To assess the skin toxicity of this scheme and the time to its appearance.
Eighty-one prospectively recorded patients (pts), treated in Radiotherapy Department for Breast Cancer (BC) with radiotherapy (RT) to the whole breast at the dose of 42.9Gy per 13 fractions (F) per 5 weeks have been studied. Skin reactions were monitored weekly using the National Cancer Institute-Common Toxicity Criteria scoring system, version 3. All risk factors as tobacco smoking, diabetes, obesity were also recorded.
All 81 pts, aged from 40 to 83 years (median: 70 years) received whole breast RT 42.9Gy per 13 F without lymph node irradiation after breast conserving surgery. There were no pts with concurrent chemo- and/or hormonal therapy. Seventeen patients (21%) have been treated using decubitus dorsal (DD) technique and 64 (79%) using the previously described isocentric decubitus lateral (IDL) technique. During the RT, only 34 pts (42%) experienced grade I skin reactions and 47 pts (58%) were without. At the last day of the breast irradiation, there were 66 (81%) grade I (N=59) and II (N=7) skin reactions and 15 pts (19%) without. The early skin tolerance of this scheme was considered to be excellent. But in the 2 weeks after the RT, 20 pts (25%) asked for new clinics with their radiation oncologist as a matter of urgency due to worsening of their skin condition. All of them have been seen by their physician and/or the nurse. Of them, nine presented grade I and 11 presented grade II skin reactions, with necessity of special skin care. The analysis of these results was realized and delayed clinics were organized for all pts treated with this scheme 10-14 days after the end of the radiation treatment.
The breast RT 42.9Gy/13 F have been previously described as an efficacious and well tolerated scheme. This prospective homogeneous group of patients showed that delayed early skin reactions could appear in some cases. Therefore complementary clinics are needed to detect and treat these reactions.
Retrospective analysis of result of radical cystectomy at Cochin Hospital.
We report the results of a 106 patients series treated by radical cystectomy for bladder carcinoma after a 5-year period follow-up.
The extent of the tumour invasion according to pathological analysis was: pT1 or less: 26%, pT2 and pT3a: 33%, pT3b and over: 41%. Morbidity rate was 19% with a 7.5% reintervention rate. Long term complication rate was 31%, concerning essentially ureteral stenosis. A local recurrence or distant metastasis occurred in 35% of patients. Local recurrence rate was 10.7%. Cancer specific survival rates were 88%, 81% and 42% for pT1, pT2-pT3a, and pT3b patients respectively.
The present results confirm that radical cystectomy is the most effective curative treatment for invasive bladder carcinoma.
To evaluate survival and prognostic factors of 108 patients with clinically or mammographically detected ductal carcinoma in situ (DCIS), treated from 1980 to 1996 by complete local excision followed by external irradiation.
The median age was 51 (range 37-80). All the patients underwent surgery consisting of a wide resection of the mammary gland harbouring the tumour. The surgical specimens were sent to the pathologists to get information on histology and margin clearance; all the slides were reviewed by one of us to assess the tumoral diameter. External beam therapy was delivered within 8 weeks after surgery. The prescribed irradiation dose was 50 Gy in 25 fractions to be given in 5 weeks. The median duration of follow-up was 93 months (range 40-173).
There were nine patients with local recurrence (8.3%); three patients had local recurrence of DCIS and six patients developed invasive breast cancer. The treatment of local recurrence consisted of mastectomy with or without axillary dissection (eight cases) and quadrantectomy (one case). The 5-year and 10-year ipsilateral recurrence-free rate was respectively 92 and 89%. The 10-year cause specific survival was 100%. In univariate analysis, size>or=10 mm, age<45 years old and margin status were significant P=0,02, P=0,03, P=0,005; margin status was significant in multivariate analysis (P<0,02).
These results are in keeping with those of the literature. They could be improved by the mass screening campaign, which is going on since January 1990 among women aged 50-74 years.
Retrospective analysis of analgesic, decompressive and remineralization effects of radiation therapy for spinal metastases in breast cancer.
From January 1990 to December 1992, 108 patients with breast cancer were treated by irradiation at the Bergonié Institute for a first spinal metastasis. Three patients had undergone previous surgery (laminectomy and Doves' frame). The indication of radiation therapy was analgesic (102 patients) or decompressive (six patients). The usual irradiation scheme was 30 Gy/10 fractions/2 weeks.
The analgesic effect was considered as 'complete' or 'almost complete' (83%), 'moderate' (13%) or absent (4%). The mean time to the maximum analgesic response was 35 days. The duration of both the analgesic response and remineralization effects could not be retrospectively assessed due to lack of data. Decompressive effects were complete in five cases and absent in one case. A second spinal radiation therapy was necessary 78 times (eight times in junction field within 6 months following the first treatment). Spinal cord compression occurred either out of (three cases) or within (one case) the irradiated field.
Radiation therapy for spinal metastases in breast cancer remains a palliative analgesic treatment. Indication for decompression is rare. However, assessment of compressive 'risk' leads to discussion of radiological staging (contribution of magnetic resonance imaging) and possible previous treatment (vertebroplasty or osteosynthesis).
To investigate the impact of the boost dose to the primary tumour bed in the framework of breast conserving therapy on local control, cosmetic results, fibrosis and overall survival for patients with early stage breast cancer.
Five thousand five hundred and sixty-nine patients after lumpectomy followed by whole breast irradiation of 50 Gy were randomised. After a microscopically complete lumpectomy (5318 patients), the boost doses were either 0 or 16 Gy, while after a microscopically incomplete (251 patients) lumpectomy randomisation was between 10 and 26 Gy. The results at a median follow-up of 10 years are presented.
At 10 years, the cumulative incidence of local recurrence was 10.2% versus 6.2% for the 0 Gy and the 16 Gy boost groups (p < 0.0001) and 17.5% versus 10.8% for the 10 and 26 Gy boost groups, respectively (p > 0.1). There was no statistically significant interaction per age group but recurrences tended to occur earlier in younger patients. As younger patients had a higher cumulative risk of local relapse by year 10, the magnitude of the absolute 10-year risk reduction achieved with the boost decreased with increasing age. Development of fibrosis was significantly dependent on the boost dose with a 10-year rate for severe fibrosis of 1.6% after 0 Gy, 3.3% after 10 Gy, 4.4% after 16 Gy and 14.4% after 26 Gy, respectively.
