Effect of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography-guided management of suspected recurrent papillary thyroid carcinoma: long-term follow-up with tumour marker responses.

AIMS: To investigate the use of recombinant human thyroid-stimulating hormone-stimulated co-registered (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for detecting suspected recurrent papillary thyroid carcinoma among patients with rising tumour markers but negative whole-body iodine-131 scans. Tumour marker responses to (18)F-FDG PET/CT-guided therapy were also measured for these patients. MATERIALS AND METHODS: A prospectively gathered (18)F-FDG PET/CT database and patient charts were reviewed. Patients having previously undergone total thyroidectomy and ablative iodine-131 therapy for papillary carcinoma before (18)F-FDG PET/CT were analysed. RESULTS: Nineteen patients formed the study population: 12 women and seven men, median age 49 years, with elevated thyroglobulin (n = 15), elevated anti-thyroglobulin antibody (n = 4); the median follow-up was 46 months, range 27-56 months. Sixteen patients (84%) had a positive PET/CT scan (15 with disease confined to the head and neck and one with distant disease), whereas three patients (16%) had a negative scan. Eleven of the 15 patients with disease confined to the head and neck underwent potentially curative salvage therapy: surgery (n = 7), external beam radiotherapy (n = 2) or both (n = 2). All patients undergoing surgery had histological confirmation of malignancy. At a median follow-up of 50 months for these 11 patients, eight had detectable tumour markers at levels below pre-scan values, two had levels above, and one patient had an undetectable level. All three patients with negative PET/CT scans were placed on surveillance. At a median follow-up of 45 months for these three patients, two had tumour marker levels below pre-scan values and one had an undetectable level. CONCLUSIONS: Recombinant human thyroid-stimulating hormone-stimulated (18)F-FDG PET/CT detected recurrent disease in most patients. Although subsequent treatment of (18)F-FDG PET/CT-detected disease reduced tumour marker levels in most patients, markers remained detectable, suggesting that not all residual or metastatic disease had been identified, which compromised salvage therapy. This is the largest and most mature study to date reporting tumour marker responses to PET- or PET/CT-guided therapy in this setting.

Predictors of positive radial margin status in a population-based cohort of patients with rectal cancer.

BACKGROUND: Surgical margin status is an important predictor of risk of relapse among patients with rectal cancer. METHODS: Patients referred to the British Columbia Cancer Agency for consideration of adjuvant therapy for rectal adenocarcinoma were included. Predictors of margin positivity were determined from uni- and multivariate analysis. RESULTS: Among 340 patients, 83% had negative resection margins. In 268 patients with resectable tumours, a significantly higher rate of margin positivity was observed in low rectal tumours (32.2%) as compared with mid-rectal (3.9%) and high rectal (14.3%) tumours. Among 59 patients with locally advanced rectal cancer treated with preoperative radiation (with or without chemotherapy), 32% with low tumours had margin positivity. Of patients with T4 tumours, 50% (11/22) had a positive resection margin. CONCLUSIONS: In a population cohort, distal-third rectal location, locally advanced presentation, and T4 cancer represent subgroups for whom further improvement in therapy is required.

Anaplastic thyroid cancer in British Columbia 1985-1999: a population-based study.

AIMS: To review the outcome of patients diagnosed with anaplastic thyroid carcinoma in British Columbia between January 1985 and December 1999. MATERIALS AND METHODS: Seventy-five patients were identified. Survival curves were calculated using Kaplan-Meier estimates, and the charts of the 62 patients referred to a British Columbia Cancer Agency (BCCA) facility were reviewed. RESULTS: All cases: 51 out of 75 patients (68%) were women; median age of all patients was 74 years. The overall- and cancer-specific 5-year survival rates for the whole group were 5%. non-referred cases: nine out of 13 patients were women; median age at diagnosis 84 years. Eleven of the 13 patients died within 1 month of diagnosis. Referred cases: 42 out of 62 patients were women; median age 72 years; median survival 5.1 months; 1-year survival 19%. Forty-eight patients presented with tumours that extended through the thyroid capsule, 10 presented with distant metastases. Four patients had a total thyroidectomy, nine a partial thyroidectomy, and 49 a biopsy only. Fifty-seven patients received radiotherapy, nine of these had concurrent chemotherapy: Thirty-three patients received less than 40 Gy and 24 patients received 40 Gy or more. Median survival was longer (9 vs 3 months) in patients receiving 40 Gy or more; this group included four patients who had prolonged survival. CONCLUSION: Long-term, disease-free survival was achieved in a few patients who were able to receive high-dose radiotherapy, preferably after adequate surgery.

