Biomedical subjects
Publications and source records attributed to D Peiffert.
Brachytherapy in velo-tonsillar region is not applied in all the institutions because of difficulties to learn it. For the implantation of wires in the soft palate, the Reverdin needle is replaced by a curved guide of angiocatheter 14 Gauge. This technique is easy and reduces the risk of tear mucosa.
INTRODUCTION: Despite improvements in surgical techniques and perioperative mortality, only slight improvements in the 5-year survival of patients with esophageal cancer have been observed in the last 20 years. Many patients with apparently localized cancer will have recurrences or metastatic disease despite surgery with curative resection. Consequently, multimodal therapies, including chemotherapy and radiotherapy, were introduced. This review outlines and critically analyzes current non-surgical treatments, including palliative care. CURRENT KNOWLEDGE AND KEY POINTS: Esophageal cancers appear to be chemosensitive but the median duration of response is short and toxicity consistent, especially in metastatic disease. Consequently, palliative chemotherapy should be offered preferably within a clinical trial. Chemotherapy as the only adjuvant treatment cannot be recommended outside clinical trials. Radiotherapy alone as a curative treatment has been proven to be inferior to chemoradiotherapy in inoperable tumors. Some data support the use of preoperative chemoradiotherapy, but randomized trials are conflicting. A pathological complete response has been identified as a favorable prognostic factor for survival. Self-expanding esophageal metal stents are a simple and effective palliative treatment of malignant dysphagia and can be considered as the reference treatment in patients with obstruction of the lower esophagus or with fistula. FUTURE PROSPECTS AND PROJECTS: Taxanes should be evaluated in randomized studies using chemotherapy or chemo-radiotherapy. Progress in radiotherapy, such as accelerated fractionation, greater radiation dose, and the addition of brachytherapy, will increase locoregional control and probably survival. The role of secondary surgery in patients responding to chemoradiotherapy still needs to be answered.
BACKGROUND AND PURPOSE: To evaluate the feasibility of pulsed dose rate (PDR) brochytherapy in squamous cell anal canal carcinoma (SCACC). MATERIALS AND METHODS: In this study a series of 19 patients with SCACC were included between 1995 and 1997. All patients were treated with curative intent with external beam radiotherapy (EBRT) (44-50 Gy) and one or two cycles of concomitant fluorouracilcisplatinum. After a gap of 2-3 weeks PDR interstitial brachytherapy was performed with a rigid needles technique. The dose was between 10-25 Gy (PARIS system). RESULTS: All patients are alive. No severe grade 3-4 toxicity was encountered. One local relapse one metastatis were seen in two distinct patients. There was no dysfunction of the after loading machine. CONCLUSION: The feasibility of PDR brachytherapy appears good in SCACC. It is an attractive alternative to low dose rate brachytherapy.
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PURPOSE: To evaluate the prognostic value of tumor downstaging after preoperative radiation for resectable rectal cancer. METHODS AND MATERIALS: Eighty-eight patients with non-metastatic resectable rectal cancers (76 T3 and 12 T4) were treated with preoperative irradiation. Median dose was 40 Gy (30-46 Gy) delivered over 32 days (range 11-40). Seventeen patients received preoperative chemotherapy, two courses of 5-fluorouracil (5FU) 350 mg/m2/day and folinic acid 20 mg/m2/day; 5 days per week during the first and fifth weeks of radiotherapy. Surgery was performed with a mean delay of 46 days after completion of irradiation and included 66 abdominoperineal resections and 22 anal sphincter-preserving procedures. Postoperative chemotherapy was administered in 44 patients. RESULTS: Histological tumor stages were: complete histological response in 7%, pT2N0 in 19%, pT3N0 in 46%, and pT2-3N1 in 28%. Tumor downstaging occurred in 26%. No predictive factor of downstaging was statistically significant. The median follow-up was 33 months. The 3- and 5-year cancer-specific survival rates were 100% for the pT0N0 and pT2N0, respectively, 89% and 68% for pT3N0, and 64% and 0% for pT2T3N1. After preoperative irradiation, the pathological tumor stages remained a prognostic factor. Patients with downstaging (pT0T2N0) had significantly higher cancer-specific survival rates than the group without downstaging: 100% and 80% at 3 years, and 100% and 45% at 5 years; respectively (p = 0.011). The 3- and 5-year recurrence free-survival rates were 94% for the group with downstaging and 56% and 50%, respectively, for the group without downstaging (p = 0.002). CONCLUSION: Downstaging after preoperative irradiation in this retrospective study results in an improvement in local control and survival.