An increase of the dose with 16 Gy improved local control for patients after a complete lumpectomy only. The development of fibrosis was clearly dose dependent. With 10 years median follow-up, no impact of survival was observed.
Keloid scars are unsightly, especially when located on the face or bare zones. The purpose of this study was to evaluate the therapeutic results of intraoperative brachytherapy in the management of keloids.
This retrospective study was based on the study of 82 patients with keloids treated in Salah Azaiz Institute (Tunisia) between 1982 and 1994 (65 women and 17 men). The mean age of patients was 23.4 years (+/- 8.4). A total of 114 lesions have been treated with surgical resection and intraoperative brachytherapy using an iridium source placed under the surgical scar. The length of iridium was chosen with the result that the radioactive thread exceeded 5 mm on each side of the surgical scar. The iridium source was loaded less than six hours after resection. Average iridium activity was 1.5 +/- 0.3 mCi/cm. Average iridium length was 56.8 +/- 34 mm. The referred isodose chosen for the target volume included the surgical scar and a margin of 5 mm around the iridium source, which was placed under the surgical scar. The average administered dose was 20.4 Gy (+/- 3.2 Gy).
The 2-year local control rate was 87% for the whole group of lesions treated (n = 114). Local control rate of keloids processed by resection and intraoperative brachytherapy as the first treatment (59 cases) was 96% at two years. This rate was better than the local control of lesions that had been previously treated with anterior surgical resection (84% in 55 cases). For the latter group, lesions treated with a dose of more than 20 Gy had better local control, but the difference was not statistically significant (87 vs. 65% at two years, P = 0.41).
Intraoperative brachytherapy is effective for improving local control of keloids and preventing a recurrence. A rigorous technique and an adequate dose according to previous surgical treatment allows very good results.
To evaluate our updated data concerning survival and locoregional control in a study of locally advanced non inflammatory breast cancer after primary chemotherapy followed by external preoperative irradiation.
Between 1982 and 1998, 120 patients (75 stage IIIA, 41 stage IIIB, and 4 stage IIIC according to AJCC staging system 2002) were consecutively treated by four courses of induction chemotherapy with anthracycline-containing combinations followed by preoperative irradiation (45 Gy to the breast and nodal areas) and a fifth course of chemotherapy. Three different locoregional approaches were proposed, depending on tumour characteristics and tumour response. After completion of local therapy, all patients received a sixth course of chemotherapy and a maintenance adjuvant chemotherapy regimen without anthracycline. The median follow-up from the beginning of treatment was 140 months.
Mastectomy and axillary dissection were performed in 49 patients (with residual tumour larger than 3 cm in diameter or located behind the nipple or with bifocal tumour), and conservative treatment in 71 patients (39 achieved clinical complete response or partial response >90% and received additional radiation boost to initial tumour bed; 32 had residual mass <or=3 cm in diameter and were treated by wide excision and axillary dissection followed by a boost to the excision site). Ten-year actuarial local failure rate was 13% after irradiation alone, 23% after wide excision and irradiation, and 4% after mastectomy (p =0.1). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumour size (<6 vs. >or=6 cm in diameter, p =0.002). Ten-year overall metastatic disease-free survival rate was 61%. After multivariate analysis, metastatic disease-free survival rates were significantly influenced by clinical stage (stage IIIA-B vs. IIIC, p =0.0003), N-stage (N0 vs. N1-2a, and 3c, p =0.017), initial tumour size (<6 vs. >or=6 cm in diameter, p =0.008), and tumour response after induction chemotherapy and preoperative irradiation (clinically complete response + partial response vs. non-response, p =0.0015). In the non conservative breast treatment group, of the 32 patients with no change in clinical tumour size after induction chemotherapy, the 10-year metastatic disease-free survival rate was 59% with only one local relapse. Arm lymphedema was noted in 17% (14 of 81) following axillary dissection and in 2.5% (1 of 39) without axillary dissection. Cosmetic results were satisfactory in 70% of patients treated by irradiation alone and in 51.5% of patients after wide excision and irradiation.
Despite the poor prognosis of patients with locally advanced non inflammatory breast cancer resistant to primary anthracycline-based regimen, aggressive locoregional management using preoperative irradiation and mastectomy with axillary dissection offers a possibility of long term survival with low local failure rate for patients without extensive nodal disease. On the other hand, the rate of local failure seems to be high in patients with clinical partial tumour response following induction chemotherapy and breast-conserving treatment combining preoperative irradiation and large wide excision.
To describe the biochemical failure-free survival (BFFS), GU toxicity and erectile dysfunction in intermediate risk prostate cancer treated with iodine 125 monotherapy (I125).
Between October 1994 and October 2007, 1282 patients were treated with I125 at the Hotel Dieu de Quebec. Two hundred patients were intermediate risk prostate cancer. One hundred and fifty-seven had enough follow-up to be evaluated in this study. Biochemical failure-free survival is reported using Phoenix definition. Acute and late GU toxicity was described using the International Prostate Symptoms Score (IPSS) as well as with the rate of bladder catheter. Erectile dysfunction was also reported.
The mean age of the patients was 65.6 years (S.D.=6 years) and the mean pretreatment PSA was 8.7ng/ml. About half of the patients (51%) were T2b/T2c. About 44.6% had a PSA greater than 10 and 4.5% had Gleason score of 7/10. More than half of the patients received a short course of hormones of less than 6 months for cytoreduction (57.4%). The median follow-up was 60 months. Biochemical failure-free survival at 60-month and 96-month were 87.1% and 81% according to Phoenix definition. The mean IPSS rose from 5 immediately after the implant to 15 1 month after and then slowly decreased to 8 at 24 months. Acute urinary retention with bladder catheter occurred in 10.9% of patients. Only 4.3% presented erectile dysfunction at 5 months post-implant.
