Initial Extent Of Disease Research Articles

Results of treatment of advanced-stage Burkitt's lymphoma and B cell (SIg+) acute lymphoblastic leukemia with high-dose fractionated cyclophosphamide and coordinated high-dose methotrexate and cytarabine.

To address the problem of historically poor results in the treatment of children with advanced-stage Burkitt's lymphoma and B cell (SIg+) acute lymphoblastic leukemia (ALL), an intensive chemotherapy regimen was devised using the most effective single agents in high-dose short courses. Treatment commenced with a fractionated schedule of intravenous (IV) cyclophosphamide (300 mg/m2 every 12 hours for six doses) followed immediately by Adriamycin (50 mg/m2) and vincristine (1.5 mg/m2) with combined intrathecal (IT) methotrexate and cytarabine. Predictably, this treatment produced virtually complete disappearance of all tumor and profound myelosuppression. Immediately on hematologic recovery, IV high-dose methotrexate (1,000 mg/m2 over 24 hours) followed by IV cytarabine (400 mg/m2 over the next 48 hours) was administered with leucovorin rescue and repeated IT treatments. The treatment sequence described above is repeated four times, with the dose of cytarabine doubled in succeeding courses, up to 3,200 mg/m2. The entire planned therapy required approximately 24 weeks. Since 1981, we treated a total of 29 children with this approach, 19 of whom had massive unresectable intraabdominal tumor. According to initial extent of disease, 17 were classified as stage III, four as stage IV non-Hodgkin's lymphoma (NHL), and eight as B cell ALL. Eight of the 12 patients with stage IV NHL or B cell ALL had initial involvement of the CNS. Twenty-seven of 29 patients (93%) attained a complete remission. Fourteen of 17 stage III NHL patients remain disease free, for periods ranging from 3+ months to 4 1/2+ years. The actuarial estimate of the proportion of stage III patients remaining disease free at 2 years is 81%. Results in patients with initial involvement of the CNS and/or marrow are much less favorable, with only two of ten patients who attained remission apparently being cured. In addition to stage, the initial serum lactic dehydrogenase (LDH) level emerged as a prognostic indicator, higher levels (over 1,000 IU/L) being associated with the worst prognosis (P less than .05). Major toxicity consisted of severe hematopoietic suppression and febrile episodes associated with neutropenia. We conclude that this treatment is highly effective for advanced-stage Burkitt's tumors in children free of initial CNS involvement.

Long-term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma.

We assessed the results of treatment in 283 patients with lung or bone metastases from differentiated thyroid carcinoma who were followed for up to 40 yr (median, 44 months) after the discovery of the metastases. The survival rates from the time of discovery of the metastases were 53% at 5 yr, 38% at 10 yr, and 30% at 15 yr; 156 patients died. Multivariate analysis revealed that only 4 variables had an independent prognostic significance for survival. They were extensive metastases, older age at discovery of the metastases, absence of radioiodine uptake by the metastases, and moderately differentiated follicular cell type. The site of metastases (lung or bone) was not a prognostic factor for survival after treatment of metastatic disease. Remission was achieved in 79 patients after metastases were found. The only predictive factor for 5-yr disease-free survival after treatment of metastases was the initial extent of disease. Our results suggest that the aim of management should be to detect and treat metastases in patients with thyroid cancer as early as possible.

Computed tomography in the staging of small cell lung cancer: Implications for combined modality therapy

