Economic implications of hepatic arterial infusion chemotherapy in treatment of nonresectable colorectal liver metastases. Meta-Analysis Group in Cancer.

BACKGROUND: Approximately 20% of patients with colorectal cancer die of metastases confined to the liver. A meta-analysis recently performed by our group confirmed that in these patients hepatic arterial infusion of 5-fluoro-2'-deoxyuridine, compared with intravenous chemotherapy with fluoropyrimidines or supportive care (including symptom palliation when necessary), improved tumor response. PURPOSE: Because of the high cost of hepatic arterial infusion, we undertook a cost-effectiveness analysis that related the cost of such therapy to its medical efficacy. METHODS: The patient population was drawn from the seven randomized clinical trials included in the meta-analysis and included individual data on 654 patients. Of these seven trials, five compared hepatic arterial infusion and intravenous chemotherapy and two compared hepatic arterial infusion and a control group in which some patients could be left untreated. Patients assigned to receive hepatic arterial infusion made up the hepatic arterial infusion group; the other patients constituted the control group. The measures of efficacy were survival and tumor response. Health-care costs (in 1995 U.S. dollars) were computed over the duration of patient follow-up and were derived from actual costs in two centers, one at Henri Mondor Hospital (Paris, France) and the other at Stanford University Medical Center (Palo Alto, CA). The total cost of treatment included the initial procedure, chemotherapy cycles, and main complications. RESULTS: The mean gain in life expectancy in the hepatic arterial infusion group compared with the control group was 3.2 months (standard error = 1.0 month). For patients treated by hepatic arterial infusion in Paris, the hepatic arterial infusion pump, initial hospitalization, and the entire process (including follow-up and complications) cost, on average, $8400, $15172, and $29562, respectively; in Palo Alto, these costs were $4700, $13784, and $25 208, respectively. For patients in the control groups in Paris and Palo Alto, the total treatment costs were, on average, $9926 and $5928. The additional costs of hepatic arterial infusion over control treatment were $19636 in Paris and $19280 in Palo Alto. The cost-effectiveness (i.e., the additional cost divided by the additional benefit) with respect to survival of the patients in the hepatic arterial infusion group compared with the patients in the control group was $73635 per life-year in Paris and $72300 per life-year in Palo Alto. CONCLUSIONS AND IMPLICATIONS: The cost-effectiveness of localized chemotherapy for colorectal liver metastases is within the range of accepted treatments for serious medical conditions, although it might be considered borderline by policy-makers in some countries. Prospective clinical trials should be conducted to more definitively answer this question.

Management of breast cancer in the elderly.

The management of breast cancer in elderly women was analysed by a retrospective study of 150 women over 70 years old referred to our department between 1984 and 1988. 80 were T1-T2, 33 were T3 and 34 were T4. 107 were N0 and 43 were N1-N2. 16 women (11%) were in poor health, preventing conventional treatment. Treatment choice varied with age: 60% of the women aged 70-79 (group 1) and 23% of the oldest women (group 2) were treated conventionally. The use of surgery decreased with age and surgical procedures were conventional in only 85% of the group 1 women and in 56% of the group 2 women. Definitive radiation therapy was used more frequently in the oldest women, as was primary hormone therapy. Quality of follow-up also varied with age. Five-year survival rates were still high in both groups while relapses were frequent. Breast cancer was consequently a frequent cause of death. The increase in the proportion of elderly people with breast cancers over the next few years will require validated guidelines. Specific protocols and specific rules of management must be drawn up.

Liver complications in lymphomas treated with a combination of chemotherapy and radiotherapy: preliminary results.

From May 1978 to May 1981, a total of 20 patients (18 patients with Non Hodgkin Lymphomas + 2 patients with Stage IV Hodgkin's disease) were treated with chemotherapy and whole or upper abdominal radiotherapy. All the patients were in complete remission at the time of irradiation. Shielding of the kidneys was effected at the start of treatment and the right lobe of the liver was shielded after a dose of 20 Gy was delivered. As of January 1982, 17 of the patients were alive and free of disease with a follow-up ranging from 6 to 32 months (mean follow-up of 18.5 months). Two patients were dead from their disease. Alterations in liver chemistry were observed in 5 patients, clinical jaundice or transient hepatomegaly along with changes in liver chemistry in 4 patients, classical veno-occlusive disease in 2 patients and 7 of the patients did not develop any complication. No death from complications were observed. The contribution of the following factors such as radiotherapy dose to the liver, drugs, nutritional status and associated medical conditions, towards the development of complications have been analyzed in detail.