PURPOSE: From 1975 to 1996, 98 patients with infiltrative vesical carcinomas were treated at the Centre Alexis Vautrin by conservative surgery and interstitial brachytherapy (192lr). The mean follow-up was about eight years. From this retrospective non randomized study, we tried to determine the tolerance to this treatment. MATERIALS AND METHODS: There were 86 men and 12 women. The mean age was 63 years. We found three pTis tumors, 28 stage pT1 tumors, 38 stage pT2 tumors, 24 stage pT3A tumors, four stage pT3B tumors and one stage Tx tumors. The therapeutic scheme consisted of pelvic radiation therapy (3 fractions of 3,5 Gy) immediately followed by lymphadenectomy (for stage pT3 tumors) and by cystotomy or partial cystectomy during which we inserted brachytherapy plastic tubes. The delivered dose was 50 Gy for superficially infiltrative tumors and 30 Gy for deeply infiltrative tumors; at the lowest dose, the treatment ended with external beam irradiation. RESULTS: At 5 years the control rate was 72%, the specific survival 80% and the global survival 71%. Twenty-nine patients had a local recurrence. Of these, seven underwent total cystectomy. Thirty-seven patients developed 43 complications; 35 were intravesical, 10 (28%) were estimated to be higher than grade 2 because of technical problems that led us to modify the technique. CONCLUSION: It is essential to develop close collaboration between surgeons and brachytherapists, to select patients and to use a rigorous technique. Interstitial brachytherapy for infiltrative vesical carcinomas thus yields both high local control and satisfying results in regard to patient's well-being.
PURPOSE: The detection of an infraclinical primary by tonsillectomy in case of cervical lymph node of an epidermoid carcinoma with unknown primary after a radical neck dissection, allows avoiding irradiation of the normal larynx. The aim of this study is to quantify the rate of tonsil primary to justify this procedure. METHODS AND MATERIALS: From 1969 to 1992, 87 patients had a tonsillectomy as part of the workup for cervical nodal metastasis of an epidermoid carcinoma with unknown primary. The mean age was 57 years (range: 39-75 years) and the sex ratio was 8.6. Sixty-seven patients had a single cervical adenopathy (17 N1, 30 N2a, 5 N3, 15 Nx), and 20 patients multiple cervical adenopathies (17 N2b, 3 N2c). The treatments included always an irradiation to the node areas (50 Gy), and to the pharyngolarynx in case of normal tonsil (50 Gy), or to the tonsil if it was the primary (50 Gy with a brachytherapy boost of 20-25 Gy). In this last case, the larynx could be protected. RESULTS: Tonsillectomy never induced specific complication. Out of 87 patients, 26% had a tonsil primary. There was not specific histological differentiation in this group. In the 67 patients with a single cervical adenopathy, 31% had a tonsil primary (6 N1, 7 N2, 1 N3, 7 Nx). It was a subdigastric adenopathy in 38%, a submandibular in 28% and a midjugulocarotidian in 23%. Among the 17 patients N2b, none had a tonsil primary. In the three patients N2c, two presented a tonsil carcinoma (two subdigastric nodes). CONCLUSION: Tonsillectomy allows avoiding irradiation of normal larynx in 26% of patients who have a cervical lymph node with unknown primary. It should be performed in case of a single node of the subdigastric, midjugulocarotidian or submandibular area or bilateral subdigastric adenopathies.
