RESUMO
We tested the efficacy of the hypoxic cell sensitizer misonidazole in conjunction with intraoperative electron beam radiation therapy (IORT) and external beam irradiation in patients with locally advanced, nonmetastatic adenocarcinoma of the pancreas. Misonidazole was delivered intravenously (IV) at a dose of 3.5 g/m2 in conjunction with IORT of 1,500 to 2,000 cGy to the pancreas. Additional external beam radiation as administered to 4,960 cGy. The study was based on the premise that the effect of misonidazole would be maximized when a high dose of the drug was administered and, thus, high hypoxic cell sensitization could be obtained when using a high single dose of radiation where the hypoxic fraction would be expected to dominate in the survivors. In a nonrandomized study of 41 patients treated with misonidazole and 22 without, the 1-year local control was 67% and 55%, and 1-year survival was 50% and 77%, respectively. Although there was a bias towards larger tumors in the patients treated with the sensitizer, we were unable to demonstrate an advantage to misonidazole in this clinical situation.
Assuntos
Adenocarcinoma/cirurgia , Misonidazol/uso terapêutico , Neoplasias Pancreáticas/cirurgia , Análise Atuarial , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Terapia Combinada , Seguimentos , Humanos , Período Intraoperatório , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/radioterapia , Tomografia Computadorizada por Raios XRESUMO
Beginning in December 1975, at the Massachusetts General Hospital (MGH) patients with rectal carcinomas thought to be at high risk of local recurrence after potentially curative surgical resection, were entered on a treatment protocol of high dose postoperative radiation therapy. Treatment was given with X rays of 10 MeV, generally using a four-field box technique to a dose of 4500 cGy with a boost to 5040 cGy or higher when the small bowel could be excluded from the reduced field. One-hundred sixty-five patients who began their radiation therapy between December 1975 and December 1982 were entered into the study. The median age was 65 years. The median follow-up in the survivors was 56 months, with a minimum follow-up of 17 months. All but 10 patients were followed for more than 2 years. Of the entire group, the actuarial 5-year survival was 53%, with survival of 71% in patients with Stage B-2, 39% in Stage C-2, and 17% in Stage C-3. Local failure was seen in 5/53 patients with Stage B-2 disease and 0/7 of patients with Stage B-3 disease. In patients with positive lymph nodes, local failure occurred in 2/10 (20%) of patients with Stage C-1, 16/77 (21%) of Stage C-2, and 8/15 (53%) of patients with Stage C-3 disease. Compared to previous series of surgery alone, the local failure rate has been decreased by more than one-half in all patients, except those with Stage C-3. Efforts to maximize the radiation doses in all stages should be made to minimize local failure. For Stage C-3, newer strategies such as intraoperative radiation therapy should be employed to decrease the continuing high incidence of failures.
Assuntos
Neoplasias Retais/radioterapia , Idoso , Terapia Combinada , Seguimentos , Humanos , Prognóstico , Neoplasias Retais/cirurgiaRESUMO
A retrospective review of all patients undergoing radiotherapy for carcinoma of the colon, pancreas, stomach, small bowel and bile ducts, lymphomas of the stomach, and other GI sites and retroperitoneal sarcomas was completed to assess the effects of secondary irradiation on the kidney. Eighty-six adult patients were identified who were treated with curative intent, received greater than 50% unilateral kidney irradiation to doses of at least 2600 cGy and survived for 1 year or more. Following treatment, the clinical course, blood pressure, addition of anti-hypertensive medications, serum creatinine and creatinine clearance were determined. Creatinine clearance was calculated by the formula: creatinine clearance equals [(140-age) X (weight in kilograms)] divided by (72 X serum creatinine) which has a close correlation to creatinine clearances measured by 24 hr. urine measurements. The percent change in creatinine clearance from pre-treatment values was analyzed. Of the thirteen patients with pre-radiotherapy hypertension, four required an increase in the number of medications for control and nine required no change in medication. Two patients developed hypertension in follow-up, one controlled with medication and the other malignant hypertension. Acute or chronic renal failure was not observed in any patient. The serum creatinine for all 86 patients prior to radiation therapy was below 2 mg/100 ml; in follow-up it rose to between 2.2-2.9 mg/100 ml. in five patients. The mean creatinine clearance for all 86 patients prior to radiotherapy was 77 ml/minute and for 16 patients with at least 5 years of follow-up it was 62 ml/minute. The mean percent decrease in creatinine clearance appeared to correspond to the percentage of kidney irradiated: for 38 patients with only 50% of the kidney irradiated the mean percent decrease was 10%, whereas for 31 patients having 90 to 100% of the kidney treated the decrease was 24%. Although physiologic changes were seen in patients receiving 50% or more unilateral kidney irradiation, the development of significant clinical sequelae was limited to one patient.