Radiotherapy in the management of cutaneous epidemic Kaposi's sarcoma.

Between June 1986 and December 1988, we treated 149 patients who had AIDS-related epidemic Kaposi's sarcoma with cutaneous irradiation. According to Mitsayasu's staging, 34 patients (23%) had Stage I disease, 82 (55%) Stage II, 0 Stage III, and 33 (22%) Stage IV. Fifty-eight patients (39%) had previously presented with one or more opportunistic infections. Ninety-four patients (63%) had received previous treatment of their Kaposi's sarcoma: 85 (57%) with interferon and 43 (29%) with vinblastine. Among the 149 patients, we treated 88 (59%) with extended cutaneous irradiation using 4- and/or 8-MeV electron beam energy and 61 patients (41%) with localized irradiation using 45-kVp x-ray energy. The total prescribed dose was 30 Gy: 20 Gy in 2 weeks (2.5 Gy/fraction, 4 times/week), followed by 2 weeks of no irradiation, and then 10 Gy in one week by the same dose schedule. Twenty patients (13%) with edema of the lower limbs were treated using 4-Mv photon therapy with bolus. Of the 131 evaluable patients, 63% achieved a complete remission (CR) and 30% a partial remission (PR) after a mean period of 1.5 months (range: 0.5-3 months). The clinical disease stage, anatomic site, and irradiation technique did not significantly influence the remission rates, although we noticed a higher CR rate when localized irradiation was used (71% vs 55.5% for localized and extended irradiation, respectively; p = 0.08). The overall tolerance was acceptable. Complications were severe epidermitis with skin ulcerations (8% of patients), exudative epidermitis (26%), dry epidermitis (60%), and varying degrees of erythema (6%). Of the 87 patients whose AIDS remained relatively clinically stable during the observation period, recurrences occurred in 56 (64%) after an average of 5.5 months (range: 1.5-12 months). We conclude that radiotherapy is useful and can be recommended as a palliative treatment to relieve pain and physical discomfort or to achieve cosmetic improvements for patients with epidemic Kaposi's sarcoma. We also conclude that radiotherapy is most beneficial in the early stages of disease, when localized treatment is practical.

Update on low dose rate irradiation for cancers of the oropharynx--May 1986.

At the conclusion of our recently published article in this Journal on low dose rate irradiation in moderately extensive cancers of the oropharynx, we updated our results in May 1986. Here we report on an expanded group of 65 patients with a 2 year minimum follow-up; 32 patients were treated by low dose rate irradiation and 33 by conventional fractionation. Forty-four percent (14/32) low dose irradiation patients survived with NED vs 8/33 (24%) conventional fractionation patients. The highly significant differences in the level of local recurrences between patients treated by low dose rate irradiation, 5/32 (16%), compared with conventional fractionation, 20/33 (61%), highlights the enhanced efficacy of the low dose rate irradiation technique in the local cure of cancers of the oropharynx. This superior local control however is achieved at the cost of a number of necrosis, 5/32 (16%).

Management of epistaxis in Rendu-Osler disease: is brachytherapy effective?

PURPOSE: This paper reviews the results of intranasal brachytherapy for epistaxis in 43 patients with Rendu-Osler disease treated between 1971-1991 at Henri Mondor Hospital. METHODS AND MATERIALS: 2-3 intranasal catheters were afterloaded with 192Ir sources. Computer dosimetry was performed and then the dose was prescribed to an isodose thought to cover the nasal mucosa. The dose rate ranged from 0.16 Gy/h-0.63 Gy/h with a median of 0.34 Gy/h. Dose at one application ranged from 15-35 Gy with a median of 30 Gy. The severity of epistaxis was graded 1 to 5. RESULTS: The time to recurrence of significant epistaxis ranged from 6-178 months with a median of 24 months. The dose prescribed did not correlate with control rate. The only brachytherapy complication was septal perforation in 4 patients; in one this was a result of repeated nasal coagulation. CONCLUSION: We suggest that intranasal brachytherapy is a useful modality in the management of epistaxis in Rendu-Osler disease.