I125 monotherapy for intermediate risk prostate implant gives biochemical failure-free survivals at 5 years and 8 years comparable to those obtained with high dose external beam radiotherapy. GU toxicity and erectile dysfunction were low and acceptable. Therefore, the use of I125 alone in this group of patients could be presented and discussed with the patient in the waiting of phase III validation.
To analyse a new technique for prostate brachytherapy with permanent Iodine implants characterized by the use of a seed projector after a 3D dosimetric peroperative treatment planning (FIRST technique).
395 patients have been treated in France with this technique in six radiotherapy centres between November 2002 and December 2005 for a localized prostate cancer.
Thirteen patients (3.3%) developped a urinary retention, and respectively 7.8 and 26.5% an acute RTOG grade 3 and 2 toxicity. The 6-weeks IPSS score was equal or lower to 15 in 73% with a 11 median IPSS value. A failure of the loading with the seed-projector, leading to a manual loading of the seeds, occurred in 9 patients (2.3%) in two centres, directly related to the loading procedure with the seed-projector in 5 cases. The median duration of the procedure was reduced by 30 minutes for the patients treated in 2005.
This multicenter study establishes the feasibility of the routine use of a seed projector for permanent iodine 125 prostate implants with an initial tolerance similar to the best results published for other implants techniques.
To study the number of migrating seeds, the anatomical site of migration and possible predictive parameters of migration, after prostate cancer brachytherapy using a loose-seed (I125) implantation technique.
The charts of the 170 patients consecutively treated by the Institut Curie/Hospital Cochin/Hospital Necker Group between September 1, 2001 and August 31, 2002, were analysed. All seeds having migrated to the lungs and seen on the chest X-ray systematically performed at 2 months, have been recorded, as well as the seeds lost by the urines (after sieving) or in the sperm (condom).
Among 12,179 implanted seeds, 44 were found to have migrated (0.36%). Most of the migrating seeds (32/44; 73%), were found in the lungs. Overall, one or several seed migrations were observed in 35 patients (21% of the total number of patients in this series). In the majority of cases (77%), only one seed migrated. A significant relationship (P = 0.04) was found between the number of migrating seeds and the number of implanted ones (or with the prostate volume, but those two parameters were closely linked in our series). More specifically, a significant relationship (P = 0.02) could be demonstrated between the number of seeds implanted at the periphery of the prostate and the number of seeds migrating to the lungs.
The percentage of migrating seeds observed in this series is low, actually one of the lowest found in the literature when using the loose-seed technique. There was no clinical consequences and the loss of-usually-only one seed is very unlikely to alter the quality of the dose distribution. However, the predominance of pulmonary migrations in our series led us to slightly modify our implantation technique. We now try to avoid too "peripheral" seed implantations, due to the risk of migration towards the periprostatic veins, and subsequently to the lungs.
A French decree of February 3rd 2005, allowed the Iodin 125 seeds from several companies to be reimbursed after a permanent implantation brachytherapy for a prostate cancer. Within this frame, the French "Comité économique des produits de santé" (CEPS; Economic committee for health products) made mandatory the annual writing and publication of a follow-up study with three main aims; make sure that the seeds were used for prostate cancer patients with criterias corresponding to the national recommendations, analyze the quality of the dosimetric data, and report all side effects, complications and possible accidents. We therefore report here a clinical and dosimetric analysis of 469 patient cases treated in France in nine centers in 2005 with the Iodin 125 IsoSeed Bebig. This analysis shows that: 1) The national recommendations for selecting patients for exclusive prostate brachytherapy have been taken into account in 97% of the cases; 2) The dosimetric quality criterias totally fulfilled the recommendations in a large majority of cases; the intra-operative D90 was found to be superior to 145 Gy in 98% of the patients, and the intra-operative V100 was superior to 95% in 96% of the cases; 3) The early toxicity (mainly urinary) was found to be at the lower range of what is reported in the literature, with in particular a retention rate of 2.4%.
Evaluation of acute urinary toxicity following prostate Iodine-125 brachytherapy and determination of risk factors.
Between September 2000 and July 2001, 50 men were entered into the study. A clinical follow-up accompanied by an objective measurement of urinary morbidity, including uroflowmetry and post-void residue, enabled the evaluation of acute toxicity before and then at one, three and six months of the implantation. Predictors were also searched for.
38 (76%) patients developed urinary disorders but those remained minor or moderate. The IPSS, as well as uroflowmetry deteriorated significantly at the first and third month post-implant, before improving during the sixth month. Besides, the variations of the post-void residue were less significant. Concerning the factors of risk, an initial IPSS superior to eight and a prior alpha-blocker treatment were the preoperative identified risk factors. Regarding dosimetric parameters, preoperative U30 and postoperative D90, D95, V100, V150 and V200 were identified.
Though remaining minor or moderate, the great frequency of acute urinary toxicity following prostate brachytherapy requires frank and open dialogue with the patient in conjunction with an evaluation of the urinary status before implantation Patients with higher initial IPSS or having required a prior alpha-blocker treatment are more exposed to these disorders and their correlated postoperative dosimetric factors.
Iodine 125 curietherapy is one of the conservative treatments of uveal melanoma. The technique used to achieve these results was simplified through the physical characteristics of the radioelement and the optimized-dosimetry program employed.
78 patients with choroidal melanoma were treated with iodine 125. About 100 Gy were delivered to the superior pole of the tumour. The minimal length of follow-up was 17 months and the average, 67 months.
There was 88% local control, leading to lowered visual acuity in 76% of the cases. Radiation retinopathy, directly related to proximity to the macula, is the principle etiology. Seven patients died of hepatic metastasis, five patients were enucleated. Four patients were further treated with protontherapy to make up for noncontrol locally.
One dose of 100 Gy to the superior pole of the tumor seemed to lead to good local control, with the exception of complications related to proximity to the macula and the optic nerve. In this attempt to optimize irradiation, the time lapse between any benefit in local control derived from irradiation and posttherapeutic complications observed remains insufficient to evaluate any relationship.
