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Biomedical subjects

W Lawrence

Publications and source records attributed to W Lawrence.

At least 73 records · Page 4Linked to original sources

Primary reexcision for patients with 'microscopic residual' tumor following initial excision of sarcomas of trunk and extremity sites.

Among 404 patients with primary tumors of extremity-trunk sites entered in the Intergroup Rhabdomyosarcoma Study (IRS) (1972 to 1984), 154 were placed in clinical group IIa, ie, with negative nodes but with "microscopic residual" (MR) disease, following the initial excisional (not biopsy) procedure. An elective reexcision of the area of the primary tumor (PRE) was performed in 41 of these patients within 35 days (mean interval, 14 days; SE, 0.9) with no intervening therapy. These procedures consisted of wider excision of the tumor "bed," resulting in a technical transfer of these patients from group IIa to group I, ie, complete excision. This reduced intensity of nonsurgical therapy (irradiation and chemotherapy). Among the 41 patients who underwent PRE, the 3-year survival estimate (Kaplan-Meier) was 91% (SE, 4%). This may be compared with the results in 113 patients who remained in group IIa, in which the 3-year survival estimate was 74% (SE, 4%). A second group for comparison consisted of the 73 patients with trunk/extremity tumors who were placed in group I after a single excisional procedure, ie, no PRE, in whom the 3-year survival estimate was 74% (SE, 5%). Recognized prognostic factors influencing survival in these groups were comparable, with the exception of tumor size, ie, the largest tumors (greater than or equal to 10 cm in diameter) were concentrated in groups I and IIa. When patients with tumors greater than or equal to 10 cm in diameter (9.7% of the total) were removed from all three study groups, patients undergoing PRE had longer survival duration estimates than patients in the control groups.

Humans↗

Management of biliary obstruction in patients with unresectable carcinoma of the pancreas.

Clinical and pathologic data from 73 patients with unresectable carcinoma of the pancreas treated from 1980 to 1987 were reviewed to evaluate the efficacy of biliary enteric bypass and percutaneous transhepatic biliary drainage (PTBD) in the treatment of malignant biliary obstruction. Fifty-two patients underwent biliary enteric bypass with no operative deaths and with a 15% operative morbidity. These patients had a median postoperative hospitalization of 12 days. Four patients (8%) eventually developed recurrent jaundice, and three of these were successfully treated with PTBD. The median survival for these 52 patients was 7 months. Twenty-one patients underwent PTBD with an 81% technical-success rate. These patients had a 33% early complication rate and a 33% in-hospital mortality. The median hospitalization was 13 days postdrainage. Of the 14 patients surviving the initial hospitalization, 86% developed late complications requiring 16 hospital admissions and ten emergency room visits for a total of 155 days of hospitalization. The median survival for those patients undergoing PTBD was 4 months from the time of diagnosis and 2 months from the time of catheter drainage. Surgical bypass offers excellent palliation for malignant biliary obstruction with extremely low morbidity and mortality in properly selected patients; PTBD is useful in the treatment of those patients with extensive disease, who are poor surgical candidates, or who have failed previous surgical drainage. There is a role for both of these palliative procedures in the management of patients with biliary obstruction from pancreatic cancer.

Adenocarcinoma↗

Intraoperative ultrasound of the liver affects operative decision making.

The surgeon operating upon patients with primary or metastatic hepatic cancers must determine if resection is feasible and, if it is, the magnitude of required resection. In an attempt to determine which tests best aid the surgeon in these determinations, the authors prospectively compared preoperative computed tomography (CT) of the liver and intraoperative ultrasound (IOU) in 42 patients with liver tumors who underwent 45 exploratory operations. The primary diseases included colorectal cancer metastases in 27 patients, hepatoma in 11 patients, and metastatic cancers of other origins in 4 patients. In the 42 patients there were 89 identified hepatic lesions that were confirmed to be malignant by resection, biopsy, or continued growth on follow-up CT. The sensitivity of either test for detecting these lesions was 69/89 (77%) for CT and 87/89 (98%) for IOU. Resection was not feasible in 13 patients. Five had extrahepatic disease, 4 had more nodules discovered by IOU, 3 were found by IOU to have involvement of all three hepatic veins by tumor and 1 patient had portal-vein invasion. Alternatively, in four patients tumors thought to involve all three hepatic veins by CT were shown to be free of at least one hepatic vein, thereby permitting resection. In one patient who had been previously operated upon, a tumor thought to involve the remaining right hepatic vein was seen to be free of the vein, also permitting resection. Regarding the extent of resection, IOU was also helpful. Lesser procedures than anticipated were proved possible by IOU in seven patients. A more extensive resection was shown to be necessary by IOU in two patients. Thus, IOU affected the operative management in 22 of 45 operative episodes (49%). It was conclude that IOU is superior to both preoperative CT and surgical exploration in assessing both the feasibility and the extent of resection required for primary and secondary hepatic cancers. In the authors' experience, IOU is the most sensitive indicator of number of lesions present in the liver. In addition, the ability of IOU to determine hepatic venous anatomy is a helpful adjunct in determining resectability of liver tumors.

