH surge and response to TRH were measured. Of 160 patients with free T4 in lowest third of normal, 34% had central hypothyroidism (blunted TSH surge or low/delayed TSH peak or delayed TSH decline after TRH); 9% had central hypothyroidism with mild TSH elevation (mixed hypothyroidism). Another 16% had mild primary hypothyroidism (TSH, 5-15 mU/L). Of 48 with free T4 in the upper two thirds of normal, 14% had central hypothyroidism; 17% had mild primary hypothyroidism. Incidence of central, mixed, and mild primary hypothyroidism 10 yr after tumor diagnosis was significantly related to total cranial radiation dose (P < 0.0001). Of 62 patients with central hypothyroidism, 34% had not developed GH deficiency. TSH surge identified 71%, and response to TRH identified 60% of those with central hypothyroidism. More than half of the slowly growing patients who have received cranial or craniospinal radiation for childhood cancer develop subtle hypothyroidism. In our study group, 92% of patients with central hypothyroidism and 27% with mixed hypothyroidism would have remained undiagnosed using baseline thyroid function tests alone. Both TSH surge and response to TRH must be evaluated to identify all of these patients.     

Therapeutic effect of oral recombinant human granulocyte macrophage-colony stimulating factor in radiotherapy-induced esophagitis

BACKGROUND/AIMS: Radiation-induced esophagitis is one of the most important early side effects of irradiation of chest, and head and neck malignancies. This condition often leads to interruption of radiotherapy for several days. An effective treatment for reducing the incidence and severity of this complication has not yet been found. We aimed to investigate the therapeutic effect of rhGM-CSF on radiation-induced esophagitis in the patients with chest or head and neck malignancies. METHODOLOGY: Ninety-seven patients with chest or head and neck malignancies who had not previously received radiation therapy, were treated with radiotherapy, concurrent or sequential chemoradiotherapy. Forty-eight patients who had grade 1, 2 or 3 esophagitis symptoms according to Radiation Therapy Oncology Group radiation morbidity score, underwent upper gastrointestinal endoscopy. In the patients with grade 3 esophagitis (according to Kuwahata's scoring system) rhGM-CSF was administered for 5-10 consecutive days as an oral solution. RESULTS: Endoscopic examinations showed grade 3 esophagitis in 26 of these patients according to Kuwahata's score. Twenty-five patients with grade 3 esophagitis were given rhGM-CSF therapy. Radiotherapy was continued in 23 patients. After the rhGM-CSF therapy, esophagitis had regressed from grade 3 to grade 0 in 10 (43%), from grade 3 to grade 1 in 8 (35%), and from grade 3 to grade 2 in 3 patients (12%). Two patients (9%) did not respond to rhGM-CSF therapy. Twenty-one patients (91%) completed planned radiotherapy without interruption. CONCLUSIONS: In patients with radiation-induced esophagitis, ulcerated esophageal mucosa healed with local granulocyte macrophage-colony stimulating factor administration in median 8 days without radiotherapy interruption.     

Radiotherapy of 180 cases of operable esophageal carcinoma

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Quadruple cancer,including triple cancers in the head and neck region

Multiple primary tumors are not rare: they are encountered in 3-5% of malignant tumors. They are particularly frequent in the head and neck [20]. They are most often met with secondary malignant tumors; triple tumors occur in only 0.5%, quadruple tumors in 0.3% of malignant tumors. The possibility of developing a second metachronous cancer 5 years after undergoing treatment of the initial head and neck cancer is approximately 22%. Multiple metachronous tumors often appear 3-4 years after the observation of the primary tumor, or even after 5-10 years in the case of laryngeal tumors. The frequency of multiple primary tumors in the head and neck region supports the "field cancerization" theory, according to which the inducing agents (primarily smoking and alcohol consumption) can initiate the tumorous degeneration at a number of sites in the oropharyngeal region. The authors report on a case in whom surgery for bladder tumor was followed 101 months later by tumor development in the region of the head and neck: 3 such tumors were treated within a period of 21 months. The histologic result on the bladder tumor was transitiocellular carcinoma, while the latter ones were squamous cell carcinomas. Three of the tumors were treated effectively (no local recurrence or metastasis developed), but the fourth led to the death of the patient. The literature on multiple tumors of the head and neck is reviewed, and possible etiologic factors are discussed. It is pointed out that, besides primary and secondary prevention, close observation of these patients is required, repeated panendoscopy of the upper aerodigestive tract and genetic examinations are recommended.     

