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.

A retrospective study of three treatment techniques for T1-T2 base of tongue lesions: surgery plus postoperative radiation, external radiation plus interstitial implantation and external radiation alone.

One hundred and ten patients with base of tongue tumors less than or equal to 4 cm in diameter (T1 and T2 by the UICC staging system) were treated according to three different methods; surgery followed by external radiation in 27 cases, external radiation followed by interstitial implantation in 29 cases, and external radiation alone in 54 cases. The median follow-up is 8 years with a minimum of 4 years. Local failure occurred twice as often in patients treated by external radiation alone (43%) compared to the other two therapeutic modalities (20.5% for external radiation plus implantation and 18.5% for surgery plus radiation). Ninety per cent of recurrences occurred within the first 2 years. The 5-year survival rate for N0 and N1 nodal disease is 30.5% for patients treated by external radiation alone and 50% for the other two methods. This survival difference is related to poorer local control. Surgery plus external radiation gives identical results to those of external radiation and interstitial implantation, but surgery is only practical for peripheral base of tongue tumors and it has poorer functional results. External radiation followed by interstitial implantation is, in our opinion, the best of the three therapeutic techniques for T1 and T2 base of tongue tumors.

Positive clinical experience with misonidazole in brachytherapy and external radiotherapy.

We performed a clinical evaluation of Misonidazole (MISO) radiosensitization in brachytherapy and two schedules of hypofractionated external radiotherapy in 3 non randomized studies. MISO (1 g/m2/d) was administered to patients with ENT tumors treated by brachytherapy, two applications of 35 Gy each with an interval of 1 month. For 46 patients with tumor responses less than 50% (in the largest dimension) at time of second application, 21 received MISO and 25 did not. For these poorly radiosensitive tumors, the addition of MISO significantly increased the rate of complete remission from 9/25 (36%) in controls to 14/21 (67%) (p less than 0.05). We studied MISO with radiation hypofractionation for conservative breast cancer with 4 fractions over 17 days (5 Gy on days 1, 3 and 6.5 Gy on days 15 and 17). Brachytherapy alone was delivered three weeks later. MISO (1 g/m2/d) was given to 38 patients with 87 acting as controls. Radiosensitization was measured by mean tumor diameter at brachytherapy, which showed a residual mass of 33% in the group without MISO and only 17% in the group with MISO (p less than 0.05). We also studied MISO with radiation hypofractionation for large ENT tumors with 14 fractions over 45 days, 2 sessions with a 4 hour interval per day for totals of 6 Gy on days 1 and 3; 8 Gy on days 15, 17, 29, 31; and 6 Gy on day 45. MISO (1 g/m2/d) was given to 49 patients with 21 acting as controls. MISO increased the rate of complete remission from 7/21 (33%) in controls to 32/49 (65%) (p less than 0.02).

Iridium 192 plesiocurietherapy using silicone elastomer plates for extensive locally recurrent breast cancer following chest wall irradiation.

From July 1985 to October 1988, 11 patients with prior treatment for breast cancer, and presenting an isolated superficial widespread inoperable chest wall recurrence, underwent plesiocurietherapy for salvage. Most patients (91%) had had a mastectomy. The recurrences developed in tissue that had previously been irradiated to 45-55 Gy in three patients and 65 Gy in eight patients. Salvage was attempted using two or three courses of plesiocurietherapy at monthly intervals to decrease treatment complications. The position of the active sources was maintained parallel but slightly shifted at each application. A total dose of 60 Gy was delivered to a Reference Isodose (R.I.) located 2 to 4 mm under the skin surface. The guide system consisted of plastic tubes inserted at 1.5 cm intervals into flexible silicone plates that were applied to the skin surface to maintain the actives lines 0.5 cm above the skin surface. The high dose sleeves surrounding the actives lines (dose greater than 2 x R.I.) were contained within the thickness of the silicone plate. The mean surface treated was 480 cm2 (range 30-1030 cm2). Two patients had continued progression of the lesions within the treated volume during and after curietherapy and died rapidly of metastatic disease. Nine (89%) patients showed complete regression of treated lesions. But two patients developed a new recurrence outside the treated volume. Complications were acceptable: five patients experienced regressive moderate to severe radiation dermatitis and one had skin necrosis that healed in 2 months. These preliminary results have shown that even when tumor extension and previous treatment theorically counter-indicate further local therapy for locally recurrent breast cancer, it is possible to obtain immediate and, at times, lasting control of local disease using two or three courses of plesiocurietherapy with a source shift.

