Judith Huart

Combined radiation and chemotherapy for invasive transitional-cell carcinoma of the bladder: a prospective study

PURPOSE To improve the results obtained by cystectomy alone and to determine the possibilities of conservative treatment in invasive bladder cancer, we designed a prospective study using a combination of fluorouracil (5-FU) plus cisplatin and concomitant radiation therapy, followed by either cystectomy or additional chemoradiotherapy. PATIENTS AND METHODS Fifty-four patients with stage T2 to T4 operable untreated invasive bladder cancer were entered onto the study. Treatment was begun in all patients by transurethral resection (TUR) and followed by the 5-FU-cisplatin combination with concomitant bifractionated split-course radiation therapy. A control cystoscopy was performed 6 weeks after completion of the neoadjuvant program. Patients with persistent tumor underwent cystectomy. Complete responders were treated by either additional chemoradiotherapy (group A) or cystectomy (group B). RESULTS At control cystoscopy, 40 of 54 patients (74%) had a histologically documented complete response. Four responders developed recurrent pelvic disease after a mean follow-up time of 27 +/- 12 months (three in group A and one in group B). Metastatic disease, which developed in 16 patients, occurred more frequently in the nonresponders (71%) than in responders (15%). The disease-free survival rate at 3 years was 62%; it was significantly better in responders (77%) than in nonresponders (23%). There was no difference in survival between groups A and B. CONCLUSION This neoadjuvant chemoradiotherapy combination, easy to implement and well tolerated even in elderly patients, provides a high complete response rate. It may prove to be effective in inoperable patients and may be proposed as conservative treatment in patients with a complete response to the initial course of chemoradiation.

Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer

PURPOSE To identify predicting factors for local failure and increased risk of distant metastases by statistical analysis of the data after breast-conserving treatment for early breast cancer. METHODS AND MATERIALS Between January 1976 and December 1993, 528 patients with nonmetastatic T1 (tumors < or = 1 cm [n = 197], >1 cm [n = 220]) or T2 (tumors < or = 3 cm [n = 111]) carcinoma of the breast underwent wide excision (n = 435) or quadrantectomy (n = 93) with axillary dissection (negative nodal status [n-]: 396; 1-3 involved nodes: 100; >3 involved nodes: 32). Radiotherapy consisted of 45 Gy to the entire breast via tangential fields. Patients with positive axillary lymph nodes received 45 Gy to the axillary and supraclavicular area. Patients with positive axillary nodes and/or inner or central tumor locations received 50 Gy to the internal mammary lymph node area. A boost dose was delivered to the primary site by iridium 192 Implant in 298 patients (mean total dose: 15.2+/-0.07 Gy, range: 15-25 Gy) or by electrons in 225 patients (mean total dose: 14.8+/-0.09 Gy, range: 5-20 Gy). The mean age was 52.5+/-0.5 years (range: 26-86 years) and 267 patient were postmenopausal. Histologic types were as follows: 463 infiltrating ductal carcinomas, 39 infiltrating lobular carcinomas, and 26 other histotypes. Grade distribution according to the Scarff, Bloom, and Richardson (SBR) classification was as follows: 149 grade 1, 271 grade 2, 73 grade 3, and 35 nonclassified. The mean tumor size was 1.6+/-0.3 cm (range: 0.3-3 cm). The intraductal component of the primary tumor was extensive (EIC = IC > or = 25%) in 39 patients. Tumors were microscopically bifocal in 33 cases. Margins were assessed in the majority of cases by inking of the resection margins and were classified as positive in 13 cases, close (< or = 2 mm) in 21, negative (>2 mm tumor-free margin) in 417, and indeterminate in 77. Peritumoral vascular invasion was observed in 40 patients. Tamoxifen was administered for at least 2 years in 176 patients. At least six cycles of adjuvant systemic chemotherapy were administered in 116 patients. The mean follow-up period from the beginning of the treatment was 84.5+/-1.7 months. RESULTS First events included 44 isolated local recurrences, 8 isolated axillary node recurrences, 44 isolated distant metastases, 1 local recurrence with synchronous axillary node recurrence, 7 local recurrences with synchronous metastases, and 2 local recurrences with synchronous axillary node recurrences and distant metastases. Of 39 pathologically evaluable local recurrences, 33 were classified as true local recurrences and 6 as ipsilateral new primary carcinomas. Seventy patients died (47 of breast carcinoma, 4 of other neoplastic diseases, 10 of other diseases and 9 of unknown causes). The 5- and 10-year rates were, respectively: specific survival 93% and 86%, disease-free survival 85% and 75%, distant metastasis 8.5% and 14%, and local recurrence 7% and 14%. Mean intervals from the beginning of treatment for local recurrence or distant metastases were, respectively, 60+/-6 months (median: 47 months, range: 6-217 months) and 49.5+/-5.4 months (median: 33 months, range: 6-217 months). After local recurrence, salvage mastectomy was performed in 46 patients (85%) and systemic hormonal therapy and/or chemotherapy was administered to 43 patients. The 5-year specific survival rate after treatment for local recurrence was 78+/-8.2%. Multivariate analysis (multivariate generalization of the proportional hazards model) showed that the probability of local control was decreased by the following four independent factors: young age (< or = 40 yr vs. >40 yr; relative risk [RR]: 3.15, 95% confidence interval [CI]: 1.7-5.8, p = 0.0002), premenopausal status (pre vs. post; RR: 2.9, 95% CI: 1.4-6, p = 0.0048), bifocality (uni- vs. bifocal; RR: 2.7, 95% CI: 2.6-2.8,p = 0.018), and extensive intraductal component (IC <25% vs. IC > or = 25%; RR: 2.6, 95% CI: 13-5.2, p = 0

