Michel Caudry

Superior vena cava thrombosis related to catheter malposition in cancer chemotherapy given through implanted ports

Background. Thrombosis of the central veins is one of the most frequent complications of implanted venous access devices. Among the first cases occurring in our patients, most were associated with left‐sided placement of the ports, with catheter tips lying against the external wall in the upper half of the superior vena cava. Some chest radiographs showed lateromediastinal opacities centered on the catheter tip, suggesting a vessel injury. This position allows a narrow contact between the catheter tip and the vessel wall, thus endothelial injuries might result from mechanical and chemical attack.

Preoperative Radiochemotherapy and Sphincter-Saving Resection for T3 Carcinomas of the Lower Third of the Rectum

ObjectiveTo evaluate the complications and oncologic and functional results of preoperative radiochemotherapy and sphincter-saving resection for T3 cancers of the lower third of the rectum. Summary Background DataCarcinomas of the lower third of the rectum (i.e., located at or below 6 cm from the anal verge) are usually treated by abdominoperineal resection, especially for T3 lesions. Few data are available evaluating concomitant chemotherapy with preoperative radiotherapy for increasing sphincter-saving resection in low rectal cancer. MethodsBetween 1995 and 1999, 43 patients underwent preoperative radiochemotherapy with conservative surgery for a low rectal tumor located a mean of 4.5 cm from the anal verge (range 2–6); 70% of the lesions were less than 2 cm from the anal sphincter. There were 40 T3 and 3 T4 tumors. Patients received preoperative radiotherapy with a mean dose of 50 Gy (range 40–54) and concomitant chemotherapy with 5-FU in continuous infusion (n = 36) or bolus (n = 7). Sphincter- saving resection was performed 6 weeks after treatment, in 25 patients by using intersphincteric resection. Coloanal anastomoses were associated with a colonic pouch in 86% of the patients, and all patients had a protecting stoma. ResultsThere were no deaths related to preoperative radiochemotherapy and surgery. Acute toxicity was mainly due to diarrhea, with 54% of grade 1 to 2. Four anastomotic fistulas and two pelvic hematomas occurred; all patients but one had closure of the stoma. Distal and radial surgical margins were respectively 23 ± 8 mm (range 10–40) and 8 ± 4 mm (range 1–20) and were negative in 98% of the patients. Downstaging (pT0–2N0) was observed in 42% of the patients (18/43) and was associated with a greater radial margin (10 vs. 6 mm;P = .02). After a median follow-up of 30 months, the rate of local recurrence was 2% (1/43), and four patients had distal metastases. Overall and disease-free survival rates were both 85% at 3 years. Functional results were good (Kirwan continence I, II) in 79% of the available patients (n = 37). They were slightly altered by intersphincteric resection (57 vs. 75% of perfect continence; NS) but were significantly improved by a colonic pouch (74 vs. 16%;P = .01). ConclusionsThese results suggest that preoperative radiochemotherapy allowed sphincter-saving resection to be performed with good local control and good functional results in patients with T3 low rectal cancers that would have required abdominoperineal resection in most instances.

Intersphincteric resection with excision of internal anal sphincter for conservative treatment of very low rectal cancer

