Ellen Benhamou

Long-term results and prognostic factors in patients with differentiated thyroid carcinoma

A multivariate analysis of the prognostic factors was carried out on a series of 546 differentiated thyroid cancers followed for 8 to 40 years. For survival, the highest risk factor was associated with age; tumors diagnosed in patients younger than 45 years had higher relapse‐free survival (RFS) and total survival (TS) rates and a slower growth rate. In children, although the RFS and TS at 15 years were high, they decreased later. The second independent prognostic factor was histology. There was no difference between papillary and follicular well‐differentiated (FWD) tumors, but follicular moderately differentiated (FMD) had lower TS and RFS. Among FMD cancers, relapses occurred earlier and the interval between relapse and death was shorter. The third factor was sex. Tumors tended to disseminate more in male than in female patients. The survival rate after relapse was the same, however, suggesting that the growth rates are not different. The presence of palpable lymph nodes also had a significant independent impact on both TS and RFS. Patients treated after 1960 have a better outcome than patients treated earlier, although they did not differ in age distribution, histologic characteristics, sex ratio, or incidence of palpable lymph nodes. The distribution of time intervals between treatment and relapse was not compatible with an exponential failure time model but fit with a log‐logistic model. Relapses can occur as late as 30 years or more after initial treatment. Elevated levels of circulating thyroglobulin have been observed in about 12% of the patients who had been in complete remission for longer than 20 years.

Strategies of Radioiodine Ablation in Patients with Low-Risk Thyroid Cancer

BACKGROUND It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care. METHODS In our randomized, phase 3 trial, we compared two thyrotropin-stimulation methods (thyroid hormone withdrawal and use of recombinant human thyrotropin) and two radioiodine ((131)I) doses (i.e., administered activities) (1.1 GBq and 3.7 GBq) in a 2-by-2 design. Inclusion criteria were an age of 18 years or older; total thyroidectomy for differentiated thyroid carcinoma; tumor-node-metastasis (TNM) stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (with tumor diameter ≤1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage, or pT2N0; absence of distant metastasis; and no iodine contamination. Thyroid ablation was assessed 8 months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin-stimulated thyroglobulin. Comparisons were based on an equivalence framework. RESULTS There were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the (131)I doses and between the thyrotropin-stimulation methods. CONCLUSIONS The use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; ClinicalTrials.gov number, NCT00435851; INCa number, RECF0447.).

Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study.

Basal cell carcinomas (BCCs) are very frequent cutaneous cancers, often located on the face. Cure rates with surgery and radiotherapy are high, but these treatments have never been compared prospectively. A randomized trial was initiated in 1982 to compare surgery and radiotherapy in the treatment of primary BCC of the face measuring less than 4 cm. The primary end point was the failure rate (persistent or recurrent disease) after 4 years of follow-up. The secondary end point was the cosmetic results assessed by the patient, the dermatologist and three persons not involved in the trial. In the course of the trial, 347 patients were treated. Of the 174 patients in the surgery group, 71% had local anaesthesia and 91% frozen section examination. Of the 173 patients in the radiotherapy group, 55% were treated with interstitial brachytherapy, 33% with contactherapy and 12% with conventional radiotherapy. The 4-year actuarial failure rate (95% CI) was 0.7% (0.1-3.9%) in the surgery group compared with 7.5% (4.2-13.1%) in the radiotherapy group (log-rank P = 0.003). The cosmetic results assessed by four of the five judges were significantly better after surgery than after radiotherapy. Eighty-seven per cent of the surgery-treated patients and 69% of the radiation-treated patients considered the cosmetic result as good (P < 0.01). Thus, in the treatment of BCC of the face of less than 4 cm in diameter, surgery should be preferred to radiotherapy.

RANDOMISED PLACEBO-CONTROLLED TRIAL OF HEPATITIS B SURFACE ANTIGEN VACCINE IN FRENCH HAEMODIALYSIS UNITS: II, HAEMODIALYSIS PATIENTS

A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in 138 haemodialysis patients in a placebo-controlled randomised double-blind trial. In an interim analysis, hepatitis B infections were observed in 21% of the vaccine group and 45% of the placebo group (p less than 0.02). 2 of the infections in the vaccine group and 12 of the infections in the placebo group occurred after the third injection. 60% of the vaccine recipients had an immune response. 4 months after the first injection the mean titre of anti-HBs was 120 mlU/ml.

Prevention of oral mucositis in patients treated with high-dose chemotherapy and bone marrow transplantation: A randomised controlled trial comparing two protocols of dental care

Between February 1986 and November 1989, 166 patients who were candidates for a bone marrow transplantation entered a randomised controlled clinical trial to compare limited oral hygiene care (LIM) and intensive oral hygiene care (INT) in the prevention of mucositis. Randomisation was stratified on the initial oral status (good vs. bad IOS). Intensive oral hygiene care included an initial treatment of dental lesions and tooth and gum brushing during aplasia. Limited oral hygiene care excluded preventive dental treatment and gingival and tooth brushing. Mucositis was classified as absent, mild, moderate or severe, according to the clinical aspects of the different sites in the mouth and to two scales of pain evaluation. Of the 150 evaluable patients (75 in each group), 134 developed moderate/severe mucositis (64 in the INT group and 70 in the LIM group) (log-rank test P < 0.02). The superiority of intensive oral care was observed both in patients with and without total body irradiation (TBI) and in patients with a good or bad IOS; the observed risk of mucositis was reduced by 70% in each of these four subgroups. Duration of moderate/severe mucositis was, although not significantly, lower in the INT group (17 days, S.D. = 12) than in the LIM group (19 days, S.D. = 13). The median time of mucositis occurrence was 11 days in the INT group and 9 days in the LIM group. Contrary to a widespread belief, the percentage of documented septicaemia was not higher in patients who underwent intensive oral care. We conclude that, although statistically significant, the superiority of intensive oral hygiene care is not clinically impressive.(ABSTRACT TRUNCATED AT 250 WORDS)