误诊为风湿性疾病的皮下脂膜炎样T细胞淋巴瘤八例临床分析

目的 探讨皮下脂膜炎样T细胞淋巴瘤(SPTCL)临床特征,以提高临床诊断与治疗水平.方法 回顾分析北京协和医院收治的8例经病理确诊的SPTCL临床资料,包括临床表现、误诊情况、实验室检查、病理检查、治疗及转归.结果 8例患者中男4例,女4例,发病至确诊28.6(4～84)个月,初诊均考虑为风湿病(结节红斑、结节性脂膜炎、系统性血管炎等);临床主要表现为皮下结节、肿块、斑块,结节均为多发,可累及四肢、躯干、头面部;部分伴发热(7例),肝(3例)、脾(3例)、淋巴结肿大(4例),3例伴噬血细胞现象.8例患者先后共行活检22例次,平均2.75(1～5)例次,涉及多个部位,最终确诊为SPTCL.病理显示,病变均位于皮下脂肪组织内,表现为大量淋巴细胞浸润,细胞异型性明显;免疫组化:CD_3阳性多见,1例基因重排T细胞受体阳性,表达γδSTCR.确诊SPTCL前,抗风湿药物(糖皮质激素、免疫抑制剂)治疗效果不佳,确诊SPTCL后,6例经化疗病情稳定.2例因肺部浸润及感染死亡.结论 SPTCL临床表现多样,容易误诊为脂膜炎等风湿病.临床表现为反复皮下结节,抗风湿治疗效果不佳,病理活检并免疫组化及T细胞受体重排PCR检测可明确诊断.     

Combined radiotherapy and bleomycin for advanced head and neck cancers: results of a phase I pilot study

Forty-two patients with inoperable stage III or IV head and neck epithelial tumors were entered in a phase I pilot study to evaluate the toxicity and efficacy of combined radiotherapy and bleomycin for advanced head and neck cancers. Twenty-three patients (52%) achieved complete remissions and 18 patients (42%) had greater than 50% regression. Most patients tolerated bleomycin at a dose of 5 units twice a week, with a full course of radiotherapy delivered at 1809 rads/day, 5 days/week. Although the complete remission rate appears to be higher than with radiotherapy alone and 13 of the 23 complete remissions (57%) lasted greater than 1 year, methods of prolonging the duration of remission need to be developed.     

Effects of systemically administered bleomycin or adriamycin with local hyperthermia on primary tumor and lung metastases.

Exposure of cells in tissue culture to bleomycin or Adriamycin during 43 degrees C hyperthermia increased cytotoxicity dramatically compared to exposure at 37 degrees C. This study was designed to test whether this interaction was useful in tumor-bearing animals. C3H mice bearing the KHT tumor were treated with bleomycin (7 or 15 mg/kg) or with Adriamycin (2.5 or 5 mg/kg) with or without local heating of the tumor to 43 degrees C for 30 minutes by 13.56 MHz radiofrequency fields. The effects were assessed by growth delay (mean tumor diameter doubling time) and cure rate. In separate experiments, BALB/c mice bearing EMT6 tumors were treated identically, but tumors were excised 2 hours after treatment and tumor cell survival was assayed by colony formation. Antitumor effects of systemic bleomycin were potentiated by local hyperthermia. The two modalities had to be administered close together in time to observe the potentiation, suggesting a true interaction. There was a "threshold" for bleomycin potentiation in vivo between 42 degrees C and 43 degrees C, just as observed in tissue culture experiments. The antitumor activity of Adriamycin was not potentiated in vivo in these tumor systems except in cell survival experiments at doses higher than those compatible with survival of the host. The toxicity of drug combined with heat was greater than that of either modality alone. Hyperthermia did not adversely affect the incidence or severity of spontaneous lung metastases from KHT tumors. In fact, groups treated with heat and bleomycin had less severe lung metastases than groups treated with bleomycin alone. We conclude that local heating of tumors may be a useful adjunct to systemic bleomycin therapy. In vivo potentiation of Adriamycin by heat, however, could not be demonstrated in these tumor systems.     