PURPOSE: Standard surgical treatment for low rectal cancer situated below 5 cm from the anal verge or at less than 1 cm from the anal ring is abdominoperineal resection. This is because of the necessity both to achieve a sufficient distal margin and to preserve the whole of the anal sphincter. The aim of this study was to evaluate morbidity, oncologic, and functional results of intersphincteric resection with excision of the internal anal sphincter and low coloanal anastomosis for carcinomas of the anorectal junction. METHODS: From January 1990 to December 1996, 16 patients were studied prospectively. All patients had an infiltrating adenocarcinoma (5 T2 and 11 T3), located between 2.5 and 4.5 (mean, 3.6) cm from the anal verge. Rectal resection with a minimum distal margin of 2 (mean, 2.4) cm was performed in all cases; six patients underwent partial resection of the internal sphincter, and ten patients had a subtotal resection. A colonic J-pouch was associated with coloanal anastomoses in eight cases. Twelve patients had preoperative radiotherapy, 3 with concomitant chemotherapy; 5 patients had postoperative chemotherapy. RESULTS: There was no post-operative mortality. Morbidity occurred in four patients, of whom two underwent permanent colostomy after pelvic hemorrhage or anovaginal fistula. After a median follow-up of 44 (range, 11–92) months, no local recurrence was observed, and two patients died of distal metastases. The five-year actuarial survival rate was 75 percent. Continence was normal in one-half of patients and was altered in the other patients who suffered from occasional minor leaks. The median resting pressure was lower after subtotal than after partial resection of the internal sphincter (40vs. 70 cm H2O;P=0.02), but functional results were similar in the two groups. CONCLUSION: These preliminary results suggest that intersphincteric resection can be an alternative to abdominoperineal resection for selected rectal tumors situated at the anorectal junction, without compromising chance of cure. Functional results and continence were not altered by subtotal resection of the internal anal sphincter.

Fractionated radiation therapy in the treatment of intracranial meningiomas: Local control, functional efficacy, and tolerance in 91 patients☆

PURPOSE To evaluate efficacy and tolerance of external fractionated radiation therapy (RT) in the treatment of intracranial meningiomas. METHODS AND MATERIALS From January 1981 to September 1993, 91 patients with intracranial meningiomas were treated with fractionated RT. Indications were as follows: (a) incomplete surgical resection, 29 patients; (b) tumor recurrences without considering the amount of the second resection, if performed, 14 patients; (c) completely excised angioblastic, aggressive benign, and anaplastic tumors, 8 patients; (d) medically inoperable and basilar tumors where operation would involve considerable danger or permanent neurological damage, 44 patients. Most patients were irradiated with 6 to 9 MV photon beams. A three- to four-field technique with coned-down portals was used. Doses were calculated on the 95% isodose and were given 5 days a week for a median total dose of 52 Gy (1.80 Gy/fraction). RESULTS Median follow-up from radiation therapy was 40 months. Acute tolerance was excellent, but there were six late delayed injuries. Tumor recurrences occurred in six cases. Six patients died from their tumor or RT complications, 19 from nontumoral reasons. Three, 5- and 10-year survival rates were 82, 71, and 40%, respectively. The most significant prognostic factor was age: 5-year survival rate was 86% for patients less than 65 years and 37% for patients more than 65. However, there were no differences in recurrence-free survival rates between patients younger than 65 and the oldest ones. Of 60 symptomatic patients with neurological deficits, 43 had neurological improvement (72%), beginning in some cases within 15 to 20 days after starting RT. CONCLUSION These results reassess the role of fractionated RT in the treatment of meningiomas, and stress on its efficacy, especially on cranial nerves palsies, without severe toxicity in most cases.

Fractionated radiation therapy in the treatment of stage iii and iv cerebello-pontine angle neurinomas: Preliminary results in 20 cases

From January 1986 to March 1989, 20 patients with stage III and IV cerebello-pontine angle neurinomas were treated with external fractionated radiation therapy; seven patients had phacomatosis. Indications for radiation therapy were as follows: (a) poor general condition or old age contraindicating surgery, 10 patients; (b) hearing preservation in bilateral neurinomas after contralateral tumor removal, 5 patients; (c) partial resection or high risk of recurrence after subsequent surgery for relapse, 4 patients; (d) non-surgical relapse, 1 patient. Most patients were irradiated with a 9 MV linear accelerator. A 3 to 4-field technique with 5 x 5 cm portals was used. Doses were calculated on a 95% isodose and were given 5 days a week for a mean total dose of 5140 cGy (180 cGy/fraction). Median follow-up from radiation therapy was 30 months (7 to 46); 4 patients died, 2 with progressive disease. Two patients underwent total tumor removal after radiation therapy (1 stable and 1 growing tumor). On the whole, 14 tumors remained stable, 3 decreased in size, and 3 progressed. CT scan or NMR tumor changes consistent with partial tumor necrosis appeared in four cases. Hearing preservation was obtained in 3/5 hearing patients with phacomatosis. When surgery is not indicated or incomplete, fractionated radiation therapy appears to be an effective and well-tolerated treatment for stage III and IV neurinomas. Hearing can be preserved.