Computed tomography of the thorax and abdomen, from the thoracic inlet to the renal hila, was performed as part of initial staging in 51 patients with small cell carcinoma of the lung (SCCL). The computed tomographic (CT) scans were repeated after completion of chemotherapy, as part of routine restaging and assessment of response to therapy. To identify the ways in which CT scanning uniquely benefited evaluation of initial disease extent in comparison to other diagnostic studies exclusive of CT scan, all diagnostic and clinical data were reviewed. CT scan identified more advanced intrathoracic disease than chest radiography in 82% of patients. Mediastinal node involvement not appreciated by chest radiography was seen in 61% of patients. Adrenal and retroperitoneal node involvement, not suspected by other studies, was identified by CT scan in 31% and 12% of patients, respectively. Thirty percent of the patients staged as limited disease (LD) were advanced to extensive disease (ED) by CT scan findings. While confirmation, by biopsy, of positive CT findings was not consistently accomplished, restaging CT scans provided indirect confirmation by displaying improvement or worsening that correlated with disease regression or progression. Thoraco-abdominal CT scanning more accurately identifies the extent of small cell carcinoma than other imaging procedures. This has important implications for reporting results by extent of disease. In addition, CT more accurately identifies the magnitude of intrathoracic primary and nodal tumors, which may influence the choice and conduct of local treatment-surgery and/or radiation therapy-in combination with systemic chemotherapy.

Long term prognosis in ulcerative colitis--based on results from a regional patient group from the county of Copenhagen.

The prognosis of ulcerative colitis including survival, colectomy rate, activity of disease, and working capacity was estimated from a follow up study of 783 patients with ulcerative colitis comprising all patients from the county of Copenhagen, except for the island of Amager, diagnosed between 1960 and 1978. The period of observation ranged from one to 18 years with a median of 6.7 years for the clinical observations, eight years for survival and 11.6 years for the occurrence of large bowel cancer. The follow up was 100% for both survival and cancer. The survival rate in women did not differ from that in the general population. In men over 40 years of age at diagnosis a slight excess mortality was found, but only in the year of diagnosis (2.1%) and the following year (1.5%). Colonic cancer was seen in only seven out of the 783 patients, corresponding to an annual risk of 0.07% and a cumulative risk after 18 years with ulcerative colitis of 1.4% (95% confidence limits, 0.7-2.8%) independent of the initial extent of disease. The colectomy rate was 9.6% in the year of diagnosis. The cumulative 10- and 18-year colectomy rate was 23% and 31%, respectively. After three years from diagnosis the capacity for work both in those subject to resection and treated conservatively did not differ significantly from that in the background population. At any time about 50% of the patients were without symptoms, in about 30% the disease activity was low and in about 20% moderate or high. Most patients, however, differed in activity from one year to another and almost all patients (97%) experienced at least one relapse during a 10 year time period.

Non-Hodgkin's lymphoma of the stomach.

Thirty-seven patients with non-Hodgkin's lymphoma of the stomach were treated with curative intent by several single and combined modality regimens. Twenty-two patients presented with stage IE and 15 with stage IIE disease. All but three patients underwent laparotomy. Of all diagnostic procedures used, x-ray of the upper gastrointestinal tract proved to be most helpful in diagnosing malignant lesions (87%). Gastric cytology was suspicious or diagnostic of malignancy in 35% of the patients. Twelve of 34 evaluable patients (35%) developed recurrence. Distant metastases (75%) was the most common mode of failure. The recurrence rates varied by the type of therapy and also the extent of initial disease. Four of 12 patients (33%) were salvaged with retreatment. The 5-year actuarial no evidence of disease survival for the entire group was 61% (stage IE-57%; stage IIE-67%). Patients receiving combined modality therapy had significantly (p = less than 0.05) higher survival than patients treated with single modality treatment. Three of 29 patients (10%) died of surgical complications after gastrectomy. Radiation treatment was well tolerated. Our data and a critical review of the literature do not support the reportedly high incidence of gastric perforation after radiation treatment. We recommend the use of adjuvant radiation for stage IE and adjuvant radiation plus chemotherapy for stage IIE gastric lymphoma.