Bacterial Brain Abscess: An Outline for Diagnosis and Management

Despite advances in the diagnosis and management of brain abscess, significant associated morbidity and mortality remain high. We retrospectively reviewed adults who presented with pyogenic brain abscess from January 1, 2009, through June 30, 2020. Overall, 247 patients were identified. The median age was 59 years, and 33.6% had a history of head and neck surgery or traumatic brain injury. Diagnostic brain magnetic resonance imaging (MRI) was performed in the bulk (93.1%) of patients. A total of 205 patients (83%) were managed with medical and surgical treatment. The most common definitive antibiotic regimen was monotherapy (48.2%). The median duration of antimicrobial therapy was 42 days. Compared with those who received combined therapy, patients with medical therapy alone had a higher mortality rate (21.4% vs 6%; P =. 003) with more neurologic sequelae (31% vs 27.1%; P = .5). Most patients with brain abscesses are older with multiple underlying comorbidities, and one-third had antecedent head and neck surgery. A prompt combined surgical and medical approach with prolonged antimicrobial therapy may cure the infection with avoidance of permanent residual neurologic deficits.     

Interferon-associated retinopathy in a uniform regimen of natural interferon-alpha therapy for chronic hepatitis C.

BACKGROUND/AIMS: The development of retinal lesions induced by a uniform regimen of interferon-alpha therapy for chronic hepatitis C was prospectively investigated. METHODS: Eighty-one patients received 6 mega units of natural interferon-alpha intramuscularly daily for 2 weeks and then 3 times a week for 22 weeks. The total dose of interferon-alpha administered was uniformly 478 mega units per patient. Two expert ophthalmologists prospectively examined the patients for retinal lesions before, during and after the therapy. RESULTS: Retinopathy was not found in comparison groups or any of the patients before treatment. In total 34.6% (28/81) of the patients showed cotton-wool spots or minor retinal hemorrhage, or both lesions, during therapy, but these lesions were reversed during or after interferon therapy. The occurrence rates of cotton-wool spots alone, retinal hemorrhage alone and both lesions were 13.6% (11/81), 6.2% (5/81), and 14.8% (12/81), respectively. The appearance of retinopathy did not correlate with patients' background including viral loads and response to the therapy, but was more frequently found in older patients and patients with hypertension and/or diabetes mellitus; disappearance of retinopathy was more prolonged than in patients without these complications. Almost all the lesions appeared 2-4 months after the start of the therapy, and the severity of the lesions did not differ between patients with and without hypertension and/or diabetes mellitus. CONCLUSION: Although it is not clear if interferon-associated retinopathy occurs in a dose-dependent manner, the present study shows a standard pattern of the occurrence of retinopathy in patients with chronic hepatitis C receiving a uniform dosage of natural interferon-alpha.     

Continuous infusion high-dose leucovorin with 5-fluorouracil and cisplatin for untreated stage IV carcinoma of the head and neck

STUDY OBJECTIVE: To study the activity of continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin (PFL) as induction chemotherapy in patients with previously untreated, advanced squamous cell carcinoma of the head and neck. DESIGN: Nonrandomized, prospective trial. SETTING: A comprehensive cancer center. PATIENTS: Thirty-five patients (4 patients [11%], stage III; 31 patients [89%], stage IV [MO]), all evaluable for response and toxicity. INTERVENTIONS: Two to three cycles of PFL before definitive, local-regional therapy (surgery and radiation therapy or radiation therapy alone). Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2 body surface area daily, days 1 through 5); 5-fluorouracil (800 mg/m2 body surface area daily, days 2 through 6); and leucovorin (500 mg/m2 body surface area daily, days 1 through 6) administered once every 28 days. Pathologic response was evaluated by surgical resection or biopsy. Serum-reduced folates were measured before and 18 hours after the initiation of chemotherapy. RESULTS: A clinical response to PFL was achieved in 28 of 35 (80%) patients: 23 (66%) patients had a complete response (90% CI, 50% to 79%) and 5 (14%) patients, a partial response. A complete response was confirmed pathologically in 14 of 19 (74%) patients. The most common toxicity was mucositis (grade 2 to 3; 94% of patients). Dose reduction for toxicity was necessary in 11 (31%) patients. There were no treatment-related deaths. Serum levels of leucovorin and (6S)5-methyltetrahydrofolate were measured in 7 patients. After 18 hours, the mean leucovorin level (+/- SD) was 34.3 +/- 1.5 mumol/L, of which only 8.0 +/- 0.5% was the active 6S isomer. The mean serum (6S)5-methyltetrahydrofolate was 9.2 +/- 0.6 mumol/L. CONCLUSIONS: Continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin is a new and highly active chemotherapy regimen that can achieve clinical and pathologically confirmed complete responses in a substantial proportion of patients with advanced, local-regional squamous cell carcinoma of the head and neck. Further studies are needed to confirm the activity of PFL and to determine its potential impact on local tumor control and disease-free and overall survival.     