Adult↗

Results of intensive therapy in children with localized alveolar extremity rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study.

Preliminary analyses of treatment results and prognostic factors from the first Intergroup Rhabdomyosarcoma Study (IRS I) suggested that alveolar histology and extremity site were among factors associated with an adverse outcome in clinical group I patients whose tumors had been completely resected. A high incidence of alveolar histology among the extremity tumors compounded the problem. These findings prompted an amendment to IRS II shortly after the study opened. Therapy for patients with alveolar extremity tumors in groups I and II was changed to more intensive repetitive pulse vincristine, dactinomycin, and cyclophosphamide (VAC) for 2 years. The outcome of 44 patients who received intensive therapy on IRS II is compared with a control series of 30 patients who were treated on IRS I. The control patients received standard VAC therapy for 2 years or VA for 1 year. Half of group I control patients received local radiotherapy, whereas none was given to group I intensive therapy patients. In both studies group II patients received radiotherapy to the primary tumor site and to identified positive regional lymph nodes. Compared with the control group, patients given more intensive therapy had a longer disease-free survival (DFS) (69% v 43% at 3 years), but this was of marginal significance (P = .06). The overall survival difference (77% v 57% at 3 years) was not significant (P = .23). Despite the limited statistical evidence, there is some indication that intensive therapy improved the prognosis of children with localized alveolar rhabdomyosarcoma (RMS).

Antineoplastic Combined Chemotherapy Protocols↗

Management of desmoid tumors.

Desmoid tumors are rare, being less than 0.03 per cent of all neoplasms. Because of scarcity of data and relatively small numbers of patients, optimal treatment remains controversial. In this report, our experience with 36 patients evaluated and treated from 1960 to 1987 is analyzed. The most common primary site was the wall of the chest (ten); eight tumors originated in the abdominal wall. Nine patients had a history of previous trauma, and eight of these were women. Thirty-two patients had wide local excision and two had amputations. Clear margins were obtained in only 22 patients despite an attempt at wide resection in all instances. With a mean follow-up period of 41 months and a median of 24 months, only one of 22 patients with negative histologic margins had recurrence of tumor. Among the 11 patients with positive margins, four received postoperative radiation therapy and two remain disease-free; of the seven remaining patients with positive margins, three had recurrences. One patient with unresectable disease was treated with tamoxifen with regression of tumor and remains alive 15 months later. These data suggest that the best treatment of desmoid tumors remains resection with a clear margin of normal tissue surrounding the tumor. Adjuvant radiotherapy did not appear to decrease the rate of local recurrence.

Actuarial Analysis↗

Clinical staging and treatment results in rhabdomyosarcoma of the female genital tract among children and adolescents.

From 1972 to 1984, 47 children and adolescents with primary tumors of the female genital tract were treated with eight different Intergroup Rhabdomyosarcoma Study (IRS I-II) protocols. These included patients with vaginal (28), uterine (ten), or vulval (nine) rhabdomyosarcoma or undifferentiated sarcomas. The mean age of patients with primary vaginal tumors was younger than 2 years. All were of the embryonal histologic subtype. The majority of these patients were treated with initial chemotherapy (vincristine, dactinomycin, +/- cyclophosphamide, +/- Adriamycin [(ADR) doxorubicin]) followed by delayed hysterectomy and/or partial vaginectomy. Among 26 patients with localized vaginal tumors, there have been six relapses resulting in one tumor-related death and one therapy-related death. The five patients with nonfatal relapse have been disease-free for from 2.5 to 6.5 years (mean, 4.4 years) since salvage therapy was commenced. The 19 patients without relapse have been continuously disease-free for 1.5 to 12 years (mean, 5.34 years: median, 6 years). No patient that received ADR initially relapsed. Ten patients, with a mean age greater than 13 years, had primary uterine sarcomas and were treated by the same chemotherapy regimens. Six with polypoid localized lesions, removed before chemotherapy, have remained disease-free for 2.5 to 6.5 years. Four, with more extensive local lesions or disseminated disease, treated with chemotherapy only, died 2 to 11 months from diagnosis. Nine patients with rhabdomyosarcomas of the vulva (age, 1-19 years) were managed by the same chemotherapy regimens +/- radiotherapy. Resection was carried out initially or after chemotherapy. Eight of these have been disease-free from 4 to 10 years (mean, 6.4 years); and one is alive with probable disease at 2.5 years.