Local control of T3N0 glottic carcinoma by 60 Gy given over five weeks in 2.4 Gy daily fractions. One more point on the biological effective dose (BED) curve.

Seventy patients with T3N0 glottic cancer who received a total dose of 60 Gy in twenty-five 2.4 Gy daily fractions over 5 weeks had an initial post radiation primary recurrence free rate of 65% at 5 years. This provides one more point for the dose response for T3 glottic cancer Radiother Oncol (1999) 15.

Cancer of the tonsil: the results of ipsilateral radiation treatment.

BACKGROUND AND PURPOSE: The use of ipsilateral irradiation techniques to treat patients with carcinoma of the tonsil reduces the acute radiation reaction in the contralateral pharynx and late damage to the contralateral salivary tissue. However, this may also spare microscopic disease in apparently uninvolved contralateral lymph nodes. The purpose of this study was to analyse the survival and recurrence rates and sites of recurrance in a group of patients with carcinoma of the tonsil treated with ipsilateral techniques. MATERIALS AND METHODS: Between 1975 and 1993, 271 patients with invasive squamous cell cancer of the tonsil were referred to the Vancouver Cancer Centre (VCC). One hundred and seventy-eight received ipsilateral radiation treatment. Three received surgery only, six post-operative radiation, 12 supportive treatment only and 72 bilateral radiation treatment. In the absence of bilateral neck nodes and extensive lymphodenopathy, field sizes were generally kept small to include the primary tumour and the first echelon of nodes. The most common dose was 60 Gy in 25 daily fractions in 5 weeks (2.4 Gy per day). RESULTS AND DISCUSSION: The disease specific survival for all patients treated by radical radiation treatment was 61% at 5 years. For the 178 patients who received ipsilateral radiation treatment the overall primary tumour control rate by ipsilateral radiation treatment alone was 75% and for T1 and T2 tumours 84%. Eight (7.5%) of 101 of these patients with N0 nodes at presentation and without prior failure at the primary site, developed nodal recurrence (four within the initially radiated high dose volume). Two developed contralateral nodes, and two developed field edge nodal recurrence, one cured by surgery. In 54 patients with N1 disease, five developed nodal recurrence, two within field, two contralateral, one of whom was cured by surgery, and one at field edge. In 23 patients with N2a, N2b or N3 disease node control was achieved from radiation treatment in 11 and two more were cured by surgery. All nodal failures were within the radiated volume. Overall, 10 of the 25 patients with nodal failure were cured by subsequent surgery. CONCLUSIONS: Ipsilateral treatment of patients with carcinoma of the tonsil gives survival results that are at least as good as those reported with bilateral treatment with fewer side effects and a very low risk of failure in the contralateral neck.

Transanal local excision of selected low rectal cancers.

BACKGROUND: To determine if transanal local excision (TALE) of selected early low rectal cancer is an effective alternative to more radical resection and to determine the need for adjuvant radiotherapy in these patients. METHODS: A retrospective analysis of all 47 cases referred for consideration of radiotherapy after TALE for low rectal cancer. RESULTS: Indications for TALE were elective, 32; concurrent medical problems, 11; and refusal of radical resection, 4. Median follow-up was 52 months. Local recurrence occurred in 7 of 27 T1 cases, 5 of 17 T2, and 2 of 3 T3. Three of 23 irradiated patients developed local recurrence, compared with 11 of 24 unirradiated (P = 0.023). Of 28 cases with favorable histological features, 1 of 13 irradiated patients developed local recurrence, compared with 4 of 16 unirradiated (P = 0.22). Seven patients had salvage resection, and 3 of these are alive with no evidence of disease at 21, 39, and 71 months postsalvage. Recurrence-free survival at 5 years was 81 % in the irradiated patients and 52% in the unirradiated (P = 0.025). CONCLUSIONS: Transanal local excision of selected low rectal cancers, combined with adjuvant radiotherapy, results in a low recurrence rate and is, therefore, an effective alternative to more radical resection.