The indications for total cutaneous electron beam radiation therapy of mycosis fungoides.

From 1977 to 1984, we treated 34 patients with mycosis fungoides and 9 patients with B cutaneous lymphomas. Eighteen patients with mycosis fungoides were treated with total skin electron irradiation (TSEI) and had a minimum follow-up of 15 months (range 15 months to 7 years). The lowest electron energy of the linear accelerator was 8 MeV therefore we placed a plexiglas screen between the patient and the machine; the resulting electron energy was 4 MeV. The total dose was 30 Gy delivered in 12 fractions over 40 days. There were 8 males and 10 females. The median age was 48 years (ranging from 13 to 78 years). All patients were staged as follows: Stage A = superficial lesions covering less than 50% of the body surface; Stage B = superficial lesions covering more than 50% of the body surface; Stage C = tumors involving the skin, lymph nodes and/or visceral organs. Five patients with Stage A (5/5) and 5 patients with Stage B (5/5) had a complete remission, 1 stage A patient relapsed 6 months after completion of treatment. All the Stage B patients recurred between 3 and 15 months. The recurrences were localized to the skin and were well controlled with topical nitrogen mustard or puvatherapy. Among the Stage C patients, 3 did not respond to treatment and died of their disease; the remaining 5 patients achieved complete remission but they all relapsed from 2 to 9 months following completion of treatment. The median follow-up was 32 months and the average time for relapse was 6.5 months. All relapses except one (15 months) occurred within the first year. We feel that total skin electron irradiation is indicated in Stage A and B patients. However, we feel Stage C patients should receive TSEI for palliative purposes only.

Radiotherapy in the management of epidemic Kaposi's sarcoma.

PURPOSE: This study is presented to help define the role of radiotherapy in the management of epidemic Kaposi's sarcoma. METHODS AND MATERIALS: Between June 1986 and June 1993, we treated 453 patients who had acquired immunodeficiency syndrome related Kaposi's sarcoma. Two hundred fifty-two patients (55.6%) had received previous treatment for their Kaposi's sarcoma: 228 (55.3%) with interferon, and 116 (25.6%) with Vinblastine. Depending on both tumour size and location, patients were treated with extended cutaneous irradiation using 4 MeV electron beam energy and/or localized irradiation using 45-100 kV x-ray (cutaneous lesions), or 4 MV x-ray (oral tumours). A total of 5015 courses of radiation therapy was given. The intention of the treatment was closely linked to the anatomic sites. Multiple courses of treatment ranging from 10 to 20 Gy (2.5 Gy/fraction, 4 times/week) were used for Kaposi's sarcoma involving conjunctiva (n = 32 treatments), eyelids (n = 306), lips (n = 170), hands (n = 208), feet (n = 417), penis (n = 131), oral mucosa (n = 43), and anal region (n = 5). A second group including other cutaneous sites (face, trunk, limbs) was treated with a dose of 30 Gy (20 Gy in 2 weeks followed by 2 weeks rest and then a second series of 10 Gy in 1 week). RESULTS: For the first group, tolerance was generally good excluding oral cavity irradiation, with an effective palliation of symptoms (87.8% overall rate of objective responses); an enhanced mucosal reactions was noted in patients receiving oropharyngeal irradiation. For the second group, a complete regression rate of 85% was observed; tolerance was acceptable: complications were severe epidermitis with skin ulceration (5%), exsudative epidermitis (26%), dry epidermitis (60%), and varying degrees of erythema (9%). There was a significant correlation between risk of recurrence (overall recurrence rate of 71% after an average of 7.5 months) and occurrence of opportunistic infections: 85% of recurrences appeared concomitantly with accelerated course of acquired immunodeficiency syndrome. CONCLUSIONS: We conclude that radiotherapy is an efficient treatment for epidemic Kaposi's sarcoma (EKS): doses of 15.2 Gy for oral lesions and 20 Gy for lesions involving conjunctiva, eyelids, lips, hands, feet, penis, and anal region were sufficient to produce shrinkage of the tumour and good palliation of symptoms. For the other cutaneous sites, 30 Gy local field irradiation could be safely given with better short-term response. Prophylactic measures with antifungal treatment should be systematically associated with oropharyngeal irradiation, to improve tolerance to the treatment.