Successful treatment of radiation-induced fibrosis using liposomal Cu Zn superoxide dismutase: clinical trial

Based on experimental and clinical evidence indicating that the anti-oxidant agent liposomal Cu/Zn superoxide dismutase (Lipsod) is an effective anti-inflammatory drug and possibly might be effective in reducing late radiation-induced tissue injury, a clinical trial using Lipsod to treat long-standing radiation-induced fibrosis (RIF) was begun at the Necker Hospital, Paris in May 1984. Thirty-four patients presenting 42 distinct palpable zones of RIF involving the skin and underlying tissues were treated from May 1984 to January 1986 and followed for an average of 5 years (range, 14-89 months). Lipsod was administered over 3 weeks in twice weekly i.m. injections of 5 mg for a total of 30 mg. Patients underwent two physical examinations by independent physicians at each check-up. Parameters noted included determination of the density of the palpated fibrotic block and the dimensions of the projected cutaneous surface. The extent of change in the fibrotic zone was expressed as the ratio of the sum of the dimensions (L + W) and the ratio of the uncorrected areas (L x W) of the projected cutaneous surface before and after treatment. Changes in density were noted and scored. All patients showed some clinical regression of fibrosis. In most patients, clinically assessable regression begun during the third week of treatment and was maximum by 2 months. The mean decreases in the linear dimensions (L + W) and in the area (L x W) of the projected cutaneous surface were 41 +/- 30% and 57 +/- 26%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Linac radiosurgery for cerebral arteriovenous malformations: results in 169 patients