A randomised trial of accelerated versus conventional radiotherapy in head and neck cancer.

BACKGROUND AND PURPOSE: To study the effect of accelerated radiation treatment in locally advanced head and neck cancer, a prospective randomised trial was conducted comparing two fractionation schemes which differed only in the overall treatment time; fraction size and total dose were the same in both arms. MATERIALS AND METHODS: Eighty-two patients with stage 3 or 4 squamous cell cancer of the oral cavity, oropharynx, hypopharynx or larynx considered suitable for radical radiotherapy as primary treatment were stratified by site and stage and randomised to receive 66 Gy in 33 2 Gy daily fractions in 45-48 days (o.d.) or 66 Gy in 33 2 Gy twice daily fractions in 22-25 days (b.i.d.). RESULTS: An initial improved clinical response in tumour control in the b.i.d. arm was not sustained and the 3 year recurrence free survival and overall survival rates were similar and not significantly different. The actuarial recurrence free survival was 49.1% in the b.i.d. arm and 44.3% in the o.d. arm. The disease free 3 year survival was 59.4% and 56.8%, respectively. The acute and late normal tissue effects were scored using the RTOG scale. As expected the acute effects were much greater in the b.i.d. arm. The combined grade 3 and 4 late effects were similar but the proportion of grade 4 reactions was significantly higher in the b.i.d. arm. The increase in grade 4 toxicity caused the trial to be discontinued after 82 of the planned 226 patients had been randomised. CONCLUSIONS: The severity of the normal tissue effects and a failure to demonstrate sustained local control does not support this fractionation scheme in patients with such extensive head and neck cancer.

Seven fractions of twice daily high dose-rate brachytherapy for node-negative carcinoma of the mobile tongue results in loss of therapeutic ratio.

From June 1989 to December 1993, a Phase I/II protocol using high dose-rate (HDR) interstitial brachytherapy for early stage node-negative squamous cell carcinoma of the mobile tongue was undertaken to assess the toxicity and efficacy of this modality. A total of 27 patients were treated: T1-10 patients, T2-15 patients, and T3-two patients. Seven fractions x 6.5 Gy of HDR brachytherapy were given on a twice daily schedule, with a minimum interval time of 6 h, over a period of 3.5 days. The actuarial tumor control probability after HDR brachytherapy was 53% at 5 years. Local control rates for the T1 and T2 tumors were lower than comparable historical controls treated at our institution using low dose-rate (LDR) radium or cesium needle implants and iridium wire implants. This is despite the fact that the HDR schedule was calculated by the linear quadratic formula to have equal tumor killing effects as 60 Gy in 6 days of LDR radiation. In addition, there was a trend towards higher incidence of severe complications for the HDR patients compared to historical controls treated with LDR. We would caution against the use of this schedule of HDR brachytherapy until further studies are done.

A preliminary investigation of an association between dental restorations and carcinoma of the tongue.

The potential association of dental restorations and tongue carcinoma was studied. We reviewed the available pretreatment dental records of 133 patients with carcinoma of the tongue seen at the British Columbia Cancer Agency between 1958 and 1992. 75 patients had teeth adjacent to the ipsilateral side of the cancer (involved side) and the contralateral (control) side of the tongue, resulting in 150 tongue/teeth pairings. Overall there was no significant association between the presence of dental fillings and tongue carcinoma, as the prevalence of bilateral dental restorations was high. Dental restorations were found in 6 patients on the involved side only. Only 1 patient developed a cancer adjacent to normal teeth with contralateral restorations. We feel that this observation merits more study. Meanwhile, careful assessment of dentition and aggressive treatment of dysplastic lesions are warranted.

Impact of cervical lymph node metastases from squamous cell cancer of the lip.