The use of a specific hypofractionated radiation therapy regimen versus classical fractionation in the treatment of breast cancer: a randomized study of 230 patients.

An ongoing randomized study of a specific regimen of hypofractionated radiation therapy (IHF) versus classical or standard radiation therapy (IC) for breast cancer was begun in the Department of Radiation Therapy of the Necker Hospital, Paris France, in January 1982. Breast cancer patients entered into this study received either IC to deliver 45 Gy in 25 fractions over 33 days or a specific IHF regimen to deliver 23 Gy in 4 fractions over 17 days. As of June 1989, 525 patients had been entered into the study. The first 230 patients treated from 1982 through December 1984 had a minimum follow-up of 4 years (range: 4 to 7 years). Preliminary analysis of the results in these first 230 patients are presented. The distribution of patients in this initial group according to clinical staging, associated treatments, and pathological nodes is as follows: T1 = 22%, T2 = 61%, T3 + T4 = 17%, palpable nodes = 28%, inflammatory signs = 7%, surgical treatment = 79% (mastectomy = 35%, tumorectomy + Ir.192 = 44%), radiation alone + neoadjuvant chemotherapy = 21%, N+ = 50% of patients undergoing surgery. Loco-regional recurrences developed in 7% (9/125) of patients in the IHF group and in 5% (5/105) of patients in the IC group. Complications were minor. The addition of the percentage of each complication noted results in a total of 23% for the IHF group and 19% for the IC group (one patient could present several complications). As we had previously observed when comparing these two fractionation regimens in other studies with other tumors, these preliminary results showed no evident difference in the effectiveness and rate of complications whether IHF or IC was used to treat patients with breast cancer.

Radiation-induced cognitive dysfunction: an experimental model in the old rat.

PURPOSE: To develop a model of radiation-induced behavioral dysfunction. METHODS AND MATERIALS: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. RESULTS: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p < or = 0.001) and two-way avoidance (18% vs. 40%, p < or = 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p < or = 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. CONCLUSION: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes.

Split course interstitial brachytherapy with a source shift: the results of a new iridium implant technique versus single course implants for salvage irradiation of base of tongue cancers in 55 patients.

Between January 1973 and December 1984, 55 patients with prior irradiation of the oropharynx underwent salvage irradiation for recurrent (26 patients) or second cancers (29 patients) of the base of tongue. The initial irradiation had delivered from 45 to 80 Gy to the base of tongue. One of two techniques of Iridium implantation was used for salvage. Single course implants, delivering 60 Gy, were used until June 1981 in a total of 31 patients. After June 1981, split course implants with a source shift were used in 24 patients in the hope of decreasing treatment complications. The first and second course of the split course implants delivered 35 and 30 Gy, respectively, at a 1-month interval. The active lines of the second implant were placed parallel to and between the position of the lines of the first implant. This shift in the source position resulted in a more uniform dose within the treated volume with a 60% reduction in the high dose sleeves. The overall 3-year survival was 19% (28% T less than or equal to 3 cm). The overall local failure rate was 45.5% (25/55). The difference between the local failure rate after single course implants (52%) and after split course implants (37.5%) was not statistically significative. The response observed after the first course of a split course implant proved to be a reliable indication of the probability of achieving local control after a full course of treatment: 2/14 failures (14%) if the response was greater than or equal to 75% versus 7/10 (70%) if the response was less than 75% (p less than 0.01). The only complication noted in the 40 patients achieving immediate local control after either implant technique was mucosal necrosis. The introduction of split course implants was followed by a two and a half fold decrease in the incidence of necrosis: 43% (9/21) in the single course group and 16% (3/19) in the split course group (p = 0.05). Interstitial brachytherapy offers an effective and reasonable option for salvage therapy in patients with recurrent and second cancers occurring in the base of tongue even when the tumor arises in a zone that has previously received high dose irradiation. The use of split course implants with a shift in the position of the active lines at the time of the second implant significantly decreases the risk of radionecrosis.