A comparison between low dose rate radiotherapy and conventionally fractionated irradiation in moderately extensive cancers of the oropharynx.

We report the comparative results for local tumor control between two groups of patients treated by radiotherapy fractionated in a conventional manner at normal high dose rate (29 patients with 2 years minimum follow-up and 24 patients with 3 years minimum follow-up) and by low dose rate radiotherapy (19 patients with 2 years minimum follow-up, 14 patients with 3 years minimum follow-up) with moderately extensive cancers of the oropharynx (T2b-T3a, 3-5 cm in diameter). At 2 and 3 years follow-up, the number of local recurrences in the patients treated with low dose rate radiotherapy is half (26 and 21%) that for those treated with conventionally fractionated radiation at normal high dose rates (52 and 54%). These results require more rigorous confirmation.

Influence of dose rate on local control of breast carcinoma treated by external beam irradiation plus iridium 192 implant.

From 1971 to 1983, 20 T1, 267 T2, and 53 T3 biopsy-proven adenocarcinomas of breast were definitively managed by radiotherapy. The breast and regional nodes received 45 Gy of 60Co irradiation in 25 fractions over 5 weeks (45 Gy/25/5 wks). Electrons were used to deliver a further 15 Gy/7/1.5 weeks to the internal mammary chain and 25 Gy/11/2.5 weeks to the lower axilla. The primary tumor was boosted by Iridium 192 implant for a further 37 Gy prescribed at 85% of the basal dose rate (Paris system). Rigid needles were secured by templates in single plane (58/398) or double plane (340/398) geometry. Results of the 340 two-plane implants have been analyzed to look for a possible influence of dose rate on local control. Follow-up for patients free of local recurrence is 4-204 months (median: 92 months). The 340 tumors were divided into three groups according to dose rate: 0.32-0.49 Gy/hr (n = 95), 0.50-0.59 Gy/hr (n = 120), and 0.60-0.90 Gy/hr (n = 125). The three groups are statistically comparable according to age, tumor size, mean 60Co dose, mean Iridium dose, overall treatment time, and follow-up. The local failure rate in the three groups is 27% (26/95), 20% (24/120), and 13% (16/125) (p less than 0.03, Chi square). At 15 years the estimated local control (Kaplan Meier) is 60%, 72%, and 84% (p less than 0.02, Logrank), respectively. This analysis indicates that there is a significant effect of dose rate on local control for carcinoma of the breast treated by combined external beam (45 Gy) plus Iridium 192 implantation (37 Gy). To maximize local control the authors recommend an implant dose rate of greater than or equal to 0.6 Gy/hr.

Influence of the fractionation of total body irradiation on complications and relapse rate for chronic myelogenous leukemia. The Groupe d'Etude des greffes de moelle osseuse (GEGMO).

One hundred eighty patients with chronic myelogenous leukemia, who received an unmanipulated marrow graft from an Human Leucocyte Antigen identical sibling donor, were reported to our group (G.E.G.M.O.) by 21 transplant teams. All were grafted after a total body irradiation-cytoxan conditioning regimen. Of these 180 patients, 126 were non-randomly assigned to single dose total body irradiation (STBI group) and, 54 to fractionated total body irradiation (FTBI group). With a median follow-up of 40 months, there is no statistically significant difference in the 5-year survival rate between the two groups (51% for the whole population). In a first step we demonstrate by multivariate analysis that total body irradiation fractionation can dramatically decrease the incidence of interstitial pneumonitis. However, a multivariate analysis of potent risk factors for relapse post-transplant strongly suggests that TBI fractionation is also linked to an increased relapse rate. So, a sparing effect of fractionation for lung tissue could be offset by a less effective leukemic stem cell kill. Those results from a retrospective, non-randomized, multi-institutional study clearly need additional clinical data, ideally from a randomized study.

Combined external irradiation and interstitial implantation for T1 and T2 epidermoid carcinomas of base of tongue: the Creteil experience (1971-1981).