The records of 123 patients with squamous cell cancer of the lip presenting to the Vancouver Clinic of the British Columbia Cancer Agency from 1984 and 1988 were reviewed, and 4 were excluded from the study for various reasons. Initial treatment was surgery in 40, radiotherapy in 61, and combined in 18 patients. The primary tumor was staged as TIS in 11, T1 in 57, T2 in 24, T3 in 15, T4 in 1, and undetermined in 11. Follow-up continued for a minimum of 2 years in all but five patients. Lymph node metastases developed in 19 patients, representing 18% of the 108 patients with invasive cancer. The size of the primary tumor correlated with the likelihood of metastases. The neck disease was controlled in only 8 of the 19 patients with metastases, whereas control of the primary tumor was achieved in all but 3 patients. It is concluded that the development of node metastases in patients with lip cancer is more frequent than commonly appreciated and is associated with a high mortality rate. Close follow-up is essential to allow early detection of neck involvement. Aggressive surgery is indicated when such involvement becomes evident.

Phase I study of concurrent carboplatin and radiotherapy in previously untreated patients with stage III and IV head and neck cancer.

This study evaluated the toxicity resulting from combined therapy using carboplatin and radiotherapy in 22 patients with locally advanced (stage III and IV) head and neck cancer. Carboplatin was given after radiotherapy during the first 5 consecutive days of a 16-fraction course of radiotherapy delivered in a total of 22 days. To find the acceptable toxic dose of carboplatin, the patients were treated in groups of 3 patients each. The first group received 50 mg/m2 carboplatin and the dose was increased by 10 mg/m2 in each subsequent group. Unacceptable toxicity (severe mucositis, nausea and vomiting, and/or myelosuppression) was encountered at a carboplatin dose of 80 mg/m2. A further 10 patients were then treated at a dose of 70 mg/m2. At this dose toxicity was acceptable. Although the group of 22 patients is too small for response and survival data to be meaningful, 10 complete responses were seen and median survival is in excess of 67 weeks.

Sequential uterine horn versus simultaneous total uterine flush to recover bovine embryos nonsurgically.

Beef cows were superovulated with follicle stimulating hormone (FSH) to compare two nonsurgical methods of embryo recovery from the uterus. In the first method each uterine horn was independently flushed with physiological saline solution (PSS) through a Foley catheter passed through the cervix and into the uterine horn. In the second method both uterine horns were simultaneously flushed with PSS by passing the catheter into the uterine body. In both methods, the numbers of ovulations were determined after embryo collection by counting the corpora lutea (CL) on both ovaries of each cow through a flank incision. Independent flushing (n = 19) averaged 6.4 embryos and 16.1 CL per cow for a recovery rate of 40%. Simultaneous flushings (n = 22) averaged 5.4 embryos and 17.7 CL per cow for a recovery rate of 31%. This difference between the recovery rates of the two flushing methods was not significant (P>0.05).

Impact of new radiotherapy modalities on the surgical management of cancer of the esophagus and cardia.

At the Cancer Control Agency of British Columbia, 483 patients with cancer of the esophagus and cardia were seen from 1970-1980. Four hundred and one out of 483 (83%) had tumors larger than 5 cm (T2) and in 288/483 (60%) the disease had extended beyond the esophageal wall (T3). The overall 5-year survival rate was only 9% for all patients treated by external irradiation. The 5-year survival for a selected group having esophagectomy was 20%. Most patients died of persistent cancer at the primary site (83%); the cause of death was aspiration pneumonia (82%) due to obstruction caused by the persistent cancer. Our most recent experience using intracavitary irradiation either prior to or after external irradiation in 211 patients has been safe and simple and preliminary analysis of treatment results suggests that it has improved the therapeutic ratio. The analysis of quality of life at 6 months following therapy as it relates to performance status, swallowing ability, weight, and pain indicated significant improvement in all of these parameters. Of 171 patients, 33% were still alive at 1 year, 26% at 2 years, and 19% at 3 years following treatment. Of 43 patients suitable for preoperative irradiation, only 26 patients were actually resected and 19 of them are still alive with no evidence of disease, 8 to 30 months. The rationale and technical aspects of the combined treatment are described in detail. Treatment results, complications and an outline for future programs based on this experience are also described.

