Experimental radiation pneumonitis studied with indium-111-pentetreotide.

OBJECTIVES: To understand the evolution of lung uptake of 111-In-Pentetreotide in a rat model of pulmonary radiation pneumonitis. METHODS: A 15 Gy 60-Co thoracic irradiation (1.4 Gy/min) was delivered to Wistar rats. Irradiated and control animals were studied during 8 weeks after irradiation. 24 hours after an injection of 111-In-pentetreotide (12-18 MBq), the uptake in the lung tissue (ULT), in the alveolar cells (UpC) and in different organs, was determined. Histological examinations were performed. RESULTS: ULT and UpC after irradiation increased significantly peaking at 4 weeks (ULT: 32.8 +/- 13.0 in 10(-5) of the injected dose versus 10.8 +/- 2.0 for control; and, UpC was 19.3 +/- 7.2 versus 7.3 +/- 4.1) and decreased afterwards. Pre-injection of cold octreotide decreased the lung uptake. This evolution parallels the histological changes: alveolitis with granulomas in the interstitium at 4 weeks followed by development of sites of interstitial fibrosis. These observations suggest that the uptake is due to activated cells, mainly macrophages within the granulomas and in the alveoli, expressing somatostatin receptors. CONCLUSION: 1) The uptake of 111-In-pentetreotide in injured lungs after irradiation, already described in man, was confirmed in a rat model; 2) our results suggest that it is possible to follow the evolution of radiation lung injury by using In-111-pentetreotide.

Efficacy of an ondansetron orally disintegrating tablet: a novel oral formulation of this 5-HT(3) receptor antagonist in the treatment of fractionated radiotherapy-induced nausea and emesis. Emesis Study Group for the Ondansetron Orally Disintegrating Tablet in Radiotherapy Treatment.

A significant number of patients who are receiving radiotherapy experience the distressing side effects of emesis and nausea. Although prophylactic antiemetics are often given to patients who are receiving single-fraction, high-dose radiotherapy to the abdomen, a survey has revealed that antiemetic prophylaxis is not routinely offered to those receiving fractionated radiotherapy. Hence there is a need for an effective treatment of emesis for use in this group of patients. Ondansetron is an effective and well-tolerated antiemetic, which is used for the prevention of both chemotherapy and radiotherapy-induced emesis and nausea. This agent has been developed as a novel freeze-dried oral formulation. Ondansetron orally disintegrating tablets (ondODT) disperse rapidly when placed on the tongue. As the tablet does not need to be swallowed with water, it is a particularly useful formulation for patients who have difficulty with swallowing or who do not feel able to drink. This study was undertaken to investigate the efficacy of ondODT in the treatment of established emesis and nausea induced by radiotherapy. Two doses of ondODT, 8 mg and 16 mg, were compared with placebo in patients who developed emesis and/or moderate/severe nausea after receiving fractionated radiotherapy to sites located between the thorax and the pelvis. The study showed that ondODT was clinically superior to placebo in treating emesis and nausea successfully over a 12-hour period after taking the medication. There were no statistically significant differences between the two doses of ondODT. In the 2 hours after taking the study medication, patients who received ondODT (8 mg and 16 mg) had significantly fewer emetic episodes compared with those who received placebo. They also experienced significantly less nausea. In conclusion, ondODT 8 mg is effective in the treatment of radiotherapy-induced emesis and nausea and provides an effective alternative to the conventional ondansetron tablet.

Response to second-line chemotherapy in patients with metastatic breast carcinoma previously responsive to first-line treatment: prognostic factors.