Forty-eight patients with T1 or T2 epidermoid carcinomas of the base of tongue were treated at the Henri Mondor Hospital between 1971 and 1981. Forty-one patients received moderate dose 60Co external beam irradiation (mean: 48.6 Gy) to the primary tumor and regional nodes, followed by an interstitial iridium 192 implant to the primary tumor (mean: 32 Gy). This completed the treatment for the 30 node negative patients, but those with clinically positive nodes were managed by either an additional electron beam boost to the involved nodes or a neck dissection. Seven tumors were treated exclusively by implantation to the base of tongue (mean: 63 Gy). Five-year crude disease-free survival is 50% with 35% of patients dying of recurrent disease. Definitive local control for T1 lesions is 85% (11/13) and for T2 is 71% (25/35). A dose response effect was observed with local control of 79% (26/33) obtained with a combined dose greater than or equal to 75 Gy, but only 50% (4/8) for less than or equal to 70 Gy. For N0 patients definitive regional control is 97% and for N1-3 is 89%. Minor or moderate soft tissue ulceration was observed in 12 patients, including 3 cases that progressed to osteonecrosis. None required surgical intervention. No correlation exists between necrosis and tumor size or total dose.

Conservative treatment of bladder carcinoma by partial cystectomy and interstitial iridium 192.

From 1971 to 1984, 85 patients with bladder carcinoma were treated conservatively at the Henri Mondor Hospital by a combination of short course of pre-operative external pelvic irradiation, iliac node dissection, partial cystectomy, and iridium 192 implantation. There were 79 transitional cell carcinomas (G1: 12, G2: 25, G3: 36, Gx: 6) and 6 squamous cell carcinomas. By clinical stage, based on endoscopic resection, there were 43 T1, 30 T2, 5 T3, and 7 Tx. After partial cystectomy the pathologic stage distribution was: 41 pT1, 31 pT2, and 13 pT3. Crude disease-free survival at 5 years is 72% for T1 tumors and 55% for T2, but overall only 16% of patients died of bladder carcinoma. Local failures were seen in 11.5% of T1 and 0% of T2 tumors, and second bladder tumors developed at a distance from the treated site in 11.5% of T1 and 7% of T2. There is a non significant trend for intravesical recurrences (both local failures and second tumors) to occur more frequently for G1 tumors (25%) than for G2 (16%) or G3 (7%). At 5 years 95% of disease-free survivors have a functioning bladder. Regional or distant metastases occurred in 54% of patients with pT3 tumors and 10% of those with pT1 or pT2; within each stage there was no apparent influence of grade on metastatic risk. The four patients with histologically positive iliac nodes received additional post-operative external pelvic irradiation; three died of metastases and one is disease free at 10 years. No abdominal scar recurrences were seen. Late complications occurred in 6% of the population. For T1 tumors we suggest modification of the described protocol, eliminating the pre-operative irradiation and the lymph node dissection. If there is no doubt as to the pathologic stage after complete endoscopic resection, iridium 192 implantation delivering a dose of 60 Gy, without partial cystectomy, may be sufficient management. By contrast, for T2 tumors, all elements of the protocol seem important to obtain optimal results.

A new combined approach in the conservative management of rectal cancer.

Between 1980 and 1987, 25 patients with rectal cancer were treated with a combination of preoperative external irradiation of 35 Gy in 15 fractions over 3 weeks which was followed, 6 to 8 weeks later, by a tumorectomy and peroperative placement of a plastic tube loop for post-operative interstitial therapy by iridium-192. This boost dose was 20 Gy (Paris System) for submucosal lesions (seven patients) and 25 Gy for intramural (eight patients) and extramural (ten patients) lesions. With a mean follow-up of 40.5 months, there have been five local recurrences, the latest occurring 16 months post-tumorectomy. Two of these five patients are alive and disease-free 1 year post salvage abdominoperineal resection. The 20 patients with local control have preserved a full functional sphincter and 19 of them are disease-free; there were few complications. This sphincter preserving combined approach seems promising for patients with tumors of the middle and lower rectum who cannot undergo major surgery and for selected patients who refuse abdominoperineal resection.

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.

Second head and neck cancers following radiation therapy of T1 and T2 cancers of the oral cavity and oropharynx.