The growth and histological characteristics of a series of human bladder cancer xenografts.

Xenografts from human transitional cell carcinoma of the bladder (TCC) have been successfully established in CBA mice which had previously been immune-deprived by thymectomy and whole body irradiation with cytosine arabinoside pre-treatment. Xenografts were established from 3/17 patients with histological grade 2 tumours, 3/19 patients with histological grade 3 tumours, and one from a patient with a mixed transitional cell and squamous cell carcinoma. No xenografts were established from patients with histological grade 1 tumours. All the xenografts maintained the histological characteristics of their parent tumours in early passage, but some developed more prominent squamous features in later generations. Many of the xenografts were cystic.

Case report: Salmonella pneumonia associated with chemotherapy for non-Hodgkin's lymphoma.

Patients with malignant disease are frequently at risk of developing a wide range of infective disorders as a result of their immunosuppressed state. The case reported here describes a rare manifestation of a common infection, Salmonella, in a patient undergoing treatment for lymphoma.

The suitability of immunosuppressed mice kept in a standard animal unit as recipients of human tumour xenografts.

CBA/Lac mice were immunosuppressed by thymectomy and whole body irradiation with 250 kVp X-rays following pretreatment with cytosine arabinoside. The optimum radiation dose for immunosuppression with prolonged survival was 7.35 Gy. The animals were kept in a standard animal unit with an overall survival rate of 83%. They were found to be suitable for large scale, long-term, xenotransplantation experiments at 20% of the cost of nude mice.

Tumorigenicity of human lymphoblastoid cell lines, acquired during in vitro culture and associated with chromosome gains.

Tumorigenicity of human lymphoma and lymphoblastoid B-cell lines was assessed by their ability to form growing and transplantable masses on subcutaneous inoculation into neonatally thymectomized, Ara-C-protected, total-body-irradiated mice. By these criteria, 12 lines of known malignant origin were tumorigenic, 11 lymphoblastoid lines, tested after less than one year of in vitro growth, were non-tumorigenic and 8/18 long-established lymphoblastoid lines produced transplantable tumours. All of the long-established lines had acquired karyotypic changes on prolonged culture, the predominant characteristic being a gain of whole chromosomes or of major chromosome segments. None showed the classical 8:14 translocation associated with Burkitt's lymphoma. Comparisons with nontumorigenic precursors (recovered from liquid nitrogen storage) and with other non-tumorigenic but chromosomally abnormal, lymphoblastoid lines suggest that imbalance of the dosage of genes carried on chromosomes 7,8 and 9 may be important in determining the tumorigenic phenotype.

Subsequent malignancies in patients irradiated for testicular tumours.

897 patients received radiotherapy in Scotland for tumours of the testis between 1950-1969. 299 patients who died within two years of treatment, and a further 51 patients with inadequate follow-up data, were excluded from a survey of the incidence of second tumours. 547 patients with a mean follow-up of 15.4 years were included in the study. Fifty-one second and six third malignancies were found. The observed incidence is significantly higher than expected (ratio 1.87; p less than 0.001), both in the irradiated sites (ratio 1.94; p less than 0.05) and in unirradiated sites (ratio 1.99; p less than 0.01). These patients have a higher incidence of second testicular tumours (ratio 23.1; p less than 0.001). Analysis of the incidence of new malignancies in successive quinquennia after irradiation shows a significantly higher incidence in two periods. Within five years the greater incidence (p less than 0.05) is due mainly to the occurrence of second testicular tumours. In the period 15-19 years after irradiation the higher incidence (p less than 0.01) is accounted for by tumours arising in the urinary and gastro-intestinal tracts. The increased risk of developing a second cancer is low and there was no observed increase in radiation-related leukaemia.

Radiotherapy of testicular tumours: an analysis of patients treated in Scotland between 1950 and 1969.

The results of treatment of 838 patients who were irradiated for germ cell tumours of the testis between 1950 and 1969 are presented. The overall 10-year survival rate was 61.8%. For seminomas alone it was 75.3% and for teratomas 37.7%. No increase in survival was found which could be attributed to the introduction of megavoltage beams.