BACKGROUND: The aim of this retrospective study was to determine those prognostic factors associated with response to a second-line chemotherapy in patients with metastatic breast carcinoma (MBC) that was previously responsive to a first-line chemotherapy. METHODS: The 70 MBC patients studied had previously responded to a first-line chemotherapy, mainly anthracycline or anthracenedione-containing regimens. During first-line chemotherapy they had received treatment until the maximum response was obtained, at which time treatment was discontinued. Second-line chemotherapy regimens were of several types (48.5% with anthracycline). A study of prognostic factors associated with response to second-line chemotherapy was performed by univariate and multivariate analysis. RESULTS: Second-line chemotherapy achieved a 44% response rate, with a median response duration of 10 months. Survival was 13 months in the entire patient group, 22 months in responders, and 8 months in nonresponders. Univariate analysis identified seven factors related to patient response rate to second-line treatment. A better response rate to second-line chemotherapy was observed in patients with the following features: 1) chemotherapy free time (time between onset of metastatic disease and initiation of first-line) < 12 months (P = 0.03); 2) complete response to first-line chemotherapy (P = 0.013); 3) response duration to first-line chemotherapy > 14 months (P = 0.0001); 4) progression free interval (time between end of first-line treatment and initiation of second-line chemotherapy) > 11 months (P = 0.0001); 5) performance status at second-line treatment < 2 (P = 0.04); 6) tumor index at second-line chemotherapy < 4 (P = 0.05); and 7) treatment with an anthracycline-containing second-line regimen (P = 0.03). In multivariate analysis, only progression free interval was identified as being associated with response rate to second-line chemotherapy (P = 0.0001). CONCLUSIONS: Retained chemosensitivity appeared to be an important characteristic in patients responding to second-line chemotherapy.

Multimodal adjuvant treatment and liver transplantation for advanced hepatocellular carcinoma. A pilot study.

BACKGROUND: Orthotopic liver transplantation has been used in a large number of patients with primary liver cancer because it increases the possibilities of resection of large tumors. Despite isolated cases of prolonged survival, however, the results of liver transplantation for advanced tumors have been universally disappointing because of high rates of tumor recurrence. In an attempt to reduce the recurrence rate, a pilot study testing a multimodal adjuvant treatment in patients undergoing liver replacement for hepatocellular carcinoma was undertaken. METHODS: The treatment consisted of preoperative hepatic arterial chemoembolization (iodized oil, doxorubicin, and gelatin sponge) and radiotherapy (5 Gy in one fraction immediately before surgery), and postoperative systemic chemotherapy with mitoxantrone. Nine patients entered this study. The tumor was solitary in two cases (5 cm and 8 cm) and multifocal in seven cases (2-9 nodules, 3-9 cm). The postoperative TNM stages were II in one case, III in one case, and IVA in seven cases. RESULTS: Chemoembolization and radiotherapy were performed in seven cases each (five patients had both treatments). All patients underwent liver transplantation with conventional immunosuppression. One patient died of heart failure 4 days after surgery. The remaining eight patients received 4 to 10 courses of chemotherapy (mean 9). The main toxicity of chemotherapy was leucopenia. Two patients died of recurrence: one at 7 months and one at 11 months. Six patients are alive, five of them without evidence of disease, with a mean follow-up of 30 months (range 16-45) after liver transplantation. The 3-year actuarial survival is 64%. CONCLUSIONS: These results show that an aggressive adjuvant therapy can be used in association with liver transplantation in the treatment of advanced hepatocellular carcinoma without increased mortality and suggest that such a protocol could be effective in preventing tumor recurrence.

Interstitial iridium 192 for cutaneous carcinoma of the external nose.

Several implantation techniques useful for nasal skin carcinoma have been developed at the Henri Mondor Hospital in Créteil, France and are described in detail. Iridium 192 wires, 0.3 mm in diameter, are afterloaded into either supple plastic tubes or rigid needles implanted according to the rules of the Paris system. Dosimetry is performed by computer, based on either direct measurements of active lengths and spacing, orthogonal films or a tomogram oriented in the central plane of the implant. According to a recent review by the European Curietherapy Group of 468 implants, the optimal dose is 60 Gy. The overall failure rate was 2.6%. Indications for implantation and choice of technique, based on tumor size, site, and gross morphology are discussed.

Central nervous system relapses after bone marrow transplantation for acute lymphoblastic leukemia in remission.