Advanced Metastatic Testicular Cancer: The Need for Reporting Results According to Initial Extent of Disease

During an 8-year period 63 consecutive patients were treated for the first time for extensive metastatic nonseminomatous testicular cancer. Four patients did not respond sufficiently to chemotherapy to be considered surgical candidates, while 59 underwent surgical resection of retroperitoneal disease. Of these 59 patients 19 had concomitant wedge resection of associated pulmonary disease and 9 had a planned subsequent resection of residual pulmonary disease. Of the 63 patients 16 had stage B3 disease alone and 47 presented with pulmonary metastases associated with varying degrees of retroperitoneal disease. The most important determinant for survival was extent of pulmonary disease. Of 17 deaths 14 occurred among patients presenting with extensive pulmonary disease. Patients with minimal to moderate pulmonary disease have done well regardless of the extent of coexistent abdominal disease, 24 of 27 (89 per cent) remaining in sustained complete remission. Of 16 patients with massive palpable abdominal disease (B3) without coexistent pulmonary metastases 15 (94 per cent) survived free of tumor. The combination of extensive pulmonary and abdominal disease with or without liver involvement has a poor prognosis, with only 35 per cent of these patients remaining in sustained complete remission. Preoperative combination chemotherapy with platinum, vinblastine sulfate and bleomycin has improved survival free of tumor in this group compared to other combinations not including platinum (47 compared to 20 per cent) but the results in this selected group of patients are significantly worse than those seen for all other patients with lesser extent of disease. Tumor recurrence more than 9 months after achieving complete remission has not been noted during followup to 10 years.A plea is made for cases of advanced disease (B3 and/or C) to be reported according to the extent of pulmonary disease as well as the associated abdominal disease, since analysis of these data reveals striking differences in patient survival, ranging from 100 to 35 per cent according to subgrouping.

Treatment of early vocal cord carcinoma: A comparison of apples and apples

Radiation therapy, hemilaryngectomy, and even cordectomy will cure a very large percentage of patients with early vocal cord cancer and preserve the voice. However, hemilaryngectomy and cordectomy are conceded by most surgeons to usually produce a poorer voice, compared to radiation therapy, and the operations are restricted to certain anatomical distributions. Those surgeons advocating hemilaryngectomy or cordectomy have compared their results with radiation therapy series which include a proportion of patients with lesions not suitable for voice-sparing operations. One hundred and thirty-nine patients with T 1-2 carcinoma of the vocal cords with a 2-15 year follow-up, who were treated initially by radiation therapy, were analyzed in detail by initial extent of disease. Patients were identified whose lesions were anatomically suitable for hemilaryngectomy or cordectomy, and results for these patients compared to operative results. Since the curative results with voice sparing by irradiation were at least equal, and since the quality of the voice is thought to be much better, there is little justification for recommending a major operation except in specific situations. Lesions initially suitable for voice-sparing operations which subsequently recur after irradiation can usually be treated by a voice-sparing operation.

Computed tomography of colon carcinoma.

A review was made of 80 computed tomographic (CT) examinations of the abdomen and/or pelvis in patients with known carcinoma of the colon. These studies were obtained for evaluation of the initial extent of disease, delineation of the progression of disease, determination of the response to therapy, or location of possible recurrence. The sites of metastases are reported. The results support the routine use of CT in patients with colon carcinoma.

In situ carcinoma of the vocal cords

Eighty-one patients with preinvasive carcinoma of the vocal cord, seen over a thirteen year period, were reviewed histologically and analyzed for response to treatment. Sixty-seven cases were clinically T1 and fourteen cases T2 (by virtue of extension of disease beyond the vocal cord). All patients had mobile cords. Histological criteria for in situ carcinoma and the spectrum of microscopic patterns are presented. Sixty-nine patients were treated by external beam radiotherapy--the remainder by a variety of surgical procedures. Five and ten year actuarial, recurrence-free rates 83% and 75%, respectively for the group treated by irradiation. No difference in local control was observed when analyzed for: 1) dose response, 2) initial extent of disease, 3) treatment plan, or 4) histologic diagnosis. Analysis of failures reveals that 15/17 patients with local failure were salvaged, eleven of these patients requiring laryngectomy. Time to appearance of recurrence ranged from seven to one hundred and seven months.