PURPOSE To present the SALT group results using Linac radiosurgery (RS) for AVM in 169 evaluable patients treated from January 1990 thru December 1993. METHODS AND MATERIALS Median age was 33 years (range 6-68 years). Irradiation was the only treatment in 55% patients. Other treatment modalities had been used prior to RS in 45%: one or more embolizations in 36%, surgery in 6%, and embolization and surgery in 3% patients. Nidus were supratentorial in 94% patients, infratentorial in 6% patients. Circular 15 MV x-ray minibeams (6-20 mm) were delivered in coronal arcs by a GE-CGR Saturne 43 Linac. Patient set-up included a Betti arm-chair, a Talairach frame. Prescribed peripheral dose was 25 Gy on the 60%-70% isodose (max dose 100%). Arteriographic results were reassessed in December 1997 at 48 to 96 months follow-up. RESULTS The overall obliteration rate (OR) was 64% (108/169). AVM volumes ranged from 280 to 19,920 mm(3), median 2460 mm(3). OR was 70% for AVM </= 4200 mm(3) 4200 mm(3) (p 25 mm (p = 0.04). OR was 71%, in the absence of embolization, vs. 54% for previously embolized nidus (p = 0.03). OR was 71% for monocentric RS vs. 54% for multi-isocenters (p 28 Gy vs. 55% for values </= 28 Gy (p 79% vs. 57% for lower values (p 17 Gy, vs. 59% for mLd </= 16 Gy (p 40%, vs. 54% for mLi </= 40% (p 85% vs. 60% for CR </= 84% (NS). For patients treated according to our protocol, i.e., 24-26 Gy on the 60%-70% isodoses, OR was higher (68%) than for other patients (47%) (p = 0.02). After multivariate analysis, absence of previous embolization and mono isocentric-irradiation were independent factors predicting obliteration. Complications were: recurrent hemorrhage, 4 patients (1 patient died); brain necrosis on MRI, 2 patients; subsequent epilepsy, 4 patients; other subsequent neurologic deficits, 3 patients. CONCLUSION Overall OR was 64% (48-96 months follow-up). After monovariate analysis higher ORs were associated with smaller volumes </= 4200 mm(3), smaller nidus size </= 25 mm, absence of prior embolization, monoisocentric RS, higher values for mean and minimum lesion doses and compliance to our protocol. Higher values for the peripheral dose and isodose tended to give better results. Multivariate analysis showed that the absence of prior embolization and monoisocentric irradiation were independent factors predicting successful irradiation.

Salvage irradiation of oropharyngeal cancers using iridium 192 wire implants: 5-Year results of 70 cases

Between May 1971 and November 1980, 70 patients with recurrent or new oropharyngeal cancers arising in previously irradiated tissues were treated using iridium 192 afterloading techniques. The actuarial local control was 72% at 2 years and 69% at 5 years. Although local control of the tumor was achieved in the majority of these patients, only 10 patients remained alive at 5 years (14%). Patients with lesions of the faucial arch and posterior pharyngeal wall had the best results; local control was achieved in 100% of these patients. Patients with lesions of the base of tongue and of the glosso-tonsillar sulcus had poorer results; local control was achieved in 61%. Because these results compare favorably with the results of previously published series, we recommend re-irradiation with brachytherapy for recurrent or new malignancies arising in a previously irradiated oropharynx. When the lesion is located in the faucial arch, brachytherapy is the treatment of choice. When the lesion is located in the base of tongue, brachytherapy is a reasonable option.

Results of definitive irradiation in a series of 305 epidermoid carcinomas of the anal canal

PURPOSE To evaluate our data concerning the prognostic factors for locoregional control, survival, late complications, and sphincter conservation in a series of epidermoid cancers of the anal canal without clinical evidence of metastasis. METHODS AND MATERIALS Between June 1972 and January 1997, 305 patients were treated with curative-intent radiotherapy (RT). The T stage according to the 1987 International Union Against Cancer classification was T1 in 26, T2 in 141, T3 in 104, and T4 in 34. Forty-nine patients had nodal involvement at presentation. The pretreatment anal function score, according to our in-house system, was 0 for 22 patients, 1 for 182, 2 for 74, 3 for 7, and 4 for 11 patients; for 9 patients, scores were unavailable. The treatment started with external beam radiotherapy (EBRT) in 303 patients (median dose 45 Gy). After a rest period of 4-6 weeks, a boost of 20 Gy was delivered by EBRT in 279 patients and by interstitial (192)Ir brachytherapy in 17 patients. Seven patients received only one course of EBRT (mean dose 49.5 Gy), and 2 patients were treated with interstitial (192)Ir brachytherapy alone (55 Gy and 60 Gy). Concomitant chemotherapy (5-fluorouracil and either mitomycin C or cisplatin) was delivered to 19 patients. The mean follow-up was 103 months (median 84). RESULTS At the end of RT, the local tumor clinical complete response rate was 96% for T1, 87% for T2, 79% for T3, and 44% for T4. Of the 61 locally progressive tumors, 27 (44%) were salvaged with abdominoperineal resection. The rate of local tumor relapse was 12%. Among 37 local tumor relapses, 20 (54%) were salvaged with abdominoperineal resection and one with interstitial (192)Ir brachytherapy. The overall local control rate (with or without salvage local therapy) was 84%. The local control rate with good anal function (score 0 or 1) was 56.5%. Of 181 available patients with their anus preserved, 94% had good anal function. For a subgroup of 15 patients with a tumor length of <2 cm and without nodal involvement, the clinical complete response rate after RT completion was 100%, the local control rate with or without local salvage treatment was 100%, and among 13 available patients with their anus preserved, the anal function score was good in 12 patients (92%). The 10-year disease-free survival rate was 74%. After multivariate analysis, three independent predictive factors significantly influenced disease-free survival: the interval between the two courses of RT (>38 days vs. < or =38 days, p = 0.0025), pretreatment anal function score (0 vs. 1 vs. 2 vs. 3 vs. 4, p = 4.4.10(-6)), and clinical complete response after RT completion (no complete response vs. complete response, p = 2.5.10(-14)). CONCLUSION We confirm the excellent results with RT in T1 and T2 lesions. However, to improve survival without colostomy with good anal sphincter function, chemoradiotherapy should be preferred for tumors > or =2 cm in length and for locally advanced tumors.