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.

Split course interstitial brachytherapy with a source shift: the results of a new technique for salvage irradiation in recurrent inoperable cervical lymphadenopathy greater than or equal to 4 cm diameter in 23 patients.

Between June 1981 and December 1986, 23 patients with prior irradiation of the neck for epithelial ENT tumors underwent salvage irradiation for isolated recurrent inoperable cervical lymphadenopathy greater than or equal to 4 cm. The initial irradiation had delivered 45-80 Gy to the cervical lymph nodes. Split course interstitial brachytherapy was used with a source shift in an attempt to decrease treatment complications. The first and second course of the split course implants delivered 35 Gy and 30 Gy at a 1 month interval. The active lines of the second implant were placed parallel to and in between the position of the lines of the first implant. Three patients did not receive the second implant (one death, one disease evolution, one necrosis). For the patient who died between the first and second implants the local control rate could not be determined. The immediate overall local control rate was 73% (16/22) with a later recurrence rate of 62% (10/16), but only in three cases was recurrence within the treated volume (19%-3/16). The local control rate was better (3/9) if the initial lymphadenopathy was greater than or equal to 4 cm less than or equal to 6 cm but worse (3/13) in those with initial lymphadenopathy greater than 6 cm. Survival of these patients overall was poor with 26% survival at 1 year and 13% at 2 years. Tolerance overall was acceptable with tissue necrosis occurring in 36.5% of cases including those with initial skin involvement. If these cases were excluded the necrosis rate was only 15.5%. In this patient population with inoperable recurrent cervical lymphadenopathy in whom a further dose of external irradiation is not possible interstitial brachytherapy should be considered. Our technique of implantation, split over two sessions with a source shift, is practicable with an acceptable toxicity. It may be used even after high dose external beam irradiation and in large volumes of disease, and it gives better results than classical brachytherapy.

Interstitial iridium-192 for bladder cancer (a multicentric survey: 205 patients).

Interstitial irradiation is a technique currently used in the treatment of bladder cancer. We report the data on 205 patients (177 men and 28 women) treated in eight French centers. The patients had received the following treatment: a short course of pre-operative pelvic irradiation, followed by surgery consisting of partial cystectomy or tumor resection, and implantation of plastic tubes filled with inactive lead wires, which were replaced by iridium 192 wires. The tumor characteristics were: transitional cell carcinoma, 88.8%; mean size of the tumor, 29 mm; pathological stages: pTis, 1; pT1, 98; pT2, 66; pT3a, 26; pT3b, 9; pT4, 1; unknown, 4 respectively; surgical lymph node status: N+, 3; N-, 118; no node dissection, 84. The mean follow-up was 51 months. Intravesical failures were seen in 35 patients (17.0%), 25 (71.4%) of them without metastases or regional recurrences. Twenty-one patients (10.2%) presented distant metastases, 2/3 of them suffered no bladder relapse. The 5-year survival, calculated according to the Kaplan-Meier method (all causes of death taken together) was 77.4% for the T1, 62.9% for the T2, and 46.8% for the T3. Fifty-three patients had immediate side-effects and three died from surgical complications. Twenty-nine patients had delayed bladder side-effects (haematuria, fistula, chronic cystitis). Six patients presented an ureteral stenosis. Of the disease-free survivors, 96.1% retained the bladder function. Three factors were significantly predictive of delayed side-effects: partial cystectomy, pre-operative radiotherapy total dose, and linear activity of the wires (p < 0.01). Comparing our results to different authors' series interstitial irradiation is likely to provide a high local and general control of the disease and good quality of life in patients with selected tumors.