PURPOSE: Few series have described treatment results of anal margin tumors as defined in the UICC 87 classification. The purpose of this article is to describe experience with an uncommon condition in a single cancer center. METHODS AND MATERIALS: From 1971 to 1995, 32 patients with carcinoma of the anal margin were irradiated with a curative intent, and 31 were followed-up for more than 6 months (mean = 4.5 years). There were 9 T1, 15 T2, 7 T3, and 1 T4 (vulvar), with 26 N0 and 6 N1. There was a minor invasion of the lower canal in 17 patients. The histological types were 24 squamous cell and 7 basocellular carcinomas, and 1 Paget's disease. The treatment was a combined External Beam Irradiation (EBI) and Brachytherapy (BT) in 16 patients, an exclusive BT in 12 patients, and an exclusive EBI in 4 patients. No prophylactic inguinal irradiation was delivered. RESULTS: The 5-year actuarial results are as follows: overall survival = 67%, specific survival = 89%. The only prognostic factor was nodal involvement (p < 0.001). T-stage, T-size, age, sex, and treatment schedule were not significant. The overall local control was 77%, and 93.5% after salvage. Two N0 patients relapsed in inguinal areas (one was salvaged). Twenty-six percent presented a Grade 3 or 4 late complication, necessitating a temporary colostomy in only one patient. The sphincter conservation reached 84% for the whole series, 80% for patients followed-up 5 years or more, and 89% for cured patients. CONCLUSION: Results are similar to other series, and seem better than for anal canal cancer. We recommend exclusive irradiation. There is no data recommending concomitant chemotherapy. Depending on the tumor size and localization, the tumor boost can be applied by EBI or BT. Surgery is reserved for small tumors far from the canal or for salvage. An inguinal prophylactic bilateral irradiation should be recommended for N0, with tumors over 4 cm.
PURPOSE: To study the rate and severity of complications in a series of 1134 patients treated by definitive irradiation for tumors of the oral cavity (772 cases) or the oropharynx (361 cases). METHODS AND MATERIALS: Patients were staged as 29.5% T1, 42% T2, 26% T3, 2.5% T4-Tx, and 74.5% N0 tumors. We treated 364 patients with brachytherapy only (192Ir) for the primary lesion. External irradiation and brachytherapy were combined for 770 patients. RESULTS: The results included local control and survival. Out of 1134 patients, 330 had 376 complications. Grade 1 complications occurred in 20% of the patients, Grade 2 in 9%; Grade 3 in 4%; and Grade 4 in 0.2%. Of the Grade 1 complications, 78% were soft tissue and only 24% were bone complications. For the more severe grades (2, 3, and 4), there were 56 soft tissue complications and 90 bone complications out of 1340 patients. The statistical analysis included tumor-related factors and treatment-related factors. For the first two factors, only tumor location was significant. The treatment-related factors significant for complications were studied in univariate and multivariate study. This multivariate study confirmed that for soft tissue complications dose rate and volume treated were important (p < 0.001). It also confirmed that for bone complications, total dose > 80 Gy, dose rate > 0.7 Gy/h, and the absence of leaded protection of the mandible were all important factors. CONCLUSION: This statistical study should allow future reduction of severe complications (Grades 2, 3, 4), if treatment factors inducing them can be taken into account. This is not always possible for very large tumors.
UNLABELLED: We analyzed in a retrospective series of patients treated by conservative irradiation for an epidermoid cancer of the anal canal (ECAC) the prognostic factors of locoregional control (LRC), survival, late severe complications (LSC), and sphincter conservation (SC). METHODS AND MATERIALS: From 1976 until 1994, 118 patients presenting with an ECAC were conservatively treated (mean age, 65 years). According to the 1987 International Union Against Cancer (TNM) classification, they were: 19 T1, 70 T2, 22 T3, 7 T4, 94 N0, and 24 N1-3. The treatment started with external beam irradiation (EBI) (36 Gy in 3 weeks or 45 Gy in 5 weeks). Concomitant chemotherapy (5-fluorouracil and mitomycin C) was delivered to 31 patients. Two months later, a boost of 20 Gy was delivered by interstitial 192Ir brachytherapy to 101 patients and EBI in 5. Twelve other patients had an abdominoperineal resection (APR). The mean follow-up was 6 years. RESULTS: At 5 years the overall survival was 60%, and specific survival (SS) was 75%; it was 94% for T1, 79% for T2, 53% for T3, and 19% for T4. In multivariate analysis, tumor size (> or = 4 cm), node involvement, and no response to the EBI were factors of poor prognosis for SS. Thirty-two locoregional recurrences occurred of which 21 were local recurrences in the 106 patients treated by a conservative schedule. Only tumor size and response to the EBI were prognostic factors on multivariate analysis for local and LRC. A total of 17 patients presented with LSC (Grade 3, 16 patients; and Grade 4, 1 patient), which was treated by APR in 4 patients and colostomy in 11 (of which 7 were definitive). The only significant prognostic factor for LSC in the multivariate analysis was the total extrapolated response dose of irradiation. The definitive rate of SC after conservative treatment in cured patients was 100% for T1, 82% for T2, 58% for T3, and 100% for T4. Since 1989, improvements of the technique have allowed reduction of the LSC in maintaining the same local control. CONCLUSION: The results of this series are similar to those of the literature. The confirmation of pretherapeutic prognostic factors related to response to the treatment should allow us to adapt the therapeutic intensity for each case to obtain better tumor control, with as few sequelae as possible, to yield a better rate of SC.