Adolescent↗

Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01.

Data are presented from 1,166 patients with Dukes B and C carcinoma of the colon who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-01 between November 1977 and February 1983. Patients were randomized to one of three therapeutic categories: 1) no further treatment following curative resection (394 patients); 2) postoperative chemotherapy consisting of 5-fluorouracil, semustine, and vincristine (379 patients); or 3) postoperative BCG (393 patients). The average time on study was 77.3 months. A comparison between patients receiving postoperative adjuvant chemotherapy and those treated with surgery alone indicated that there was an overall improvement in disease-free survival (P = .02) and survival (P = .05) in favor of the chemotherapy-treated group. At 5 years of follow-up, patients treated with surgery alone were at 1.29 times the risk of developing a treatment failure and at 1.31 times the likelihood of dying as were similar patients treated with combination adjuvant chemotherapy. Comparison of the BCG-treated group with the group treated with surgery alone indicated that there was no statistically significant difference in disease-free survival (P = .09). There was, however, a survival advantage in favor of the BCG-treated group (P = .03). At 5 years of follow-up, patients randomized to the surgery-alone arm were at 1.28 times the risk of dying as were similar patients treated with BCG. Further investigation disclosed that this survival advantage in favor of BCG was a result of a diminution in deaths that were non-cancer related. When analyses were conducted on which events not related to cancer recurrence were eliminated, the survival difference between the BCG and control groups became nonsignificant (P = .40); the cumulative odds at 5 years decreased from 1.28 to 1.10. The findings from this study are the first from a randomized prospective clinical trial to demonstrate that a significant disease-free survival and survival benefit can be achieved with postoperative adjuvant chemotherapy in patients with Dukes B and C carcinoma of the colon who have undergone curative resection.

Aged↗

The Intergroup Rhabdomyosarcoma Study-I. A final report.

The results of treatment of 686, previously untreated patients younger than 21 years with rhabdomyosarcoma or undifferentiated sarcoma, who were entered on Intergroup Rhabdomyosarcoma Study-I (IRS-I) were analyzed after a minimum potential follow-up time of 7 years. Patients in Clinical Group I (localized disease, completely resected) were randomized to receive either vincristine, dactinomycin, and cyclophosphamide (VAC) or VAC + radiation. At 5 years, approximately 80% of patients given either treatment were still disease-free and there was no significant difference between treatments in the overall percentages of patients surviving of 93% and 81%, respectively (P = 0.67). Patients in Clinical Group II (regional disease, grossly resected) were randomized to receive either vincristine and dactinomycin (VA) + radiation or VAC + radiation. At 5 years, 72% and 65% of the patients, respectively, were disease-free and there was no evidence of a difference between treatments (P = 0.46). The overall survival percentage at 5 years was approximately 72% for both treatments. Patients in Clinical Groups III (gross residual disease after surgery) and IV (metastatic disease) were randomized to receive either "pulse" VAC + radiation or "pulse" VAC + Adriamycin (doxorubicin) + radiation. The complete remission (CR) rate was 69% in Clinical Group III and 50% in IV, with no statistically significant difference in CR rates between treatments in either group. Those who achieved a CR had a nearly 60% chance of staying in remission for 5 years in Clinical Group III compared with approximately 30% in Clinical Group IV. The overall survival percentage at 5 years was 52% in Clinical Group III compared to 20% in Clinical Group IV (P less than 0.0001). The 5-year survival percentage for the entire cohort of 686 patients was 55%. Survival after relapse was poor, being 32% at 1 year and 17% at 2 years. The risk of distant metastasis was much greater than the risk of local recurrence within each clinical group, and there was no evidence of differing types of relapses between treatments. Primary tumors of the orbit and genitourinary tract carried the best prognosis, whereas tumors of the retroperitoneum had the worst prognosis. The authors conclude that for the therapeutic regimens evaluated there was no therapeutic advantage to including radiation in the treatment of Clinical Group I disease, or cyclophosphamide given as a daily low-dose oral regimen in the treatment of Clinical Group II disease or Adriamycin in the treatment of Clinical Groups III and IV diseases.