An experimental model of acute encephalopathy after total body irradiation in the rat: effect of liposome-entrapped Cu/Zn superoxide dismutase.

PURPOSE: To develop an experimental model of acute encephalopathy following total body irradiation in rats and to define the therapeutic effect of liposome-entrapped Cu/Zn superoxide dismutase. METHODS AND MATERIALS: A total of 120 4-month-old rats received 4.5 Gy total body irradiation (TBI) while 120 rats received sham irradiation. A behavioral study based on a conditioning test of negative reinforcement, the one-way avoidance test, was performed 5 hours before irradiation and repeated the following days. Subcutaneous treatment was started 1 hour after irradiation and repeated daily for 2 weeks. In both the irradiated and sham group, three subgroups were defined according to the treatment received: liposome-entrapped Cu/Zn superoxide dismutase (0.5 mg/kg), liposomes only, normal saline. RESULTS: This work comprised two consecutive studies. In study A (90 rats) the one-way avoidance test was administered daily from day 0 to day 4 with a recall session at day 14. In study B (validation phase in 150 rats) the behavioral test was performed only from day 0 to day 6. Before irradiation, all rats showed a similar behavioral response. Study A (6 groups of 15 rats): Following TBI, irradiated rats treated with liposomes only or saline demonstrated a significant delay in learning the one-way avoidance test in comparison with sham-irradiated rats (0.05 < p <0.001 depending upon the day of evaluation and the subgroup type). In contrast, irradiated rats treated with liposome-entrapped Cu/Zn superoxide dismutase did not differ from sham-irradiated rats. Study B (6 groups of 25 rats): The results were the same as those in study A, demonstrating a significant delay in the learning of the test in the liposome and saline-treated irradiated rats in comparison with sham-irradiated rats (0.02 < p < 0.001). The irradiated rats, treated with liposome-entrapped Cu/Zn superoxide dismutase did not differ from the sham-irradiated controls. CONCLUSION: This study indicates that a relatively low dose of total body irradiation induces a substantial acute learning dysfunction in the rat. This effect is prevented by the administration of liposome-entrapped Cu/Zn superoxide dismutase.

Successful treatment of radiation-induced fibrosis using Cu/Zn-SOD and Mn-SOD: an experimental study.

PURPOSE: To establish how far liposomal copper/zinc superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD), respectively, reduce radiation-induced fibrosis (RIF), using a well-characterized pig model of RIF permitting the design of a controlled laboratory experiment. METHODS AND MATERIALS: In this model of acute localized gamma irradiation simulating accidental overexposure in humans, three groups of five large white pigs were irradiated using a collimated 192Ir source to deliver a single dose of 160 Gy onto the skin surface (100%) of the outer side of the thigh. A well-defined block of subcutaneous fibrosis involving skin and skeletal muscle developed 6 months after irradiation. One experimental group of five pigs was then injected i.m. with 10 mg/10 kg b.wt. of Cu/Zn-SOD, twice a week for 3 weeks, and another experimental group of five was injected with 10 mg/10 kg b.wt. of Mn-SOD, three times a week for 3 weeks. Five irradiated control pigs were injected with physiological serum. Animals were assessed for changes in the density of the palpated fibrotic block and in the dimensions of the projected cutaneous surface. Block depth was determined by ultrasound. Physical and sonographic findings were confirmed by autopsy 12-14 weeks after completing SOD injections. The density, length, width, and depth of the fibrotic block, and the areas and volume of its projected cutaneous surface were compared before treatment, 1, 3, and 6 weeks thereafter, and at autopsy, 12-14 weeks after treatment ended. RESULTS: The experimental animals exhibited no change in behavior and no abnormal clinical or anatomic signs. Whether they were given Cu/Zn- or Mn-SOD, significant and roughly equivalent softening and shrinking of the fibrotic block were noted in all treated animals between the first week after treatment ended and autopsy, when mean regression was 45% for length and width, 30% for depth, and 70% for area and volume. Histologic examination showed completely normal muscle and subcutaneous tissue surrounding the residual scar. This replacement of scar tissue by normal tissue in experimental animals and the 50% decrease in the linear dimensions of the scar were comparable to the results obtained in previous clinical studies and highly significant compared to the clinical and autopsy results for the control animals. CONCLUSIONS: Our results are striking and comparable to the results obtained in our previous clinical study after liposomal Cu/Zn-SOD treatment. To our knowledge, this is the first time that two agents have been shown to reverse the radiation-induced fibrotic process in experimental animals and to permit the regeneration of normal tissue in a zone of well-established postirradiation fibrosis.