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PURPOSE: We wanted to study the influence of the time factor in a combination of external irradiation and brachytherapy from a retrospective study of 370 squamous cell carcinomas of soft palate and tonsil. PATIENTS AND METHODS: From 1977 to 1993, 370 soft palate and tonsillar carcinomas were treated at the Centre Alexis Vautrin. All patients received external irradiation (ERT) with a minimum dose to the tumour of 45 Gy, followed by low dose rate brachytherapy by Iridium 192 using the technique of plastic tubes; 22 patients received neo-adjuvant chemotherapy. We treated 85 T1, 159 T2, 117 T3 and nine T4 or TX carcinomas; 128 of these had palpable nodes. There were 267 men and 24 women. The median age was 55 years (range 33-81 years). RESULTS: The median duration of the total treatment was 57 days. The rate of local control was 88% at 5 years when the treatment time was 7 weeks and 74% when it was 9 weeks (P = 0.001). The rates of overall survival at 5 years were 63 and 44%, respectively (P < 0.0001). For the interval between external irradiation and brachytherapy the series was divided into three groups, i.e. patients treated with a delay inferior or equal to 16 days (2 weeks), patients for which the interval was between 16 and 20 days and patients treated with a delay greater than 20 days (3 weeks). The rates of local control and overall survival at 5 years were not significantly different in the two first groups so we amalgamated these two groups and compared them with the third group. In this way the time cut-off for the delay between external irradiation and brachytherapy was 20 days. At 5 years, the rate of local control was 85% for the group for which the interval was inferior to 3 weeks and 73% when the delay was greater (P = 0.01). The rates of overall survival at 5 years were 59 and 38%, respectively (P < 0.001). Multivariate analysis confirmed that protraction of treatment was a factor for poorer local control. This factor was independent of the other prognostic factors. CONCLUSION: The total duration of irradiation and the delay between external irradiation and brachytherapy were significant prognostic factors for local control and overall survival of soft palate and tonsil carcinomas. The overall duration should not be greater than 7 weeks (external irradiation, 5 weeks plus a delay of 12-15 days between ERT and brachytherapy). The delay should never be greater than 20 days, but a boost should be considered to make up for the loss of local control.