A Randomized Study of Bolus Fluorouracil Plus Folinic Acid Versus 21-Day Fluorouracil Infusion Alone or in Association with Cyclophosphamide and Mitomycin C in Advanced Colorectal Carcinoma

From May 1988 to June 1992, 129 eligible patients suffering from measurable advanced colorectal cancer were enrolled in a randomized study comparing bolus fluorouracil plus leucovorin (FU-FA); continuous fluorouracil infusion (FUcont); FUcont plus Cyclophosphamide and mitomycin C (FUMIC). FU-FA consisted of weekly fluorouracil (FUra) bolus (600 mg/m2) 1 hour after the initiation of a 2-hour infusion of 500 mg/m2 of leucovorin, for 6 weeks every 8 weeks. FUcont patients were planned to receive 400 mg/m2/day FUra infusion, for 21 days every 28 days. In FUMIC patients, FUcont was associated with weekly cyclophosphamide bolus (300 mg/m2) and monthly mitomycin C bolus (10 mg/m2). Quality of life was evaluated using six linear analogue scales, completed by the patient. Accrual in the FUMIC arm was stopped after the 25th patient because of toxicity. The response rates were 22 of 48 (45.8%) with FUcont and 13 of 52 (25%) with FU-FA (P = .048). Progression-free survival (median: 8 v 4.4 months; P = .0026) and overall survival (median: 12.9 v 9.6 months; P = .028) were significantly greater for the FUcont arm compared with the FU-FA arm. Toxicity was observed in 62% of the FUcont patients (grade 3–4: 10%), mainly hand-foot syndrome, diarrhea, mucositis, and mainly gastrointestinal in 69% of the FU-FA patients (grade 3–4: 11.6%). Linear analogue scales exploring quality of life, available for the first 6 months, gave similar scores in FU-FA and FUcont patients. We conclude that this FUcont schedule, achieving high FUra dose-intensity, offers significant advantages, in terms of response and survival, over weekly FUra plus leucovorin.

Effet volume en radiothérapie [II]. Deuxième partie : volume et tolérance des tissus sains

The first part of our work has focused on the relationship between tumor volume and tumor control. Indeed, it is well known that the importance of irradiated volume could be a main parameter of radiation-induced complications. Numerous mathematical models have described the correlation between the irradiated volume and the risk of adverse effects. These models should predict the complication rate of each treatment planning. At the present time late effects have been the most studied. In this report we firstly propose a review of different mathematical models described for volume effect. Secondly, we will discuss whether these theoretical considerations can influence our view of radiation treatment planning optimization.Resume Dans la premiere partie, nous avons evoque la relation entre la taille tumorale et les effets de l’irradiation. Par ailleurs, le volume de tissu sain irradie peut conditionner le risque de complications en radiotherapie. De nombreux modeles mathematiques ont ete appliques a la relation dose–volume–effet afin de predire le risque de complications d’un schema d’irradiation donne. Les modeles les plus developpes concernent les effets tardifs de l’irradiation. Dans un premier temps, pour une meilleure comprehension des mecanismes incrimines dans la relation dose–volume, nous allons faire la revue de la litterature concernant un certain nombre de modeles predictifs. Dans un second temps nous tenterons d’evaluer l’impact de la prise en compte de cet effet volume sur l’optimisation de la planification des traitements par radiations ionisantes.