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)

Pulsed dose rate brachytherapy in head and neck cancers. Feasibility study of a French cooperative group.

PURPOSE: To prospectively evaluate the feasibility of pulsed dose rate (PDR) brachytherapy to mimic the continuous low dose rate (cLDR) iridium wire technique in head and neck carcinomas. MATERIALS AND METHODS: A series of 30 patients were included from June 1995 to May 1998. The primaries were located in the oral cavity (four T1, seven T2 and two T3), the velotonsillar arch (eight T1 and eight T2) and the posterior wall (one T3). Thirteen were irradiated by exclusive brachytherapy (dose, > or =45 Gy). The PDR delivered 0.5 Gy/pulse, one pulse/h, day and night, to mimic cLDR irradiation. RESULTS: The implantation was feasible for all the patients, usually easy and of good quality. The mean duration/pulse was 13 min, with a mean source activity of 171 mCi. Patient tolerance was poor in nine cases. Sixteen patients could receive the whole PDR treatment with a total ranging from 30 to 120 pulses without any problem. Seven had short breakdowns (< or =6 h). Seven had definitive breakdowns, but could end the irradiation by manual afterloading of iridium 192 wires. The radioprotection was better (or complete), except for one patient. Most of the breakdowns were related to kinking or flattering of the tube. CONCLUSIONS: PDR is feasible in head and neck carcinomas, but necessitates improvement of the quality and control of the plastic tubes.

Radiosurgery for re-irradiation of brain metastasis: results in 54 patients.

PURPOSE: To evaluate in terms of probabilities of local-regional control and survival, as well as of treatment-related toxicity, results of radiosurgery for brain metastasis arising in previously irradiated territory. PATIENTS AND METHODS: Between January 1994 and March 2000, 54 consecutive patients presenting with 97 metastases relapsing after whole brain radiotherapy (WBRT) were treated with stereotactic radiotherapy. Median interval between the end of WBRT and radiosurgery was 9 months (range 2-70). Median age was 53 years (24-80), and median Karnofski performance status (KPS) 70 (60-100). Forty-seven patients had one radiosurgery, five had two and two had three. Median metastasis diameter and volume were 21 mm (6-59) and 1.2 cc (0.1-95.2), respectively. A Leksell stereotactic head frame (Leksell Model G, Elektra, Instrument, Tucker, GA) was applied under local anesthesia. Irradiation was delivered by a gantry mounted linear accelerator (linacs) (Saturne, General Electric). Median minimal dose delivered to the gross disease was 16.2 Gy (11.8-23), and median maximal dose 21.2 Gy (14- 42). RESULTS: Median follow-up was 9 months (1-57). Five metastases recurred. One- and 2-year metastasis local control rates were 91.3 and 84% and 1- and 2-year brain control rates were 65 and 57%, respectively. Six patients died of brain metastasis evolution, and three of leptomeningeal carcinomatosis. One- and 2-year overall survival rates were 31 and 28%, respectively. According to univariate analysis, KPS, RPA class, SIR score and interval between WBRT and radiosurgery were prognostic factors of overall survival and brain free-disease survival. According to multivariate analysis, RPA was an independent factor of overall survival and brain free-disease survival, and the interval between WBRT and radiosurgery longer than 14 months was associated with longer brain free-disease survival. Side effects were minimal, with only two cases of headaches and two of grade 2 alopecia. CONCLUSION: Salvage radiosurgery of metastasis recurring after whole brain irradiation is an effective and accurate treatment which could be proposed to patients with a KPS>70 and a primary tumour controlled or indolent. We recommend that a dose not exceeding 14 Gy should be delivered to an isodose representing 70% of the maximal dose since local control observed rate was similar to that previously published in literature with upper dose and side effects were minimal.