Post-implant CT-based dosimetry is the only method of assessing the quality of permanent prostate brachytherapy. As a consequence of our permanent feedback with the preplanned technique, geometric and dosimetric criteria for optimal seed implantation are proposed and pre and post-implantation dosimetric results are presented.
In 2000 and 2001, one hundred and twenty patients with early stage prostate cancer were treated with transperineal I-125 preplanned brachytherapy (RAPID Strand, Amersham Health). The prescription dose was 145 Gy to the planning target volume. For the pre-planning and post-implant dosimetry the Variseed 6.7 version software was used (Varian Medical Systems). The D90, V100 and V150 values, the position of the dose peak [Dose] peak) and the full width at half maximum (FWHM) on differential dose volume histogram from both planned and post-implant dosimetry were compared for all patients.
For preplanned dosimetry, the mean values for D90, V100, V150, [Dose] peak, FWMH were respectively of 199Gy, 100%, 70%, 220Gy, 113Gy. For post-implantation, these values became respectively of 157Gy, 90%, 62%, 220Gy, 194Gy.
In our practice, differences are noted between preplanned and post-implant dosimetry parameters that should be anticipated to assure optimal definitive result. A working methodology both for performing the preplanned dosimetry and for evaluating the post-implantation dosimetric results is proposed.
For patients with good urinary function and presenting with a low risk prostate cancer, prostate brachytherapy using iodine implants represents one of the techniques of reference. This retrospective analysis investigates urinary (U), digestive (D) and sexual (S) toxicities and their prognostic factors of duration.
From August 2000 to November 2007, 176 patients presenting with prostate adenocarcinoma underwent interstitial brachytherapy. Urinary, digestive and sexual toxicities were classified according to Common toxicities criteria for adverse events, version 3.0 (CTCAE V3.0). For each toxicity (U, D, S), the number of complications U (dysuria, nicturia...), D (proctitis, diarrhea...) and S (sexual dysfunction, loss of libido, ...) was listed and analyzed according to criteria related to the patient, implant, dosimetric data and characteristics of the toxicity. Prognostic factors identified in univariate analysis (UVA) (Log Rank) were further analyzed in multivariate analysis (MVA) (Cox model).
With a median follow-up of 26 months (1-87), 147 patients (83.5 %) presented urinary toxicities. Among them, 29.5 % (86 patients) and 2.4 % (seven patients) presented grade 2 and 3 U toxicity respectively. In UVA, urinary grade toxicity greater than or equal to 2 (p=0.037), the presence of initial U symptoms (p=0.027) and more than two urinary toxicities (p=0.00032) were recognized as prognostic factors. The number of U toxicities was the only prognostic factor in MVA (p=0.04). D toxicity accounted for 40.6 % (71 patients). Among them, 3 % (six patients) were grade 2. None were grade 3. Two factors were identified as prognostic factors either in UVA and MVA: the number of D toxicities greater than or equal to 2 (univariate analysis: p=0,00129, multivariate analysis: p=0,002) and age less than or equal to 65 years (univariate analysis: p=0,004, multivariate analysis: p=0,007). Eighty-three patients (47.4 %) presented a sexual toxicity; 26.9 % (49 patients) and 5 % (nine patients) were scored as grade 2 and 3 respectively. A number of seeds greater than 75 (p=0.032) and S grade greater than or equal to 2 (p<0.0001) were recognized as prognostic factors in UVA. S grade was the only prognostic factor in MVA (p=0.0015).
The duration of U, D and S toxicity is strongly correlated with a high number of toxicities and the grade of toxicity. This analysis allows for better information given to the patient regarding the duration of the post-treatment complications.
Brachytherapy with permanent implants is a validated method of treatment of prostate adenocarcinomas of favourable prognosis. Its technology is based on endorectal ultrasonography and on peroperative visualisation of the implant and the dose distribution. A strict selection of the patients is necessary before this localised treatment. An active collaboration between urologists, radiophysicists and radiation oncologists is necessary during all the process of selection, treatment and follow-up of the patients. An assessment of the carcinologic and functional results is necessary. Recommendations are formalized by a joint collaboration between members of the AFU and of the SFRO.
The purpose of this study was to establish a pre-therapeutic score that could predict which patients would be at high risk of enteral tube feeding during (chemo)-radiotherapy for head and neck cancer.
A monocentric study was conducted retrospectively on patients receiving a radiotherapy or concurrent chemoradiotherapy for a head and neck cancer. A logistic model was performed in order to assess clinical or therapeutic risk factors for required artificial nutrition during treatment. Significant parameters, issued from multivariate analysis, were summed and weighted in a score aiming at estimating a malnutrition risk during radiotherapy.
Among the 127 evaluated patients, 59 patients required artificial nutrition during radiotherapy. In multivariate analysis, predictive factors for malnutrition were weight loss superior to 5% in the 3 months before radiotherapy, advanced tumor stage (III-IV vs. I-II), and pain requiring strong analgesics (step II-III vs. I). Concurrent chemotherapy was identified as a significant risk factor also, but it was strongly correlated with the tumor stage. The score, estimated from these previous factors, allowed a prediction of a risk of enteral feeding with a sensitivity of 90% and a specificity of 85%.
A predictive score of enteral nutrition before radiotherapy of head and neck cancer should be a useful clinical tool to target the patients who would need a prophylactic gastrostomy. Our study evidenced some risk factors of malnutrition requiring artificial feeding. However, we need a prospective study to confirm the validity of this score.
Though Hodgkin's disease (HD) is one of the malignancies in which considerable progress has been made, long-term side effects have been observed, second primary cancer being the most significant. Several recent reports have indicated an increased risk of breast cancer (BC) in girls and young women among HD patients.
In a retrospective multicenter analysis, 63 women treated for HD subsequently developed BC. Results that were obtained in 13 women (21%) who developed either synchronous (five cases) or metachronous (eight cases) BC were analyzed. The median age at diagnosis of HD was 19 years. Seven patients underwent exclusive radiotherapy (RT) (including "mantle" supradiaphragmatic irradiation) and six received concomittant radiation therapy and chemotherapy.