BACKGROUND AND PURPOSE: Although supracervical hysterectomy is becoming a rare procedure, there are still many women with retained cervical stump. The purpose of this retrospective study was to assess the results of treatment in patients with carcinoma of the cervical stump. MATERIALS AND METHODS: From 1974 to 1990, 77 patients were treated for an infiltrating carcinoma of the cervical stump. This group accounted for 6.6% of the cervical carcinoma diagnosed during the same period. The pathological examination showed, 91% of squamous cell carcinomas and 9% of adenocarcinomas. FIGO stage distribution was: I (35%), II (45%), III (18%), IV (2%). According to the stages, the treatment used a combination of external beam radiation therapy (EBRT) with plesiobrachytherapy (PBT), and in a few cases, patients underwent surgery or interstitial brachytherapy (IBT). In patients with bulky tumour or advanced stage and/or lymphatic node involvement, EBRT was first delivered. Most of Stage I and Stage II patients, began their treatment with PBT. All stages included, 95% of the patients were treated by exclusive radiation therapy. Complications were classified according to the recommendations of late effects normal tissues (LENT) scoring system described by the EORTC/RTOG. RESULTS: Three-year pelvic control was achieved in 59 of 77 patients (76.6%) in the whole series. Three-year pelvic control probabilities were 77% (95% CI: 66-85%), and 89% (95% CI: 72-96%), 73.7% (95% CI: 65-88%) and 56% (95% CI: 28-80%) in the whole series and in Stage I-III tumour patients, respectively. The 5-year and 10-year overall survival probabilities in the whole series, were 66.4% (95% CI: 55-76%) and 61.2% (95% CI: 50-72%), respectively. Ten patients (12.8%) developed 17 late complications distributed as follows: G1, nine patients (11.7%); G2, five patients (6.5%); G3, one patient (1.3%); and G4, two patients (2.6%). CONCLUSIONS: Treatment results are similar both in patients with carcinoma of the cervical stump and in patients with carcinoma of the intact uterus. Indeed, it is sometimes difficult to perform a correct PBT application because of the pelvic anatomic modifications induced by the subtotal hysterectomy and its consequences on the new organisation of critical organs into the treated volume.
The aim of this study was to analyse the role of post-operative brachytherapy (BT) in a group of patients with a high risk of local relapse (positive or narrow surgical margins) for squamous cell carcinoma of the mouth floor (SCCFM). A comparison with post-operative external beam irradiation (EBI) in a group of patients with standard risk of local relapse for SCCFM with free margins is performed to estimate the benefit of BT. From 1979 to 1992, an initial group of 32 patients with SCCFM (12, T1-2; 20, T3-4x) received an Ir 192 low dose rate BT using plastic tubes (+EBI for 20 patients) after surgery with positive or close margins. BT was applied in one or two planes to the surgical scar. The mean dose of BT was 57 Gy (range: 50-60) for exclusive BT and 22 Gy (range: 15-30) when a boost was applied (mean EBI dose = 50 Gy). During the same period, 36 patients had post-operative external irradiation alone after satisfactory surgical resection. Excluding the post-operative margin, these two groups were comparable for other prognostic factors. The mean follow-up was 46 months (range: 5-145) with a minimum follow-up of 2 years. For BT and EBI groups, the 5-year results (Kaplan-Meier) were, respectively, overall survival 62% and 43%, local control 81% and 60% (P = 0.09) (log-rank) and severe complications 4/32 and 1/36. Post-operative BT achieves good local control for patients with narrow or positive margins by increasing the dose to the surgical scar, with good tolerance. Given these encouraging results, we confirm this treatment for these patients.
Brachytherapy has confirmed its prevailing role in conservative treatment of oral cavity carcinomas. To describe late toxicity in long-term surviving patients, comparisons with other series are necessary. Study of series of patients implanted for floor of the mouth or mobile tongue shows the need for more detailed data. Dental prophylaxy and lead protection of the mandibule, good indications and techniques of brachytherapy are necessary to avoid late complications. Some treatment factors have proved to be of good prognosis for late complications through multivariate analysis of large series treated with lr 192 wires, using the Paris system, eg, dose rate lower than 0.5 or 0.7 Gy/h, intersource spacing smaller than 1.2 or 1.5 cm, treated surface less than 12 cm2, lineic activity less than 1.5 mCi/cm, less than 1 cm diameter hyperdose, and use of mandibular lead protections. Tumor volume and location to the floor of mouth lead to higher risk of complications. Knowledge of treatment-related factors is important, with the development of new afterloading projectors allowing to control the dose rate and correct small inhomogeneities. High-dose rate exclusive brachytherapy is not recommended. More precise and reproducible classification should be used to report complications in series leading to publications in the future, thus allowing to compare results, reduce complication rates and improve the quality of life.