This study defines the risk of central nervous system (CNS) relapse in patients undergoing bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL) in remission, with no posttransplant prophylactic CNS therapy. Ninety-two consecutive patients in complete remission received BMT for ALL (n = 82) or high-grade non-Hodgkin's lymphoma with poor prognostic factors at diagnosis (n = 10). Sixty-six patients received allogeneic BMT (Allo-BMT) and 26 patients, without an identical sibling, underwent autologous BMT (Auto-BMT). Fifteen patients had CNS involvement at diagnosis and underwent BMT in first remission. Eight patients experienced CNS relapse after BMT, corresponding to a probability of 11% at 3 years. Apart from a history of prior CNS involvement, no patient characteristic evaluated statistically influenced CNS relapse after BMT. The probability of CNS relapse was 5.5% for the 70 patients without history of CNS involvement and 27.5% for the 22 patients with prior CNS involvement. However, subgroup analysis showed that the increased risk of CNS relapse is mainly observed in Auto-BMT patients with history of prior CNS involvement, particularly in patients undergoing BMT in first remission (three of five Auto-BMT versus one of ten Allo-BMT). Taking into account the multiple factors which influence the occurrence and the treatment of CNS leukemia, the results on this retrospective study suggests that (1) for patients without CNS involvement at diagnosis and for whom BMT is performed in first remission, cranial irradiation before BMT and posttransplant prophylactic CNS therapy can be omitted because of the low probability of CNS relapse after BMT (3.4%), when total-body irradiation (TBI) is included in the conditioning regimen; and (2) the difference observed between Allo-BMT and Auto-BMT patients with previous CNS involvement and undergoing BMT in first remission could indicate that graft-versus-host leukemia acts even in the CNS in Allo-BMT patients.

Mediastinal diffuse large-cell lymphoma with sclerosis: a condition with a poor prognosis.

Twenty patients (17 women, three men) with mediastinal diffuse large-cell lymphoma with sclerosis are reported. At the time of diagnosis, the disease was confined to supradiaphragmatic areas in all patients but two, who had kidney involvement (seven were stage I, 11 were stage II, and two were stage IV). A B-cell phenotype was demonstrated in nine of the 11 cases that were analyzed for cell lineage. All patients received an anthracyclin-containing regimen followed by mantle radiotherapy. Analysis of pretreatment characteristics showed that only the extent of disease influences outcome. Moreover, achievement of complete remission (CR) after chemotherapy appears to be a major prognostic factor. Two-year survival was better in patients who reached CR after chemotherapy than in those who did not (100% versus 9%; p less than 0.0001). Overall 2-year and 7-year survival rates were 50% and 33%, respectively. Therefore, localized mediastinal large cell lymphoma with sclerosis should be considered a high-risk subtype of non-Hodgkin's lymphoma in which standard treatment approaches are unsuccessful.

Treatment of inflammatory breast cancer with combination chemotherapy and mastectomy versus breast conservation.

Twenty-six consecutive patients with nonmetastatic inflammatory breast cancer (IBC), were treated in a single institution using the same protocol, and all were followed for at least 48 months. The first phase of treatment consisted of two monthly cycles of combination chemotherapy with Adriamycin (Adria Laboratories, Columbus, OH), vincristine, cyclophosphamide and 5-fluorouracil. Local treatment was then undertaken using in all cases a cobalt 60 beam to deliver 45 Gy to the entire mammary gland and lymph-draining areas. Local treatment was completed either by mastectomy, or by conservation of the breast and interstitial irradiation of the primary tumor site. Chemotherapy was resumed after completion of local treatment for a total of 6 cycles. Metastatic disease occurred in 19 of 26 patients from 8 to 55 months; five patients are alive and free of disease from 48 to 81 months. Failure to control local disease or local recurrences was noted in two of ten patients undergoing mastectomy, and in seven of 13 patients with conservation of the breast. While this difference is not statistically significant we concluded that methods of breast conservation which limit the high dose volume to the tumor site do not assure local control in IBC. The median disease-free survival and overall survival of 12 and 31 months, respectively, are not satisfactory. Better systemic treatment is needed.

[Initial polychemotherapy in the treatment of cancers of the head and neck. The efficacy and tolerance of 2 nonrandomized combinations in 48 patients]. / Polychimiothérapie initiale dans le traitement des cancers des voies aérodisgestives supérieures. Efficacité et tolérance de deux associations non randomisées chez 48 patients.