Post-radiation severe xerostomia relieved by pilocarpine: a prospective French cooperative study.

BACKGROUND AND PURPOSE: The aim of the study was: (1) to confirm the action of pilocarpine hydrochloride (Salagen) against xerostomia: (2) to correlate the response to dose/volume radiotherapy parameters. MATERIALS AND METHODS: From June 1995 to February 1996, 156 patients with severe radiation induced xerostomia received pilocarpine hydrochloride orally. IS mg per day with a 5 mg optional increase at S weeks up to a daily dose of 25 mg beyond 9 weeks. RESULTS: One hundred and forty five patients are fully evaluable. Treatment compliance was 75%. Thirty eight patients (26%) stopped treatment before week 12 for acute intolerance (sweating, nausea, vomiting) or no response. No severe complication occurred. Ninety ses en patients (67%) reported a significant relief of symptoms of xerostomia at 12 weeks. Within 12 weeks, the size of the subgroup ith normal food intake almost doubled (13-24 patients) while the size of the subgroup with (nearly) impossible solid food ingestion decreased by 38% (47 vs. 29 patients). The impact on quality of life was considered important or very important by 77% of the responders. CONCLUSIONS: No difference was found according to dose/volume radiotherapy parameters suggesting that oral pilocarpine hydrochloride: (1) acts primarily by stimulating minor salivary glands: (2) can be of benefit to patients suffering of severe xerostomia regardless of radiotherapy dose/volume parameters: (3) all responders are identified at 12 weeks.

Endocurietherapy of penis cancer.

Forty-five carcinomas of the penis have been treated with curietherapy using 192Ir to a dose of 6500 rad. With a minimum follow-up of 4 years, it appears that small lesions (less than 30 mm) have excellent local results (2 recurrences in 14 cases). With only a slight potential for lympatic extension, these patients are alive without evidence of disease after 4 years. The lesions of moderate size (30-40 mm) have a poorer prognosis because of more frequent lymphatic extention and disseminated metastases; in contrast, the local results are still quite satisfactory (4 recurrences in 24 cases). The large lesions (more than 40 mm) recur or necrotize (5 recurrences and 2 necroses in 7 cases). In conclusion, curietherapy of epidermoid carcinomas of the penis is an excellent primary treatment for small or moderate lesions (T1, T2, and T3a) if one wishes to avoid surgical mutilation.

Postoperative radiation therapy for cervical lymph node metastases from an occult squamous cell carcinoma.

One hundred thirteen patients with cervical metastases from a squamous cell carcinoma and no evidence of the primary tumor were treated for cure by surgery and routine large-field postoperative irradiation. Patients were staged according to the 1987 American Joint Committee on Cancer (AJCC) classification. There were 24 N1, 54 N2, 29 N3, and 6 Nx lesions. One hundred four patients underwent cervical lymph node dissection and 9 had adenectomy. All patients received postoperative external beam therapy to the entire naso-oro-pharyngo-larynx and all cervical lymphatics. The overall nodal failure rate was 13.7%. Nodal failure was significantly correlated with N staging (P = .01) and with the number of histologically involved nodes (P = .05). NOdal failure was 21% when nodes were initially fixed versus 7.5% when they were not (P = .07) and 18% when there was extracapsular spread versus 4.3% when the capsule was intact (P = .11). Eleven patients (9.7%) developed a subsequent primary lesion. In 3 patients (2.6%), this primary was located in the previously irradiated area and, in 2 cases, under the anterior block of lateral fields. Metastases occurred in 18 patients (16%). The five-year overall survival rate was 38%. Survival was correlated with N staging (P less than .02), nodal fixation (P = .05), extracapsular spread (P = .01) and loosely with the number of histologically involved nodes (P = .08). On the contrary, histological differentiation did not influence the local control rate, nor the development of metastases or subsequent primary lesions. Large-field prophylactic radiation therapy appears to be effective in preventing the emergence of initially occult primary lesions. However, control of disease in the neck and survival remain disappointing in patients with advanced nodal disease, even after combined surgery and radiation therapy.