Single-fraction stereotactic radiotherapy: a dose–response analysis of arteriovenous malformation obliteration

PURPOSE Stereotactic radiotherapy delivered in a high-dose single fraction is an effective technique to obliterate intracranial arteriovenous malformations (AVM). To attempt to analyze the relationships between dose, volume, and obliteration rates, we studied a group of patients treated using single-isocenter treatment plans. METHODS AND MATERIALS From May 1986 to December 1989, 100 consecutive patients with angiographically proven AVM had stereotactic radiotherapy delivered as a high-dose single fraction using a single-isocenter technique. Distribution according to Spetzler-Martin grade was as follows: 79 grade 1-3, three grade 4, 0 grade 5, and 18 grade 6. The target volume was spheroid in 74 cases, ellipsoid in 11, and large and irregular in 15. The targeted volume of the nidus was estimated using two-dimensional stereotactic angiographic data and, calculated as an ovoid-shaped lesion, was 1900 +/- 230 mm3 (median 968 mm3; range 62-11, 250 mm3). The mean minimum target dose (Dmin) was 19 +/- 0.6 Gy (median 20 Gy; range: 3-31.5). The mean volume within the isodose which corresponded to the minimum target dose was 2500 +/- 300 mm3 (median 1200 mm3; range 75-14 900 mm3). The mean maximum dose (Dmax) was 34.5 +/- 0.5 Gy (median 35 Gy; range 15-45). The mean angiographic follow-up was 42 +/- 2.3 months (median 37.5; range 7-117). RESULTS The absolute obliteration rate was 51%. The 5-year actuarial obliteration rate was 62.5 +/- 7%. After univariate analysis, AVM obliteration was influenced by previous surgery (p = 0.0007), Dmin by steps of 5 Gy (p = 0.005), targeted volume of the nidus (< or = 968 mm3 vs. >968 mm3; p = 0.015), and grade according to Spetzler-Martin (grade 1-3 vs. grade 4-6; p = 0.011). After multivariate analysis, the independent factors influencing AVM obliteration were the Dmin [relative risk (RR) 1.9; 95% confidence interval (CI) 1.4-2.5; p < 0.0001] and grade distribution according to Spetzler-Martin (RR 1.4; 95% CI 1.1-1.7; p = 0.010). Delayed complications were observed in eight patients. The 5-year actuarial rate of delayed complications was 7.4%. CONCLUSION After stereotactic radiotherapy delivered in a single high dose using a single-isocenter technique, the success rate for complete obliteration is independently correlated to Dmin but does not seem to be influenced by Dmax and the targeted volume of the nidus.