The first breast tumor occurred after a median delay of 16 years. According to the TNM classification, we showed nine stage T0 (non palpable lesions), four stage T1, five stage T2, one stage T3, two stage T4 and five stage Tx BC. Seventeen infiltrating carcinomas, two fibrosarcomas and seven ductal carcinomas in situ were observed. Among 15 axillary dissections performed for invasive carcinomas, histological involvement was found in 10 cases. Seventeen tumors were treated by mastectomy and nine patients underwent conservative surgical treatment. With a 70-month median follow-up (range: 15-125), three patients developed locoregional recurrence and four other metastases. At present, eight are alive with no evidence of disease and one died of intercurrent disease.
According to previous works, BC represents 6.3 to 9% of all second cancers occurring after HD treatment. The risk is higher in young women treated before 20 years of age, especially before 15 years of age. Factors that favour the development of secondary BC are: supradiaphragmatic irradiation, very young age at treatment, chemotherapy with alkylating agents, and probably genetic factors. We conclude that young women and girls treated for HD should be carefully monitored at least 10 years after the end of the treatment for HD, using clinical examination, mammography and ultrasonography. The optimal rythm of this follow-up is not yet clearly defined. Moreover, after multidisciplinary concertation, we suggest that secondary BC be sometimes treated by conservative radiosurgical approach.
Retrospective analysis of results of treatment of 132 subclinical ductal carcinomas in situ, non-palpable.
Patients were treated with limited surgery and 70 Gy radiation therapy (70 Gy).
With a median follow-up of 7 years, the total recurrence rate was 6%, and the actuarial rate at 5 years 4% and at 10 years 13% at. These have no influence on recurrence on the specific actuarial survival rate which was 100% at 10 years. In spite of five infiltrating recurrences of seven, no metastasis appeared 48 months after the salvage surgery. The global rate of breast preservation was 92% at 7 years.
Therapeutic indications were developed taking into account the present analysis and a literature review (2,338 in situ ductal carcinomas, palpable or not, treated with conservative surgery, with or without adjuvant radio-therapy).
Retrospective analysis of 137 patients with limited stage small cell lung carcinoma who received radiotherapy between 1978 and 1990 and literature review.
The population was divided into two groups according to the total dose of radiation delivered to the thorax: 45 Gy (1.8 Gy by fraction) or the equivalent irradiation dose administered by hypofractionation (group 1, 29 patients) and 65 Gy (1,8 Gy by fraction) or the equivalent irradiation dose administered by hypofractionation (group 2, 96 patients).
The actuarial survival rate was 20% at 2 years and 9% at 5 years. It was 25% at 2 years and 17% at 5 years for 12 patients with surgical resection. For patients who did not undergo surgical resection, it was 20% at 2 years and 9% at 5 years for 96 patients belonging to group 2, while it was 14% at 2 years and 3.5% at 5 years for group 1. Deaths due to local relapse reached 48% in the group treated with 45 Gy and 33% in the group treated with 65 Gy (NS). For the 33 patients who were more than 70 years old at the time of treatment, the actuarial survival rate was 18% at 2 years and 6% at 5 years with death from other causes twice as high as that of patients who were less than 70 years old at the time of treatment. For the 59 patients who were less than 70 years old at the time of treatment, in whom supraclavicular node, pleural effusion or superior vena cava syndrome were not depicted and who were treated with the highest dose (4% of the total number of patients), the actuarial survival rate was 20% at 2 years and 14% at 5 years. Literature analysis shows that treatment of limited small cell lung cancer with chemotherapy and thoracic irradiation increased the overall survival rate from 16.5% to 23% at 2 years and the local control from 23% to 48%, in comparison with chemotherapy alone.
Although these results are modest, they seem to be improved with more effective chemotherapy, especially with the association of radiotherapy and concomitant chemotherapy.
To assess retrospectively the long-term results of the combination of surgery and radiotherapy in carcinoma classified cT1.
From 1974 to 1993, 137 women suffering from endometrial carcinoma cT1Nx-0 M0 were entered into the study. The median age was 62 years (range: 39-85 years) and the median follow up was 67 months (range: 0-224 months).
Surgery was performal in 132 women (96.35%). For cT1, the 5-year overall and specific survivals were 81.1% and 84.5%, respectively. The 10-year overall and specific survivals were 68.8% and 82.2%, respectively. Concerning cT1pT1, the 5-year overall and specific survivals, were 83.9% and 87.4%. The 10-year overall and specific survivals were 71.1% and 85%, respectively. Histological grade, pelvic lymph node involvement and myometrial infiltration influence significantly the overall and specific survivals of cT1pT1 tumors. According to multivariate analysis, pelvic lymph node involvement was a powerful prognostic factor for both the overall and specific survivals. If we rule out pelvic lymph node involvement, WHO histological grade was a significant prognostic factor.
Combination of surgery and radiotherapy is still a common procedure for cT1 tumors. When surgery is done before radiotherapy, tailored irradiation may further take place, according to WHO histological grade and pelvic lymph node status.
To evaluate the feasibility of helical tomotherapy intensity-modulated radiotherapy for the treatment of axial and paraspinal tumours.
Fourteen consecutive patients with axial and paraspinal tumours at the Bergonié Institute between June 2007 and June 2009 were analysed. Various localisations were observed: four paravertebral tumours, five primitive vertebral tumours and six iliosacral or sacral tumours.
The dose prescribed to the median of the planning target volume (PTV) varied from 45 to 68Gy depending on histology. The maximum dose delivered to the PTV (Dnear max or D2%) was 60.6Gy (range 46.3-69.1). In the five cases where the tumour was located close to the spinal cord, the median value of Dnear max was 40.1Gy (range 37.8-45.4). In the seven where the tumour was situated close to the cauda equina, the median value of Dnear max was 46.5Gy (range 39.2-60). For two cases in whom the sciatic nerve was the nervous structure at risk, the Dnear max was 64.4 and 67Gy. Six patients were in complete remission, six patients suffered a relapse at a median follow-up of 14.5 months (4-24), two died following local tumour progression and metastasis, tumoral stabilisation had been obtained in two patients. Treatment was well tolerated and was never interrupted in all patients.