Adolescent↗

Postoperative radiation as adjuvant treatment for carcinoma of the oral cavity, larynx, and pharynx: preliminary report of a prospective randomized trial.

A prospective randomized trial was performed in patients with advanced squamous cell carcinomas (SCC) of the oral cavity, larynx, and pharynx to examine the effect of adjuvant postoperative radiation therapy on locoregional recurrence and survival following "curative" resection. Fifty-one patients with stage III or IV SCC treated from 1981 through 1984 were randomized to receive either surgery alone (n = 27) or surgery with postoperative radiation (n = 24). Five patients were excluded from the study after randomization because of ineligibility or protocol violations. Overall recurrence rates of 55.6% and 36.8% were noted in the surgery and surgery with adjuvant radiotherapy arms, respectively (p = NS). This trend towards a higher recurrence rate in the surgery only arm was in part due to the development of lymph node metastases in the contralateral, nonoperated neck. Thus far, no significant differences in either locoregional or overall survival have been noted between the two treatment arms. In this preliminary analysis, adjuvant postoperative radiotherapy does not appear to improve disease-free or overall survival.

Adult↗

Concepts in limb-sparing treatment of adult soft tissue sarcomas.

Pretreatment assessment of patients with soft tissue sarcomas of the extremities requires careful attention to a biopsy approach that will establish the precise diagnosis and will not compromise the subsequent definitive operative procedure. Also, staging procedures are required to evaluate the status of both local and distant sites. Limb-sparing surgery for high grade extremity soft tissue sarcomas is a feasible and appropriate approach in approximately 90% of patients with such lesions. Wide gross surgical margins around the sarcoma are the optimal operative approach. Circumstantial evidence is convincing that local treatment failure can be reduced by adjuvant regional radiation treatment when surgical margins are narrow, and end results appear to be equal to those obtained by more extensive surgical resection alone. Adjuvant radiation following operation with optimal gross surgical margins has not been established as adding benefit. Although some groups treating soft tissue sarcomas do use intraarterial chemotherapy in conjunction with these other modalities, there is, as yet, no convincing evidence that this aspect of the multimodality treatment adds to local and/or systemic disease control. The efficacy of adjuvant systemic chemotherapy for high grade soft tissue sarcomas remains to be established within the context of prospective clinical trials.

Adult↗

Extrarenal adult Wilms' tumor.

Extrarenal Wilms' tumor is a very rare disease, occurring mostly in children. Sixteen cases have been reported in the world medical literature. A case of retroperitoneal extrarenal Wilms' tumor is reported in a 36-year old white male and the literature reviewed. Pathologic examination revealed both undifferentiated renal blastoma plus differentiated areas containing immature tubules and glomeruli. No evidence of extrarenal teratomatous tissue was seen. Theories for the histogenesis of this rare tumor are discussed.

Adult↗

Paratesticular sarcoma in childhood and adolescence. A report from the Intergroup Rhabdomyosarcoma Studies I and II, 1973-1983.

This article reports on the diagnostic features, radiographic findings, staging, operative management, treatments, and treatment results for 95 children (mean age, 10 years) with paratesticular sarcoma; they were treated on the Intergroup Rhabdomyosarcoma Study (IRS) I and II protocols. Embryonal rhabdomyosarcoma (RMS) was the most common histologic subtype (97% of cases). Patients were randomly assigned to receive various therapeutic regimens according to IRS protocols. Among 81 patients (85%) with localized disease, most (57) were in Clinical Group I (localized, completely excised tumors), and 20 were in Group II (gross excision with tumor-involved, regional retroperitoneal lymph nodes or microscopic residual). Only four were in Group III (gross residual disease in the primary site or retroperitoneal lymph nodes). Three of them achieved a complete response (CR) after induction therapy and two then relapsed. The relapse-free survival (RFS) estimates at 3 years from diagnosis were 93% in Group I and 90% in Group II. Distant metastases were present at diagnosis in only 14 patients. Twelve of them achieved CR, but four subsequently relapsed; their 3-year RFS estimate was 67%. Overall, survival rates among the 95 children were excellent (89% at 3 years) compared to the entire IRS series (63%). Treatment with radical orchidectomy and chemotherapy was sufficient for Group I patients. Orchidectomy, chemotherapy, and radiation therapy were highly effective in Group II patients and in a large proportion of those with more advanced tumors. Recommendations for the diagnostic examinations and management of future patients with paratesticular sarcoma are given.