Salvage split course brachytherapy for tonsil and soft palate carcinoma: treatment techniques and results.

From December 1981 to October 1990, 28 patients with prior irradiation of the oropharynx underwent salvage brachytherapy for a squamous cell carcinoma of the tonsil and/or the soft palate. The patients were free of cervical nodes and without metastatic disease. There were 4 immediate failures of radiotherapy, 14 local recurrences, and 10 new malignancies. The mean size of the lesion was 2.7 +/- 1.7 cm (range, 0.5 to 7 cm). The initial irradiation had delivered 40 to 80 Gy (mean, 69 Gy) to the oropharynx with a mean interval between external therapy and salvage treatment of 22 +/- 28 months. Salvage brachytherapy consisted of two split course implants done 1 month apart, delivering 35 and 30 Gy, respectively. Fifteen patients (46.5%) were clinically disease-free before the second implant and 23 (82%) were clinically disease-free at the end of treatment. Five local failures have been observed without any influence of the tumor size, the topographic site of the tumor, or the histological differentiation. Of the 4 patients who previously had failed with external beam therapy, 3 were disease-free after salvage brachytherapy. Among the 23 patients in complete remission, 4 (17%) presented a local recurrence within a mean time of 5 months. The overall local control rate was 68% with a mean follow-up of 41 +/- 29 months. The overall actuarial survival was 25% and 19% at 2 and 5 years, respectively; it was 30% at 5 years for the patients presenting with lesions less than or equal to 3 cm. Tolerance was acceptable. Among the 23 patients who achieved complete remission, subsequent soft-tissue necrosis was observed in 4 cases. For these 4 patients, the interval between previous radiation therapy and salvage treatment was short (mean, 7 months). Interstitial split course brachytherapy offers an effective and reasonable option for salvage therapy in patients with recurrent and second cancers occurring in the tonsillar region and in the soft palate, even when the tumor arises in a zone that has previously received high-dose irradiation.

Use of perioperative or split-course interstitial brachytherapy techniques for salvage irradiation of isolated local recurrences after conservative management of breast cancer.

Treatment of local recurrence after conservative management for breast cancer is mastectomy. When mastectomy is contraindicated or refused, could brachytherapy be a therapeutic alternative for such isolated local relapses (ILR)? From February 1977 to June 1990, 38 patients, previously treated by radiation therapy or by a combination of radiotherapy and surgery for breast cancer, underwent salvage brachytherapy for an ILR. Fifteen patients were treated by limited tumorectomy plus 30 Gy perioperative brachytherapy for a 2.4-cm mean diameter IRL (Group A). Twenty-three patients were treated by exclusive split-course brachytherapy, delivering 60-70 Gy by two implants at 1-month interval, for a 3.9-cm mean diameter IRL (Group B). All patients achieved a clinical complete response after treatment. With a mean follow-up of 40 +/- 24 months, eight patients (21%) experienced local relapse between 9 and 48 months (four patients in Groups A and B). This second local recurrence was isolated in one case and was associated with metastatic disease in seven cases. At 5 years, overall survival was 55% (61% for Group A and and 50% for Group B). Three patients developed local complications requiring mastectomy (skin necrosis, two patients; severe breast pain, one patient). Cosmetic results in locally controlled patients were good in four patients, acceptable in twelve patients, mediocre in nine patients, and nonvaluable in two patients. Both perioperative brachytherapy and exclusive split-course brachytherapy appear to be feasible techniques and may be used occasionally as an alternative therapy to radical mastectomy for ILR.