RANDOMISED PLACEBO-CONTROLLED TRIAL OF HEPATITIS B SURFACE ANTIGEN VACCINE IN FRENCH HAEMODIALYSIS UNITS: I, MEDICAL STAFF

A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in staff members from forty-eight French haemodialysis units where the risk of hepatitis B was high. Of 318 subjects who completed the protocol, 164 received three monthly injections of vaccine and 154 received corresponding injections of placebo. Hepatitis B infection was observed in 3.6% of the vaccine group and 12.3% of the placebo group (p less than 0.005). The 6 infections in the vaccine group all arose within 63 days from the first injections, whereas the 19 in the placebo group arose throughout the 12 months of follow-up. The rate of side-effects after injection did not differ in the two groups. 94% of the vaccine recipients had an immune response ( greater than 10 mIU/ml in at least 5 successive specimens). 4 months after the first injection the mean + or - 2 SE peak level of anti-HBs was 2433 + or - 1077 mIU/ml.

Cosmetic results following lumpectomy axillary dissection and radiotherapy for small breast cancers

Between 1970 and April 1982, 592 women with T(1), small T2, N0, N1, M0 breast cancer were managed by lumpectomy, axillary dissection and radiotherapy at the Institut Gustave-Roussy (IGR). The overall cosmetic result and the degree of asymmetry, fibrosis and telangiectasia of the treated breast were assessed by the radiation oncologist at each follow-up visit. The changes in these cosmetic parameters with time are shown. At 5 years the overall cosmetic result was excellent in 59%, good in 38% and fair or poor in 8%. A multivariate analysis was performed of the factors associated with a cosmetic defect. The most significant factors were tumour size, the presence of defect after surgery and the daily applied dose per fraction to the breast. Surgical and radiotherapy technique (especially alternate day fractionation) can significantly affect the cosmetic result obtained.

Management of the axilla in conservatively treated breast cancer: 592 Patients treated at institut Gustave-Roussy

Between June 1970 and April 1982, 592 patients with unilateral T1 and small T2 breast cancers were managed conservatively at the Institut Gustave-Roussy. The treatment policy for the axilla was to perform a lower axillary dissection and to proceed to axillary clearance ( +/- radiotherapy) in patients with axillary invasion by tumor (N+). Some N+ patients had only lower axillary dissection and radiotherapy. Five hundred fifty-eight patients underwent axillary surgery which was a lower axillary dissection in 374 patients (67%) and axillary clearance in 184 patients (33%). There was axillary invasion in 198 cases (36%). Only five patients relapsed in the axilla and the probability of axillary relapse at 5 years was 1.2%. There were no axillary relapses in N+ patients who had had an axillary clearance whether irradiated or not. The incidence of upper limb complications was significantly greater in patients undergoing axillary surgery and radiotherapy compared with axillary surgery alone (p less than 0.0001). It is concluded that a lower axillary dissection accurately identifies N-patients and an axillary clearance in N+ patients ensures good local control and avoids the morbidity associated with axillary irradiation.

Local relapse and contralateral tumor rates in patients with breast cancer treated with conservative surgery and radiotherapy (institut gustave roussy 1970–1982)

Background. Breast conservation is now established treatment for patients with small breast cancers. The authors reviewed a large series of patients with long term follow‐up who underwent conservative treatment. Clinical and pathologic factors were analyzed to identify patients at an increased risk of relapse in the breast (local relapse) or development of a contralateral tumor.

Single dose versus hyperfractionated total body irradiation before allogeneic bone marrow transplantation: a non-randomized comparative study of 54 patients at the Institut Gustave-Roussy

At the Institut Gustave-Roussy (IGR), from January 1982 to December 1986, 54 patients received total body irradiation (TBI) as a part of the conditioning regimen before allogeneic bone marrow transplantation. The patients were non-randomly assigned to either single dose TBI (STBI) (31 patients receiving 10 Gy at a 4.5 cGy/min dose rate, 8 Gy to the lungs) or to a hyperfractionated scheme (HTBI) (23 patients receiving 13.2 Gy in 11 fractions, 3 fractions per day, 9 Gy to the lungs). Relapse rate and overall survival were not significantly different in the two STBI and HTBI groups, in spite of a larger number of 2nd and 3rd remission patients in the HTBI subset. The incidence of interstitial pneumonitis (IP) was significantly reduced in the HTBI group (13%, versus 45% after STBI, p = 0.02). Lethality by IP was also lower after HTBI (4%, versus 26% after STBI, p = 0.08). There was no case of veno-occlusive disease of the liver in the HTBI group, whereas three cases were observed after STBI. Based on these results, the IGR activated, in January 1987, a randomized trial comparing the single dose 10 Gy TBI (8 Gy to the lung) to a new hyperfractionated schedule (11 fractions of 1.35 Gy, 3 fractions per day, 9 Gy to the lungs).