Results from this preliminary series are encouraging, particularly concerning the good tolerance of this new intensity-modulated radiotherapy presently more available than proton therapy.
To compare conventional 2D simulation and virtual simulation on 14 patients with breast cancer.
Patients were simulated for treatment using standard procedure. They subsequently underwent CT scan in the treatment position. The CTV was defined as breast tissue. The PTV was obtained by adding a 3D margin of 1 cm around CTV. Organs at risk (lungs and heart) were outlined. Ballistics and dose distribution obtained with the two planning methods were compared.
With conventional simulation, 95% of CTV received 95% of the dose prescribed. Virtual simulation significantly improved dosimetric coverage of PTV without increasing irradiation volume of lung and heart. In 2D simulation, using three slices allowed optimisation by adjusting wedge angle. The five-slice plan was a much better predictor of the maximum dose regions when compared to the three-slice plan. Using entire CT data didn't give any benefit.
Variations in CTV delineation and PTV definition limit interest of virtual simulation. In classic simulation, a 5 CT slice-plan can be used to optimise dose distribution.
Between November 1988 and May 1992, 14 patients were enrolled in a pilot study to evaluate the feasibility and results of hyperfractionated reirradiation for the treatment of head and neck recurrences or of second primary tumors developed in a previously irradiated volume.
All patients underwent a surgical resection for the treatment of their recurrence or second cancer. Reirradiation was proposed because of positive margins and/or lymph node metastasis with extra-capsular spread. The planned reirradiation dose was 60 Gy over 5 weeks, with two daily fractions of 1.2 Gy delivered 6-8 hours apart.
Of the 14 patients, 10 received the reirradiation scheduled dose (ie, 60 Gy). All patients experienced an acute mucositis that never led to disruption of the treatment. Ten patients died 3 to 41 months after reirradiation (mean: 14 months), three were disease-free 48 to 71 months after reirradiation and one was alive with local progressive disease 74 months after reirradiation. The overall local control rate within the reirradiated volume was 43%. The 24- and 36-month overall survival rates were 50 and 35%, respectively. Overall, 13 late complications were noted: four were grade 1, seven were grade 2, and two were grade 3. Three patients still alive in September 1993 and whose initial files were available were enrolled in an additional study to assess from dose-volume histograms the cumulative doses delivered by the two irradiations.
Despite poor local control, reirradiation using a hyperfractionation schedule with high dose level is feasible in terms of acute and late toxicity.
The purpose was to evaluate the use of the CT option for simulator during a 14-month period in the radiotherapy department. The CT option has been adapted on the Philips simulator SL23. The virtual tunnel diameter is 92 cm which allows slice acquisition regardless of the contention device used. This system is connected to the treatment planning system through an Ethernet link. Three fields of view are available which cover the standard radiotherapy use. Four hundred and twenty-seven patients benefited from this system over a 14-month period of use. The number of slices acquired per patient regularly increased. The use of the system was rapidly extended to all the standard treatments. Those slices were also used as additional information for these high technology treatments. The good quality of the images and the reliability of this system involved a rapid integration in the treatment preparation procedure. It will not replace the use of the scanner but will significantly improve the treatment quality.
Despite significant progress in the treatment of glioblastoma, the prognosis of these radioresistant, invasive and hypoxic tumours remain dark. The constant relapse after treatment of this tumour is in part due to its intra-cellular but also micro-environmental radioresistance, largely controlled by growth factors and their receptors. The complexity of the biology of these tumours and the presence of numerous cross-talks between the pathways of these different growth factors can be in part responsible for the negative results obtained in clinical trials associating radiotherapy and targeted drugs designed without previous in vitro and in vivo studies validating the proof of concept of a specific target as key factor of radioresistance. In the aim to optimize the treatment of glioblastoma and to reduce the risks of failure of new trials, several laboratories and clinical departments are developing translational research in radiotherapy and radiobiology, validating in vitro and then in orthotopic xenografts interesting targets, then studying the radiosensitizing effect of targeted drugs directed against these proteins, studying the mechanisms of action and resistance of these drugs, validating these proteins as predictive factors of response to radiotherapy in the patients, and then designing clinical trials, integrating metabolic or functional imaging and surrogate markers to better understand the mechanism of action of these associations. We describe in this article the main translational research axis developed for radiosensitizing glioblastoma, which our lab and department have pursued for several years.
Hypopharyngeal squamous cell carcinoma is associated to one of the most unfavorable prognosis among the cancers of the head and neck. The purpose of this study is to analyze its therapeutic modalities in the Salah-Azaïz Institute (Tunis) and to compare their results.
This retrospective study concerns 271 hypopharyngeal squamous cell carcinomas, compiled in the Carcinologic Surgery Department of Head and Neck of the Salah-Azaïz Institute over a period of 25 years (from 1977 to 2002). The average age of the patients was of 56 years; sex-ratio was on average of 1.2 (man/woman). The indication of a curative treatment was initially retained for 149 (55%) patients, who were the only ones retained for the analysis of results.
We retained the indication of a protocol including surgery and postoperating radiotherapy for 26.2% of the patients. Postoperation mortality rate was 5.1%; the operating rate of morbidity was 46.2%. For 13.5% of the patients, postoperating radiotherapy was permanently interrupted because of a gradual deterioration of the patients' health in the course of treatment. We retained the indication of exclusive radiotherapy for 59.7% of the patients. The average age was of 56 years and the sex-ratio of 1.2. The external radiotherapy was conventional. Radiotherapy had to be permanently interrupted in progress in 32.6% of cases on account of an deterioration of the patients' health; the rate of morbidity of the radiotherapy was 33.3%. We indicated a protocol of conservation of organ with induction chemotherapy for 21 patients (14.1%). The average age was of 53 years (28-65 years) and sex-ratio (man/woman) of 0.5. The global survival was 25.5% at one year, 18.1% at two years, 11.4% at three years and 7.4% at five years. All the patients selected for chemotherapy died in the course of treatment. The rates of survival in two and five years according to protocols surgery-radiotherapy and exclusive radiotherapy were respectively: 21.5 and 12%, and 18.3 and 10%. The difference between the rates of survival of this two protocols is not significant (P =0.08).