BACKGROUND: Chemotherapy (5-fluorouracil-mitomycin C) concomitant with radiotherapy (RT) increases local control and colostomy-free survival in advanced anal canal carcinomas (ACC). The purpose of this prospective trial was to analyse the toxicity of and response to an induction chemotherapy combining 5-fluorouracil (5-FU) and CDDP administered concomitantly with irradiation. PATIENTS AND METHODS: Thirty patients (24 F/6 M, mean age 60, range 38-74) with an advanced ACC > 40 mm and/or with node involvement were prospectively treated (1 T1, 16 T2, 8 T3, 5 T4, 10 N1, 1 N2, 8 N3) from November 1994 to January 1996. Two induction and two concomitant cycles of 5-FU (800 mg/ m2 D1-4 infusion) and CDDP (80 mg/i.v./m2 at D1) were delivered. RT consisted of 45 Gy (1.8 Gy/fr, 5 fr/w) on pelvis +/- inguinal nodes or 30 Gy (3 Gy/fr, 4 fr/w) by direct perineal field. A boost (15-20 Gy) was delivered six weeks later. RESULTS TOXICITY: one patient died of a pulmonary embolism on D4. The remaining 29 received the entire treatment, with reduced 5-FU doses in 11 patients because of acute toxicity. The RT boost was delayed for one patient (aplasia). In 109 cycles, 3 grade 4 and 17 grade 3 toxicities were observed; there were no toxic deaths. Tumor response: the complete response (CR) and partial response (PR) rates were, respectively, 11% and 61% after induction chemotherapy, 59% and 31% after concomitant radiochemotherapy and 96% and 0% two months after completion of the treatment. No tumor progression was observed. CONCLUSION: the treatment was well tolerated and there was good compliance. After induction chemotherapy, most of the patients were in PR, with some even in CR. After completion of the treatment all but one were in CR. The tumor response and the long term results of 50 patients will be analysed before initiation of a randomised trial is considered.
PURPOSE: To investigate the potential gain of the concomitant use of radiotherapy and chemotherapy in improving local control and reducing the need for colostomy, a randomized phase III trial was performed in patients with locally advanced anal cancer. MATERIALS AND METHODS: From 1987 to 1994, 110 patients were randomized between radiotherapy alone and a combination of radiotherapy and chemotherapy. The patients had T3-4NO-3 or T1-2N1-3 anal cancer. Radiotherapy consisted of 45 Gy given in 5 weeks, with a daily dose of 1.8 Gy. After a rest period of 6 weeks, a boost of 20 or 15 Gy was given in case of partial or complete response, respectively. Surgical resection as part of the primary treatment was performed if possible in patients who had not responded 6 weeks after 45 Gy or with residual palpable disease after the completion of treatment. Chemotherapy was given during radiotherapy: 750 mg/m2 daily fluorouracil as a continuous infusion on days 1 to 5 and 29 to 33, and a single dose of mitomycin 15 mg/m2 administered on day 1. RESULTS: The addition of chemotherapy to radiotherapy resulted in a significant increase in the complete remission rate from 54% for radiotherapy alone to 80% for radiotherapy and chemotherapy, and from 85% to 96%, respectively, if results are considered after surgical resections. This led to a significant improvement of locoregional control and colostomy-free interval (P = .02 and P = .002, respectively), both in favor of the combined modality treatment. The locoregional control rate improved by 18% at 5 years, while the colostomy-free rate at that time increased by 32% by the addition of chemotherapy to radiotherapy. No significant difference was found when severe side effects were considered, although anal ulcers were more frequently observed in the combined-treatment arm. The survival rate remained similar in both treatment arms. Skin ulceration, nodal involvement, and sex were the most important prognostic factors for both local control and survival. These remained significant after multivariate analysis. The improvement seen in local control by adding chemotherapy to radiotherapy also remained significant after adjusting for prognostic factors in the multivariate analysis. Event-free survival, defined as free of locoregional progression, no colostomy, and no severe side effects or death, showed significant improvement (P = .03) in favor of the combined-treatment modality. The 5-year survival rate was 56% for the whole patient group. CONCLUSION: The concomitant use of radiotherapy and chemotherapy resulted in a significantly improved locoregional control rate and a reduction of the need for colostomy in patients with locally advanced anal cancer without a significant increase in late side effects.