Adolescent↗

Lymphatic metastases with childhood rhabdomyosarcoma. A report from the Intergroup Rhabdomyosarcoma Study.

A review of 1415 patients without distant metastasis from the Intergroup Rhabdomyosarcoma Study (IRS) I and II revealed an overall 10% incidence of identified lymphatic spread at diagnosis, whereas 81 of 592 children with localized rhabdomyosarcoma who had grossly complete resection (and therefore with more complete pathologic data) had histologically proven lymphatic spread (14%). The percentage of patients in this latter group with nodal metastases was highest for the prostate (41%), paratesticular sites (26%), and genitourinary sites overall (24%). Sites with a small percentage of proven lymphatic involvement were the orbit (0%), nonorbital head and neck sites (7%), and truncal sites (3%), whereas the percentage of patients with nodal metastases from extremity lesions was 12%. The primary tumor mean diameter was significantly larger in the group with nodal metastases, but there was no evidence of a relationship between lymphatic spread and age, sex, or histologic subtype. Patients with lymph node metastases who had resection had a poorer survival rate (logrank P value = 0.001), with a 3-year survival estimate of 54%, compared with 78% for patients without lymphatic metastases. Patients with extremity lesions and positive lymph nodes also did poorly when compared with patients with normal nodes (P = 0.006), and a similar observation was made for patients with paratesticular sarcoma (P = 0.06).

Actuarial Analysis↗

Improved prognosis with intensive treatment of children with cranial soft tissue sarcomas arising in nonorbital parameningeal sites. A report from the Intergroup Rhabdomyosarcoma Study.

In the first Intergroup Rhabdomyosarcoma Study (IRS-I), it was found that, of 57 patients with nonorbital cranial parameningeal sarcoma treated from 1972 to 1976, 20 patients (35%) developed meningeal sarcoma and 90% (18/20) died of this complication. Since about half of these 20 patients had received inadequate radiation therapy and all had radiation therapy delayed until week 6, the treatment program was modified in December 1977 to begin radiation therapy on day 0 to the entire neuraxis and the primary tumor for all patients presenting with one or more risk factors indicating a high risk of meningeal involvement, and to administer periodic intrathecal medications to the same patients. The risk factors were intracranial extension of tumor, bony erosion at the cranial base, and cranial nerve palsy. In this report, the prognoses of two groups of patients with nonorbital cranial parameningeal sarcoma are compared: 95 patients treated before modification of the protocol in December 1977 with chemotherapy and nonintensive meningeal radiotherapy (preintensive group) and 68 patients treated subsequently with intensive meningeal radiotherapy and chemotherapy (intensive group). All patients received vincristine and actinomycin D (dactinomycin) with or without cyclophosphamide and Adriamycin (doxorubicin), according to the protocol. Radiation therapy consisted of 4000 to 5500 rad to the primary tumor in 5 to 6 weeks for most patients. The intensively treated patients also received intrathecal drugs via lumbar puncture and whole cranial or craniospinal radiation when one or more meningeal risk factors were present. In the preintensive group, the complete remission rate was 68% (65/95); the percentages of patients tumor free or alive at 3 years were 33% and 41%, respectively. In intensively treated patients, the complete remission rate was 76% (52/68); the percentages of patients tumor free or alive at 3 years were 57% and 68%, respectively. The improvements in the percentages of intensively treated patients tumor free or surviving were highly statistically significant (P less than 0.01 for both comparisons). Within the intensive treatment group, meningeal involvement at diagnosis was an unfavorable prognostic sign, since patients with no meningeal involvement had much better tumor-free survival at 3 years (81% vs. 51%) and survival (90% vs. 57%) than patients with evidence of meningeal involvement; the differences were highly statistically significant (P = 0.01).

Antineoplastic Combined Chemotherapy Protocols↗