Assuntos
Neoplasias Abdominais/radioterapia , Rim/efeitos da radiação , Radioterapia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Records of 98 patients undergoing surgery for squamous cell carcinoma of the vulva between 1960 and 1982 were analyzed to evaluate and develop treatment policy. There were 32, 34, 26, and 6 patients in FIGO stages I-IV, respectively. Eighty-six patients underwent radical vulvectomy, 8 patients underwent less extensive procedures, and 4 underwent more extensive procedures. Eighty-seven patients underwent inguinal node dissection, and 40 underwent pelvic node dissection as well. Eight patients received external beam irradiation. Actuarial 5-year survival was 57%. Age, tumor size, FIGO (clinical) stage, surgically determined T and N stages, tumor differentiation, lymph vessel invasion, extent of surgical procedure, and adjuvant irradiation were analyzed to determine their effects on local control, freedom from distant metastases, and survival, using single variable and multivariate analysis. Local control was significantly related to FIGO stage; freedom from distant metastasis was significantly related to surgical N stage, tumor size, and surgical T stage; survival was significantly related to surgical N stage, tumor size, surgical T stage, age, and lymph vessel invasion. Metastatic involvement of inguinal lymph nodes was significantly correlated with tumor size and differentiation. Of 87 evaluable patients, 33 had inguinal node involvement, and of these, 17 developed recurrent disease. All 7 patients with pelvic node metastases had positive inguinal nodes, and all died; the cause of death could be determined in 5, of whom 4 manifested distant metastases. Pelvic lymphadenectomy conferred no survival benefit in this series, even in the presence of positive inguinal nodes. Local vulvar recurrence is a significant problem in patients with positive inguinal nodes, and postoperative irradiation should be directed to this area in these patients. Patients with vulvar recurrences, especially those occurring at least 2 years after surgery, can be successfully salvaged, and should therefore be treated aggressively.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Vulvares/cirurgia , Adulto , Fatores Etários , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Terapia Combinada , Feminino , Humanos , Tempo de Internação , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Vulvares/mortalidade , Neoplasias Vulvares/patologiaRESUMO
Twenty-eight patients with sarcomas of the uterine corpus were followed at least 22 months or until death. All underwent laparotomy, eleven had radiation therapy, and six had chemotherapy. Three year actuarial survival was 24%, and three year actuarial local control was 36%. Multivariate analysis demonstrated that, as with sarcomas at other sites, the most important factors influencing survival were grade (P = 0.020) and stage (P = 0.022). For local control, multivariate analysis indicated the most important factors to be stage (P = 0.001) and radiation TDF (P = 0.01). Of 21 failures, 16 involved the pelvis, seven involved the upper abdomen, and 11 involved distant sites. The importance of both local and distant disease control is emphasized.
Assuntos
Sarcoma/cirurgia , Neoplasias Uterinas/cirurgia , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Leiomiossarcoma/radioterapia , Leiomiossarcoma/cirurgia , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/radioterapia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Prognóstico , Sarcoma/radioterapia , Neoplasias Uterinas/radioterapiaRESUMO
Since 1978 we have used electron beam intraoperative radiation therapy (IORT) to deliver higher radiation doses to pancreatic tumors than are possible with external beam techniques while minimizing the dose to the surrounding normal tissues. Twenty-nine patients with localized, unresectable, pancreatic carcinoma were treated by electron beam IORT in combination with conventional external radiation therapy (XRT). The primary tumor was located in the head of the pancreas in 20 patients, in the head and body in six patients, and in the body and tail in three. Adjuvant chemotherapy was given in 23 of the 29 patients. The last 13 patients have received misonidazole (3.5 mg/M2) just prior to IORT (20 Gy). At present 14 patients are alive and 11 are without evidence of disease from 3 to 41 months after IORT. The median survival is 16.5 months. Eight patients have failed locally in the IORT field and two others failed regionally. Twelve patients have developed distant metastases, including five who failed locally or regionally. We have seen no local recurrences in the 12 patients who have been treated with misonidazole and have completed IORT and XRT while 10 of 15 patients treated without misonidazole have recurred locally. Because of the shorter follow-up in the misonidazole group, this apparent improvement is not statistically significant. Fifteen patients (52%) have not had pain following treatment and 22 (76%) have had no upper gastrointestinal or biliary obstruction subsequent to their initial surgical bypasses and radiation treatments. Based on the good palliation generally obtained, the 16.5-month median survival, and the possible added benefit from misonidazole, we are encouraged to continue this approach.