Although the induction chemotherapy entails a particularly high death rate in our series, the association surgery-radiotherapy and the exclusive radiotherapy seem to be similarly efficient for the treatment of the hypopharyngeal carcinoma.
- The induction of malignant diseases is one of the most concerning late effects of ionizing radiation. The topic of this study deals with skin tumors developed in the irradiated areas in children given X-ray therapy for tinea capitis.
- All patients with malignant tumors of the scalp referred to Salah Azaiz Institute between 1970 and 2001 have been questioned in order to determine if there had been a prior X-ray irradiation for tinea capitis, its modality, and its consequences. The first scalp irradiation goes back to 1922 and the last was performed in 1963.
- Ninety-eight patients with 150 radio-induced cancers of the scalp following irradiation for tinea capitis are reported (1.5 lesion per patient). The patients were irradiated in various hospitals and dispensaries throughout the country. Eighty-one patients (82%) had only one session of radiation. The average age at irradiation was 12 (+/-6) years, the latent period for radiation-induced skin cancers was 36 (+/-14) years. In 61 patients (62%), the scalp appeared normal and in 38% radiodermatitis was noted. Patient age at diagnosis of malignancy varied from 20 to 83 years with an average of 47 years. Basal cell carcinomas (125 cases) and spinocellular carcinomas (16 cases) were the most common, three other cases of annexial tumors, two malignant non-Hodgkin's lymphomas and four melanoma lesions are also present. Radiotherapy was used for the treatment of 74 patients (alone in 42 and associated with surgery in 32 patients); 14 patients had exclusive surgical excision.
- Basal cell carcinomas are the most frequent tumors arising on chronic radiodermatitis. In spite of the long latency period, patients' young age at irradiation explained the occurrence of these cancers at a relatively young age. Literature review is suggesting recessive mutation of tumor-suppressor genes as the characteristic abnormality in radio-induced cancer.
To review the radiotherapy department experience in treating primary spinal cord ependymomas (PSCE), analyse prognostic factors and provide treatment recommendations regarding literature review.
Sixteen patients with PSCE received postoperative radiotherapy between 1972 and 1997. There were 10 male and 6 female patients with a mean age of 34 years (range 2-63). Surgery was gross total resection in 2 cases, subtotal resection in 9, biopsy in 4 and of unknown type in one patient. All patients were treated with radiotherapy to the craniospinal axis (4 cases), spinal cord (1 case) and to the site of primary tumour in 11 cases.
Five year-survival rate was 73%. Two patients had recurrent tumours within the primary site. Gender, extent of surgery and treatment field extent were not prognostic factors. Histologic type was the only variable predictive of outcome. Patients with myxopapillary type had a 5-year survival rate of 100% compared with 47% for those with other histology types.
We conclude that aggressive surgery is not necessary in the management of PSCE, localised field radiotherapy is associated with favourable outcome, and tumour grade is an important prognostic factor.
To report the epidemiological, clinical aspects and therapeutic results of intracranial ependymomas in Morocco.
Our retrospective study concerned 16 cases of intracranial ependymomas, treated from January 1995 to December 2002 at the radiotherapy department of Ibn Rochd Hospital of Casablanca, Morocco.
The average age was 15 years and complete surgery was possible in two cases. All the patients received cranial radiotherapy, combined with chemotherapy in six cases. Overall survival and progression-free survival at 5 years were respectively 50% and 31%. Eleven patients had local recurrence after an average period of 21 months. Progression-free survival at 5 years was better if complete resection: 100% vs. 28.6% in cases of incomplete resection, and depending on the histological type with 50% for classic ependymomas and 16.6% for anaplastic.
Ependymomas are rare tumors and complete resection is the standard treatment followed by postoperative radiotherapy. The place of chemotherapy remains to be defined.
Adenoid cystic carcinoma represents 1% of head and neck cancers. Adenoid cystic carcinomas are slow growing tumours with high potential for local recurrence. Treatment usually associates radiotherapy and surgery, but the role of radiotherapy remains unclear. We report a retrospective multicentric study of the management and prognostic factors of 169 adenoid cystic carcinomas of head and neck.
Between 1982 and 2010, 169 patients with adenoid cystic carcinoma of the head and neck were referred to the Cercle des oncologues radiothérapeutes du Sud departments of radiotherapy either for primary untreated tumour (n=135) or for a recurrence of previously treated tumour (n=34). The site of adenoid cystic carcinoma was: parotid gland (n=48, 28.4%), minor salivary gland (n=35, 20.7%), submandibular gland (n=22, 13%), sinus cavities (n=22, 13%), other (n=42, 24.9%). Tumour stages were: T1 (12.4%); T2 (14.2%); T3 (12.4%); T4 (41.4%) and Tx (19.5%). Lymph node involvement was 13% and distant metastasis 8.9%. For adenoid cystic carcinomas of the parotid gland, major nerve involvement was evaluated. Preferential site of metastasis was the lung (87.5%). Treatments were: surgery alone (n=27), surgery and adjuvant radiotherapy (n=89), surgery and adjuvant chemoradiotherapy (n=12), exclusive chemoradiotherapy (n=13), exclusive radiotherapy (n=14), other associations (n=5) and no treatment (n=7). Radiotherapy was delivered through photons (n=119), neutrons (n=6), both (n=4). Two patients had a brachytherapy boost. Median prescribed doses to T and N were respectively 65 Gy and 50 Gy for the 119 photons treated patients.