In situ carcinoma of the vocal cords

Eighty-one patients with preinvasive carcinoma of the vocal cord, seen over a thirteen year period, were reviewed histologically and analyzed for response to treatment. Sixty-seven cases were clinically T1 and fourteen cases T2 (by virtue of extension of disease beyond the vocal cord). All patients had mobile cords. Histological criteria for in situ carcinoma and the spectrum of microscopic patterns are presented. Sixty-nine patients were treated by external beam radiotherapy--the remainder by a variety of surgical procedures. Five and ten year actuarial, recurrence-free rates 83% and 75%, respectively for the group treated by irradiation. No difference in local control was observed when analyzed for: 1) dose response, 2) initial extent of disease, 3) treatment plan, or 4) histologic diagnosis. Analysis of failures reveals that 15/17 patients with local failure were salvaged, eleven of these patients requiring laryngectomy. Time to appearance of recurrence ranged from seven to one hundred and seven months.

Conservative Treatment of Endometriosis: The Effects of Limited Surgery and Hormonal Pseudopregnancy

This study compares the effects of limited surgery or hormonal pseudopregnancy, or a combination of these two, upon fertility and the need for subsequent surgery with respect to the extent of the disease at the time of initial diagnosis in patients with endometriosis externa. Of the 61 patients who desired to enhance or preserve reproductive capacity, 20 patients became pregnant, for a pregnancy rate of 33%. The pregnancy rate in all categories, that is, those patients treated with pseudopregnancy, conservative surgery, and combined pseudopregnancy and surgery, was found to be in direct relationship to the initial extent of disease. In such patients, conservative surgery alone seemed to give the best results in the achievement of pregnancy. There seemed to be little difference between pseudopregnancy alone and conservative surgery in regard to the need for subsequent surgery after initial therapy, although there seemed to be a significantly greater chance for the need for subsequent surgery in patients receiving a combination of the two forms of therapy. The need for subsequent surgery after initial therapy in 80 patients increased in direct relationship to the initial extent of disease present, despite the form of therapy used. Fifty-nine other patients with endometriosis, who did not desire to preserve fertility and presented for relief of other symptoms, underwent initial "radical" therapy. Forty-six patients underwent complete operation, including removal of uterus, tubes and ovaries, and none required subsequent reoperation. Of the 13 remaining patients, who underwent incomplete surgical removal, leaving one or both ovaries in situ, 11 required subsequent reoperation for recurrent pelvic endometriosis.

Relapse in pulmonary tuberculosis.

Five hundred forty-three patients with bacteriologically confirmed pulmonary tuberculosis who successfully completed treatment were followed for 5 years to determine relapse rates and to see whether any factors could be said to predispose to relapse. Practically the entire treatment of these patients had been carried out in their homes. The cumulative relapse rate during a 5-year period was 11.60 per cent. Relapse rates were low during the first 2 years of follow-up. Of the various factors considered in the analysis, age, sex, initial extent of disease or cavitation, and presence of initial or emergent drug-resistant bacilli did not influence the relapse rate. Patients who achieved complete radiographic clearing at the time treatment was stopped and those who were regular in treatment had comparatively low relapse rates. Cured patients included in the study were asked to report at least once annually for a checkup, and immediately if they developed any symptoms suggestive of relapse. Only one fourth of the cases of relapse were detected during routine annual checkup; in the remaining cases, the patients attended ahead of the next due visit because of symptoms. This casts doubt on the utility of keeping cured patients under prolonged routine surveillance.

Survival in chronic myelogenous leukemia: influence of treatment and extent of disease at diagnosis.

A retrospective study was conducted on the survival of 178 patients with chronic myelogenous leukemia from January 1948 through December 1967. Through analysis of survival time, comparison has been made between a group of 50 patients treated with chemotherapy alone vs. a group of 84 patients treated with radiation therapy to the spleen and chemotherapy. No difference could be found in these two major therapeutic groups (median survival 31 months for both). Further analysis has been made to determine whether survival could be correlated to the initial extent of disease. Initial hemoglobin value, WBC, platelet counts, absolute blast count, spleen size, and selected combination of these factors showed no significant correlation with survival. Acute blastic transformation occurred in 60% of 117 patients. Infection as a cause of death was less frequent in patients with progressive disease without acute blastic transformation, while renal failure due to hyperuricemia and thromboembolic phenomena occurred more often in this group as compared with patients dying in acute blastic phase.