The risk of second cancer in the head and neck region following definitive radiation therapy was evaluated among 600 patients who were treated for T1 and T2 cancers of the oral cavity and oropharynx at the Henri Mondor hospital between January 1970 and March 1987. Seventy-five patients (12.5%) were managed with external irradiation only, 243 (40.5%) with RT and Iridium 192, and 282 (47%) with Iridium 192 alone. One hundred fifteen patients (19%) developed a second cancer from 3 to 183 months after initial therapy (median: 32 months), including 69 patients (11.5%) in whom the second malignancy was diagnosed in the head and neck region. An increased and constant actuarial risk of development of second head and neck cancer was found (2.7%/year of observation). Univariate analysis showed that age, sex, stage, and modality of the initial treatment did not influence the risk of second head and neck cancer; there was a greater risk of second head and neck malignancy for those patients with soft palate carcinoma (p less than 0.05). Multivariate analysis revealed that the only group of patients who developed a second head and neck cancer more frequently were those who were irradiated with Iridium 192 only (p = 0.0076). There was a trend toward a greater risk of second head and neck malignancy for those with soft palate carcinoma (p = 0.059). Radical treatment of the second head and neck malignancy by surgery and/or re-irradiation was performed for 67% of patients. Patients initially treated by Iridium 192 only could undergo salvage treatment more often than those who previously received external beam radiotherapy (79% vs 53%, p = 0.02). The overall 2-year and 5-year survivals after the diagnosis of the second head and neck cancer were 32% and 10%, respectively.

External irradiation prior to conservative surgery for breast cancer treatment.

From 1981 to 1987, 138 patients with breast cancer unsuitable for primary tumorectomy received initial external radiotherapy (45 Gy/25f/35d) in order to reduce the tumor volume so that secondary limited surgery could be performed. There were 81 T2 and 57 T3. Fifty-seven percent of the patients had a tumor larger than 4.5 cm. After completion of the radiotherapy, 22 patients (16%) showed no more evidence of a tumor either clinically or radiologically and received a boost of 25 Gy. In 52 cases (38%) the tumor regression allowed for secondary tumorectomy followed by a boost of 20 Gy. Sixty-four patients (46%) showed either little or no tumor regression: radical surgery was performed in 14 cases (10%) and high dose boost curietherapy (37 Gy) in the 50 (36%) remaining patients who refused mastectomy. Breast conservation in good condition was thus obtained in 74 patients (54%). Sufficient tumor regression to allow secondary tumorectomy was more often observed in T2 than in T3, in poorly differentiated tumors or mucinous type, and in tumor with well defined mammographic aspects. Actuarial 5-year local control and disease-free survival rates after limited surgery were, respectively, 90% and 73%. No particular complications were observed after secondary tumorectomy. This therapeutic approach is encouraging in patients with large T2 and T3 breast tumors, but a longer follow-up is required to assess definitive conclusions.

Iridium-192 curietherapy for T1 and T2 epidermoid carcinomas of the floor of mouth.

From 1970 to 1986, 117 patients with T1 (47) or T2 (70) epidermoid carcinomas of the floor of the mouth (SCC) were treated by iridium-192 implantation (192 Ir). The dose was prescribed according to the Paris System and varied over those years. Follow-up information was available on 116 patients. There were 46 T1N0, 47 T2N0, and 23 T2N1-3. Neck management varied for the 93 N0 patients consisting of surveillance (24 T1, 17 T2) or elective neck dissection (22 T1:all pN-, 30 T2: 20 pN-, 10 pN+). Cause specific survival rates were 94% for T1N0, 61.5% for T2N0, and 28% for T2N1-3 at 5 years. Primary local control was 93.5%, 74.5%, and 65%, respectively, and 98%, 79%, and 65% after salvage. Patients with gingival extension or a tumor size over 3 cm (T2b) had a local control of 50% (9/18) and 58% (15/26), respectively. Nodal control was 93.5% for Stage I, 85% for Stage II, and 48% for T2N1-3 patients. There was no difference in nodal control with regard to treatment policy for Stage I-II patients. There were few complications including three deaths: two from surgery and one from 192 Ir. Nodal status, tumor size defined as T1, T2a (less than or equal to 3 cm), T2b (greater than 3 cm), and gingival extension were the only independent prognostic factors. The management of T1N0 and T2N0 SCC by 192 Ir to a dose of 65 or 70 Gy, using the Paris System, is recommended for lesions 3 cm or less and without gingival extension.