Hyperthermia,radiation carcinogenesis and the protective potential of vitamin A and N-acetylcysteine

The in vivo carcinogenic risk of hyperthermia, alone or in combination with irradiation, and the anti-carcinogenic potential of vitamin A andN-acetylcysteine (AcCys) were investigated. Starting 1 month before treatment, 160 rats were divided into four diet groups: no additives, vitamin A-enriched diet, AcCys and the combination vitamin A+AcCys. In 10 animals per diet group, the hind leg was treated with either X-irradiation alone (16 Gy), hyperthermia alone (60 min at 43°C), hyperthermia 5 h prior to irradiation or hyperthermia 5 h after irradiation. Animals were observed for 2 years after treatment with regard to the development of tumours either inside or outside the treated volume. After 16 Gy alone 12±5% of the animals developed a tumour. Tumour incidence increased to 37±9% (borderline significanceP=0.07 versus treatment with X-rays alone) when hyperthermia was applied prior to X-rays, and to 24±8% (NS) with hyperthermia after irradiation. The relative risk ratio (RRR) for tumour induction was increased to 2.4 by hyperthermia if combined with X-irradiation. Pathological characterization of induced tumours showed that these were of the fibrosarcoma, osteosarcoma and carcinoma type. Vitamin A alone or in combination with AcCys slightly protected against the induction of tumours by X-rays without or with hyperthermia (RRR of 0.4). However, morphological changes such as lipid accumulation in hepatocytes and damage to the parenchyma were noticed in livers from all animals that were given a vitamin-A-enriched diet (P<0.0001). Data from the present and past reports show that hyperthermia alone is not carcinogenic, but that it may increase radiation carcinogenesis. Treatment temperature and time of exposure to heat in addition to the radiation dose applied are important factors in the carcinogenic process. The enhancement of radiation carcinogenesis seems to occur independently of the sequence and time interval between irradiation and hyperthermia. However, not all data are consistent with this interpretation.Presented in part at the 4th symposium Experimentelle Strahlentherapie und klinische Strahlenbiologie 23–25 February 1995, Hamburg, Germany, and at the 10th International Congress of Radiation Research, 27 August–1 September 1995, Würzburg, Germany. The investigation was supported by the Interuniversitair Instituut voor Radiopathologie en Stralenbescherming, grant IRS 7.1.4.     

Focal uptake of (18)F-fluorodeoxyglucose by thyroid in patients with nonthyroidal head and neck cancers

OBJECTIVE: To evaluate the prevalence and significance of focal thyroid lesions identified by (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients with nonthyroidal head and neck cancers (HNC). PATIENTS AND MEASUREMENTS: Patients with histologically identified HNC who underwent FDG-PET and computed tomography (CT) were reviewed retrospectively. We evaluated the prevalence of patients with focal thyroid FDG uptake and the risk of malignancy and proper management in these patients. RESULTS: Of 689 HNC patients, 19 (2.8%) had focal thyroid FDG uptake. Of the 12 patients with a histological diagnosis by surgery or needle biopsy, 5 (41.7%) had carcinomas, 4 papillary and 1 follicular, whereas the others had benign thyroid lesions. The maximum standardized uptake value on PET was not sufficient to discriminate between malignant and benign thyroid lesions (8.4 +/- 13.2 vs. 4.2 +/- 4.0; P > 0.4). The identification of incidental thyroid diseases helped guide patient counselling and combined surgery with HNC and thyroidectomy. CONCLUSION: Focal thyroid lesions incidentally found on FDG-PET in patents with nonthyroidal HNC have a high probability of malignancy. These lesions deserve further diagnostic examination before HNC treatment to ensure adequate therapy for incidental thyroid cancers.