Mean follow-up was 58 months (range 1-250 months). As of December 1, 2010, 83 patients were alive with no evolutive disease (49%), 35 alive and had recurred, 18 had uncontrolled evolutive disease, 28 had died of adenoid cystic carcinoma and 5 of intercurrent disease. Overall survival and disease free survival were respectively 72% and 72% at 5 years, 53% and 32% at 10 years; 5 and 10-year freedom from local recurrence were 81% and 52% respectively. Nerve involvement was found in 17/48 parotid gland adenoid cystic carcinomas. The Cox model including all patients, showed that surgery (P<0.001), surgical margins (P=0.015), nerve involvement (P=0.0079), length of radiotherapy (P=0.018), and tumour location (P=0.041) were associated with disease free survival.
In this large series of adenoid cystic carcinoma of head and neck with a majority of T3-T4 tumours, 10-year survivals were achieved for 50% of patients. Radiotherapy did not impact survival.
In cervix carcinoma: (a) to evaluate the ability of ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the lymph node detection; (b) to investigate the prognostic and predictive value of the primary cervical PET parameters.
Ninety patients treated for cervix carcinoma and evaluated initially by MRI and FGD PET were included. The performances of FDG-PET for lymph node detection (relatively to the lymph node dissection) have been described (sensitivity, specificity, positive predictive value and negative predictive value). PET tumour parameters analyzed were: maximum standard uptake value (SUVmax), the volume and the maximum diameter. The prognostic and predictive values of these parameters were investigated. The tumour response was evaluated on surgical specimens.
PET detected the cervical tumour with a sensitivity of 97% (mean values: SUVmax=15.8, volume=27 mm(3), maximum diameter=47). For the detection of the lymph nodes, the values of sensibility, specificity, positive predictive value and negative predictive value were: 86, 56, 69 and 78% in the pelvic, and 90, 67, 50 and 95% for the para-aortic area, respectively. The SUVmax was correlated with histologic response (P=0.04). The frequency of partial histological response was significantly higher for tumour SUVmax>10.9 (P=0.017). The maximum PET diameter and pathologic response had an impact on disease-free survival and overall survival in multivariate analysis (P<0.05).
PET has high sensitivity in detecting pelvic and para-aortic lymph nodes. Some primary cervical tumour PET parameters are useful as prognostic and predictive factors.
We report on a squamous cell carcinoma of the tongue in a 20-year-old woman with co-infection of the tumor with human papilloma virus type 18 and Epstein-Barr virus. To our knowledge, this is the first case of co-infection in carcinoma of the tongue to be reported. We review the present data and theories concerning viral oncogenesis of oral carcinomas.
To assess usefulness of ((18)F)-fluorocholine positron emission tomography (PET) for localizing relapse in patients with biochemical relapse from prostate adenocarcinoma and its impact on indications of salvage local therapy.
Patients and methods:
An ((18)F)-fluorocholine PET coupled with computed tomography was performed in 28 patients with biochemical progression from prostate adenocarcinoma. At the time of ((18)F)-fluorocholine PET, median prostate specific antigen (PSA) was 3.0 ng/mL (from 0.34 to 93 ng/mL) and 17 patients (60.7%) received hormone therapy. Eighteen patients from this cohort were potentially candidates to salvage radiotherapy.
A pathologic uptake was shown in 11 patients (39.3%) and 17 patients (60.7%) had no pathologic uptake. Median PSA was 2.4 ng/mL (0.33 to 36 ng/mL) in case of negative ((18)F)-fluorocholine PET, versus 6.75 ng/mL (1.21 to 93 ng/mL) in case of pathologic uptake (P=0.04). Among the 17 patients candidates to salvage radiotherapy, ((18)F)-fluorocholine PET helped deciding for salvage radiotherapy in five patients, since it showed only centropelvic pathologic uptake (27.7%). In one patient, it showed metastatic and radiotherapy was contraindicated. After prostatectomy, ((18)F)-fluorocholine PET was positive in only one patient candidate to salvage radiotherapy (9.1%), showing anastomotic relapse.
((18)F)-fluorocholine was positive in about a third of patients with biochemical progression. Its clinical impact is being prospectively investigated.
18 FDG positon emission tomography provides metabolic images and allows better local and metastatic staging than radiologic methods. A best cartography of node involvement and a best delineation of the tumor zone should allow an optimal radiotherapy. Lung cancer is a good example of the interest of this new method.
Between the 4th and 23rd July 1896, Victor Despeignes has performed the first anticancer radiotherapy that has been validated by undeniable publications and practical facts. However, the events and the intellectual approach that led him to perform this unique treatment are misknown. This unpublished biography endeavours to better understand the work of Victor Despeignes who was, first of all, an hygienist physician. The conjunction of Pasteur's ideas, the discovery of X-rays and a probable technical help of the Lumière brothers led him to irradiate a cancerous tumour. The life of Victor Despeignes can be divided in three parts; the Lyon period (1866-1894) during which he became physician and researcher in parasitology, working on the quality of tap water and tuberculosis; the period spent between 1894 and 1907 in Buis-les-Baronnies (Drôme) and thereafter in Les Échelles (Savoie) during which he was a simple district physician and performed the first radiotherapy; the Chambery period (1907-1937) during which he was the Director of the Town Hygiene and provided a major action for public health.
Born in 1870, Claudius Regaud was a pioneer of radiobiology and radiotherapy. As histologist, he developed a new staining technique that allowed him to describe in detail all the reproduction system of a number of animal models. As radiobiologist, he contradicted the interpretations of Tribondeau and Bergonié about relationships between cell proliferation and radiosensitivity. In 1908, he suggested that chromatin was the main target of radiation. As physician, he defined the first bases of anti-cancer radiation treatments and treated patients suffering from incurable cancer from 1911. As military doctor, he organized war hospitals by creating multidisciplinary teams for the surgery of hurts. Organizer, he was one of the founders of the League against Cancer. As radiotherapist and brachytherapist, he contributed to make Institut Curie an international reference center for research and teaching, with nearly a thousand treated patients. As globe-trotter, he was at the origin of the creation of numerous worldwide radiotherapy and radiobiology centers. He died in December 1940 and let an impressive but still misknown scientific heritage. A re-reading of the familial archives and the Regaud Fund of Institut Curie is the occasion to remind the contribution of Regaud.