Radiothérapie fractionnée des méningiomes intracrâniens : 15 ans d'expérience au centre hospitalier universitaire de Bordeaux

PURPOSE: To evaluate the long-term results of external fractionated radiation therapy (RT) in the treatment of intracranial meningiomas. PATIENTS AND METHODS: From January 1981 to December 1996, 156 patients with intracranial meningiomas were treated with external fractionated RT. Median age was 57. Indications for radiation therapy were as follows: (1) completely excised histologically aggressive tumors (12 patients); (2) incomplete surgical resection (37 patients); (3) medically inoperable or basilar tumors where operation would involve considerable danger or permanent neurological damage (77 patients); and, (4) tumor recurrences (30 patients). Most patients were irradiated with 6 to 9 MV photon beams. A three to four-field technique with coned-down portals was used. Since 1993, 71 patients had a three dimensional dosimetry. Doses were calculated on the 95% or 98% isodoses, all fields were treated every day, five days a week, for a median total dose of 50 Gy (1.8 Gy/Fraction). RESULTS: Median follow-up from radiation therapy was 40 months. Acute tolerance was excellent; an early clinical improvement during radiation therapy was noted in 19 patients (17.8%). Clinical improvement or stabilization was observed in 130 patients (83.4%). Radiologically, local control was obtained in 124 cases (79.4%) and tumor recurrences occurred in 21 cases (ten progressions in the treated volume, five borderline, six new locations). Overall and cause specific-survival rates were 75% and 89% at five years, and 45 and 76% at 10 years, respectively. CONCLUSION: These results reassess the role of fractionated RT in the treatment of intracranial meningiomas. Long-term tolerance is excellent for a majority of patients. The study of recurrences confirms the importance of the definition of the target volume, and asks questions about total given doses.

Radiotherapy of gastric cancer with a three field combination: Feasibility, tolerance, and survival

From 1980 to 1984, forty-five patients suffering gastric cancer were irradiated with curative intent. Twenty-three were considered at high risk of recurrence after complete surgical resection (invasion of the serosa, lymph nodes and/or surgical margins); eleven were treated after partial resection, and for eleven others, the local extension precluded surgery. Radiotherapy combined two lateral fields (usually with wedge filters) and an anterior field. The planned dose was 40 to 50 Gy, according to the amount of residual disease and doses delivered to the major part of the liver and the right and left kidneys did not exceed 30, 5, and 18 Gy, respectively. For patients aged less than 71 and whose general condition was acceptable, one cycle of chemotherapy (FAM for 20 patients and 5-FU for 10) preceded irradiation, followed if possible by 6 other cycles. Adverse effects, essentially anorexia, vomiting, and weight loss, led to definitively stopping irradiation in 8 cases, and were present in 21 other patients. Mean weight loss was 2.5 kg. Apart from one patient who developed a subphrenic abcess and died after reoperation, there was neither chronic complication, nor radiation hepatitis or nephritis. For 34 patients, the observation time was superior to 3 years: 23 died of their cancer, 1 of a subphrenic abcess, and 2 of an intercurrent disease. Eight were disease-free at 3 years (three of these were irradiated for macroscopic disease). For the overall series, the 4-year survival rate is 23%. There is a significant survival advantage for females versus males (p less than 0.01), a non-significant tendency in favor of microscopic residual disease versus macroscopic, and no advantage for the combination with FAM compared with no chemotherapy (non-randomized). This technique appears feasible with an acceptable tolerance and can control local tumor in a few cases. The planned dose of 40 Gy was probably too small and we are now testing 45 Gy delivered over the large initial volume, and boosts of 10-15 Gy to residual disease.

Results of surgical treatment of T3 and T4 tumors of the oral cavity and oropharynx

The combined use of surgery and radiotherapy is commonly accepted as the most effective treatment for locally advanced head and neck cancers. T3 and T4 tumors of the oral cavity and oropharynx often necessitate extensive local surgery. From 1981 to 1988, 199 patients with T3 and T4 tumors of the oral cavity and oropharynx were treated. One hundred seventeen patients underwent surgery plus postoperative radiotherapy; 78 had flap reconstructions. This series is extremely homogeneous because surgery was always performed by two surgeons, whereas radiotherapy was the responsibility of the same physician. The results of this study show a 96% local control rate at the end of treatment among the patients with combined treatment. The average time by which hospitalization was prolonged due to surgery was 29 days. The type and delay of recurrences and survival in relation with node involvement are also discussed. Extensive surgery in association with radiotherapy remains a reliable treatment in such patients.