Iridium 192 implantation of T1 and T2 carcinomas of the mobile tongue.

Between 1970 and 1986, 166 patients with T1 or T2 epidermoid carcinomas of the mobile tongue were treated by iridium 192 implantation (70 T1N0, 83 T2N0, 13 T1-2 N1-3). Five-year actuarial survival was 52% for T1N0, 44% for T2aN0, and 8% for or T1-2 N1-3. Cause specific survivals were 90%, 71%, and 46%, respectively. Local control was 87% for both T1N0 and T2N0, and 69% for T1-2 N1-3. Seven of 23 failures were salvaged by surgery, increasing local control to 96% for T1 and 90% for T2. Thirty-six patients developed a minor or moderate necrosis (16% T1, 28% T2). Half of these involved bone but only five required surgical intervention. Both local control (LC) and necrosis (nec) increased with increasing dose but improvement beyond 65 Gy is minimal (less than or equal to 60 Gy: LC = 78% nec = 13%; 65 Gy: LC = 90% nec = 29%; greater than or equal to 70 Gy: LC = 94% nec = 23%). For N0 patients, neck management consisted of surveillance (n = 78), elective neck dissection followed with external irradiation for pathologically positive nodes (n = 72), or irradiation (n = 3). Clinically positive nodes (13 patients) were managed by either neck dissection followed by external irradiation if pathologically positive (n = 10) or irradiation alone (n = 3). Regional control was 79% for N0 patients, improving to 88% after surgical salvage, and was 9/13 for N1-3 patients. We recommend that T1 and T2 carcinomas of the mobile tongue be treated by iridium 192 implantation to deliver 65 Gy. Mandibular necrosis should be reduced by using an intra-oral lead-lined dental mold.

Venocclusive disease of the liver after allogeneic bone marrow transplantation in man.

One hundred and fifty-one consecutive patients underwent allogeneic bone marrow transplantation (B.M.T.) following high-dose chemotherapy and single dose total body irradiation (T.B.I.) for hematologic malignancies between September 1980 and December 1985. All patients included in this study were treated using a 60 Co beam to deliver a prescribed dose of 10 Gy to the mid-plane of the abdomen. Total body irradiation was performed the day before B.M.T. The mean instantaneous dose-rate was 3.5 cGy/min (range: 2.6 to 4.7). The real dose received was measured using thermoluminescent dosimeters (lithium borate). The difference between the doses delivered to the liver and to the mid-plane of the abdomen did not exceed 5%. The mean real dose delivered to the reference point was 10 Gy (range 8.3 to 11.7). Ninety five per cent of the patients received a dose ranging from 9.1 Gy to 10.9 Gy. High-dose cyclophosphamide was given to 126 patients with a "standard-risk" of relapse (60 mg/kg on day 5 and 4 before B.M.T.). Chemotherapy was intensified by the addition of other drugs in 25 patients with "higher-risk" of relapse. We analyzed the effect of the following pretransplant characteristics on the subsequent posttransplant development of V.O.D.: age, sex, ASAT and/or ALAT before conditioning regimen, diagnosis and status of malignant disease, history of liver disease, interval between diagnosis of hematologic malignancy and B.M.T., conditioning regimen (i.e., classical or intensified) and dose delivered to the liver during T.B.I. Seventeen patients were classified as having clinical V.O.D. giving a prevalence of 11.2%. In the first 2 months following B.M.T., death occurred respectively in 9 of 17 (53%) and 23 of 134 (17%) patients with and without clinical V.O.D. Univariate analysis showed that four characteristics were significantly related to an increased prevalence of V.O.D.: sex (11/62 females vs 6/89 males; p less than 0.05); history of liver disease (7/28 vs 10/117 patients without antecedent; p less than 0.01); ASAT and/or ALAT levels greater than 1.5 upper normal limit (11/49 vs 6/102 patients with levels less than 1.5; p less than 0.01) and intensified conditioning regimen (6/25 vs 11/126 patients with classical regimen; p less than 0.05). The conditioning regimen and history of liver disease were highly correlated to transaminases levels. Only two factors, transaminases levels and female sex, remained significantly associated with V.O.D. after multivariate analysis.