Primary chemotherapy and preoperative irradiation for patients with stage II larger than 3 cm or locally advanced non-inflammatory breast cancer☆

BACKGROUND AND PURPOSE To evaluate possibility of breast-conserving therapy and outcome for patients with locally advanced non-inflammatory breast cancer (LABC) and stage II >3 cm in diameter after primary chemotherapy (CT) followed by external preoperative irradiation (RT). MATERIALS AND METHODS Between 1982 and 1990, 147 patients were treated by four courses of induction CT (doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil) followed by preoperative RT (45 Gy to the breast and nodal areas) and a fifth course of CT. Three different loco-regional approaches were proposed depending on tumour characteristics and tumour response. After completion of local therapy, all patients received a sixth course of CT and a maintenance adjuvant CT regimen without anthracycline. RESULTS Mastectomy and axillary dissection were performed in 52 patients, and conservative treatment in 95 patients (48 achieved complete remission and received additional radiation boost to initial tumour bed; 47 had a 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 loco-regional failure rate was 20% after RT alone, 23% after wide excision and RT and 6% after mastectomy (P = 0.85). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumour size. Ten-year overall survival rate was 66%; it was not influenced by local treatment (conservative vs. non-conservative local treatment, P = 0.89). However, local failure significantly decreased overall survival (P < 0.0001). After multivariate analysis, tumour response after induction CT and clinical stage had a significant impact on survival. CONCLUSIONS The present data indicate that induction CT followed by preoperative RT may permit the selection of some patients with LABC or stage II >3 cm for conservative treatment. The impact of this treatment modality on long term survival remains to be established.

Definitive radiation treatment for early stage carcinoma of the soft palate and uvula: the indications for iridium 192 implantation.

From 1971 to 1984 59 T1 and T2 carcinomas of the soft palate and uvula were treated definitively by irradiation at the Henri Mondor hospital. Included are ten patients previously irradiated to the oropharyngeal area for either a carcinoma of the soft palate or another malignancy. Sixteen patients were treated by external irradiation alone, 14 by Iridium 192 implantation, and 29 by a combination of the two. Two techniques of implantation were used: the guide gutter technique (33 patients) and the plastic tube technique (10 patients). Clinically negative neck nodes (51/59) either received prophylactic telecobalt therapy (39/51) or were surveilled (12/51). Clinically involved nodes (8/59) were managed either by external irradiation alone (4/8) or combined with neck dissection (4/8). Local failure was 25% (4/16) after exclusive telecobalt therapy, 18% (5/19) after combined telecobalt therapy and implantation, and 0% (0/14) after Iridium 192 implantation alone. No local failures were seen with the plastic tube technique (0/10) as compared to 15% (5/33) for guide gutters. Only two nodal failures were observed (2/59: 3%). Crude 5-year disease-free survival was 33%. Severe complications were limited to one osteonecrosis, one soft tissue necrosis, and one partial palatal incompetence. Salivary impairment was reduced when implantation was used for part or all of the treatment. We recommend 45 Gy external radiation followed by 30 Gy from Iridium 192 implantation using the plastic tube method unless there has been prior oropharyngeal irradiation, in which case we give 60 Gy from implantation alone. For clinically negative neck nodes, we recommend 45 Gy prophylactic external neck irradiation. For clinically positive lymph nodes, this should be followed by either a 25 to 30 Gy boost to the involved nodes or a neck dissection.

Interstitial radiation therapy for squamous cell carcinoma of the tonsillar region: The creteil experience (1971–1981)

From July 1971 to December 1981, 33 selected patients with T1, T2 tumors of the tonsillar region were treated according to the following protocol: 1. Telecobalt therapy to the primary site and to neck nodes to a dose of 45 Gy. 2. Brachytherapy to the primary site to a dose of 30 Gy using iridium 192. 3. Boost dose to involved neck nodes with electrons, or radical neck dissection, whether N1, N2, or N3. The actuarial disease-free survival was 76% when all patient groups were included and 80% for the N0 patients. The local control rate was 100%. Disease control in the neck was 94% overall and 100% for the N0 group. These results favor the use of this protocol for superficial, minimally infiltrating tumors less than 4 cm in diameter, without obvious extension to the base of the tongue or retromolar trigone.