Assuntos
Neoplasias Pancreáticas/radioterapia , Adulto , Idoso , Braquiterapia , Elétrons , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Misonidazol/uso terapêutico , Recidiva Local de Neoplasia , Cuidados Paliativos , Neoplasias Pancreáticas/mortalidade , Radiação IonizanteRESUMO
Between 1972 and 1981, the Eastern Cooperative Oncology Group completed two major studies of advanced Hodgkin's disease. The first trial EST 2472, demonstrated that the five-drug combination of carmustine (BCNU), cyclophosphamide, vinblastine, procarbazine, and prednisone (BCVPP) is an effective alternative to mechlorethamine, vincristine, prednisone, and procarbazine (MOPP) chemotherapy. Although the complete remission (CR) rate for BCVPP (77%) was similar to that for MOPP (73%) in this randomized trial, the choice of induction chemotherapy significantly influenced CR duration. Patients achieving CR with BCVPP had a significantly greater disease-free survival than those who achieved CR with MOPP (65% vs 50%, respectively, at 5 years, P = 0.02). Overall survival is not different at this time between patients who received BCVPP and those who received MOPP. BCVPP produced significantly less gastrointestinal toxicity and neurotoxicity than MOPP. There was no influence on CR duration or survival with maintenance chemotherapy or BCG immunotherapy when compared to no further treatment. In the second trial, EST 1476, there was only a 58% CR rate with six cycles of low-dose bleomycin-MOPP induction chemotherapy. Complete responders and continuing partial responders were then randomized to receive either non-cross-resistant chemotherapy with doxorubicin, bleomycin, vinblastine, and DTIC (dacarbazine) (ABVD) or low-dose radiotherapy to all sites of pretreatment involvement except bone marrow. Fifty percent of the partial responses were converted to CR with either ABVD or radiotherapy consolidation. The overall CR rate at the end of consolidation was 68%. At the present time, there is no significant difference in disease-free or overall survival between ABVD and radiotherapy.
Assuntos
Antineoplásicos/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Adulto , Carmustina/administração & dosagem , Ensaios Clínicos como Assunto , Ciclofosfamida/administração & dosagem , Quimioterapia Combinada , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/radioterapia , Humanos , Masculino , Mecloretamina/administração & dosagem , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Vimblastina/administração & dosagem , Vincristina/administração & dosagemRESUMO
Fifty-two patients with stage III or IV nodular mixed lymphocytic-histiocytic lymphoma (NM) were entered on a prospective randomized trial comparing cyclophosphamide-prednisone (CP) to either COPP (cyclophosphamide, vincristine, procarbazine, prednisone) or BCVP (BCNU, cyclophosphamide, vincristine, prednisone). The COPP regimen utilized in this Eastern Cooperative Oncology Group (ECOG) trial was similar to the four-drug regimen C-MOPP reported by the National Cancer Institute to achieve prolonged relapse-free survival in this histology. No significant differences in complete response rates, response duration, or overall survival were noted among the three regimens. A pattern of continuous late relapse was observed for all three chemotherapy programs. Although 11 of the 18 (61%) COPP patients achieved a complete response, only 3/11 (27%) remain disease-free with a median follow-up of over 3 yr. However, two of these three long-term complete responders have died with no clinical evidence of recurrent disease. The COPP patients received 84% of the calculated ideal doses of cyclophosphamide and 78% of the ideal dosage of procarbazine. Grade 3-4 hematologic toxicity was noted in 22% of the COPP group, 36% with BCVP, and 0% for the CP patients. We were unable to confirm the ability of COPP to achieve durable complete remissions in NM lymphoma. The cyclophosphamide-prednisone combination was equally effective when compared with COPP and BCVP, but produced minimal toxicity.