Before loco regional treatment for head and neck cancer forty eight patients received one or the other of the following combined chemotherapy regimens: Regimen A (28 patients): high dosage methotrexate, bleomycin, cis-platin; regimen B (20 patients): common dosage methotrexate, bleomycin, hydroxyurea, vincristin. The effectiveness of regimen A seemed better than that of regimen B (46% responses versus 20%). This assessment must be accepted with caution, since, although the organization of treatment was strictly similar in the two groups, the study was not randomized, and there were noticeable differences between the two groups. Regimen B was associated with no toxicity. Regimen A was responsible for two fatalities. These two cases were linked to high dosage methotrexate. However, a combined chemotherapy regimen of type A with the high dosage methotrexate replaced by intermediate dosage methotrexate, seems feasible to us. Loco regional treatment was not impaired by initial chemotherapy with either regimen.

Early response to chemotherapy as a prognostic factor in Hodgkin's disease.

In 164 patients with Hodgkin's disease staged between 1973 and 1979 the response to the 3 initial cycles of multiagent chemotherapy was evaluated as a prognosticator of survival. Treatment of localized disease (Stages I, II, III1) consisted of 3 cycles of chemotherapy followed by subtotal nodal irradiation, including the splenic area in non splenectomized patients. Treatment of extended disease (Stage III2 and IV) consisted of 6 cycles followed by low-dosage radiotherapy of initial bulky disease. Five-year actuarial survival was 88% in Stage I, 80% in II, 100% in III1, 45% in III2 and IV. Chemotherapy-induced complete remission after 3 cycles (CH leads to CR) was associated with a favorable prognosis. Five-year survival of Stage III2 and IV patients was better in those who reached CH leads to CR than in those who did not (75% versus 25%; P less than 0.01). This relationship between CH leads to CR and five-year survival was confirmed in patients with localized disease, as shown in Stage II patients (respectively 97% versus 63%; P less than 0.05). Therefore the response to initial chemotherapy provides a new prognostic factor that may serve to delineate a "high-risk" group of patients. The latter deserve aggressive therapy while those in the favorable group would benefit from a less aggressive combined regimen that would minimize long-term complications.

[Treatment of malignant glioma. Apropos of 39 cases]. / Traitement des gliomes malins. A propos de trente-neuf cas.

Thirty-nine patients with malignant gliomas (36 glioblastomas, 3 astrocytomas grade III; age median 52.5) were treated after surgery by combination chemotherapy followed by irradiation. The median survival on the actuarial curve is 7 months. An attempt is made to evaluate each therapeutic modality by analysis of clinical and CT parameters.

[Prevention of sequelae after transcutaneous radiotherapy for epitheliomas of the oral cavity (author's transl)]. / Prévention des séquelles de la radiothérapie transcutanée des épithéliomas de la cavité buccale.

Close cooperation between the radiotherapist, surgeon, and patient is necessary in order to prevent sequelae following transcutaneous radiotherapy for epitheliomas of the oral cavity. The most effective therapeutic results combined with a minimum of sequelae are obtained by the use of a good irradiation technique, close supervision, careful treatment of any oral or dental affection, prescribing simple medications only, and stopping the use of tobacco and alcohol.

[Testicular choriocarcinomas masked by predominating seminomas]. / Les choriocarcinomes testiculaires masqueés par des séminomes prédominants

Testicular choriocarcinomas may be disguised by the histological appearance of pure seminomas with apparently normal HCG levels. As demonstrated by the 5 cases reported here, a definite diagnosis by further histological specimens, more often by the development of abnormal HCG levels, may be delayed. Early chemotherapy appears to offer the best chance to such patients. Suspicious signs: HCG levels at the limit of normal before castration, suspect histology (marked hypertrophy of the interstitial gland, zones of necrosis, an unusual clinical appearance with large lymph node lesions, an unusual course with early lymph node or metastic recurrences, may suggest the presence of choriocarcinoma and lead to routine chemotherapy.