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W U Shipley

Publications and source records attributed to W U Shipley.

At least 19 recordsLinked to original sources
PubMed1992

Deoxyribonucleic acid flow cytometry in invasive bladder carcinoma: a possible predictor for successful bladder preservation following transurethral surgery and chemotherapy-radiotherapy.

Tumor deoxyribonucleic acid (DNA) ploidy was evaluated as an objective parameter that may correlate better with the responsiveness of bladder cancer to chemotherapy plus radiotherapy than do clinical features or histopathological subtypes. A total of 40 patients with localized muscle-invading bladder cancer (clinical stages T2 to T4) underwent prospective treatment on a potential bladder preserving protocol. Tumors of 37 of the 40 patients were analyzed by DNA flow cytometry of multiple paraffin embedded specimens. Transurethral resection, neoadjuvant chemotherapy and 40 Gy. radiotherapy plus cisplatin were followed by urological reevaluation of the tumor (a complete response required a negative biopsy and a negative urine cytology study). A total of 7 noncomplete response patients underwent immediate radical cystectomy whereas the full bladder sparing treatment (radiotherapy to 64.80 Gy. plus cisplatin) was given to 23 complete response patients and 7 noncomplete response patients who were unsuited for surgery. Of the tumors 22 (59%) were purely aneuploid and 10 (27%) were purely diploid. Five tumors contained aneuploid and diploid patterns in different tumor specimens (partly diploid). Current status with a 30-month median followup in surviving patients includes an 82% overall survival rate in the aneuploid group versus 47% in the diploid/partly diploid group. Of all the patients 68% are free of invasive tumor: 82% in the aneuploid group versus 47% in the diploid/partly diploid group. By multivariate analysis pure aneuploidy was significantly (p = 0.05) correlated with freedom from invasive tumor in the bladder (either as persistence or as recurrence) and approached significance (p = 0.08) in correlation with overall patient survival. A longer observation time will be required to confirm this unexpectedly good outcome for patients with pure aneuploid tumors. We hypothesize that pretreatment DNA ploidy status may become a clinically useful prognostic factor in selecting patients for successful treatment with transurethral surgery and neoadjuvant chemotherapy plus radiotherapy.

Clinical Protocols↗
PubMed1992

The role of radiotherapy in patients with advanced seminomatous germ cell tumors. Controversies in management. Part 2.

The role of radiotherapy in the management of advanced seminomatous germ cell tumors remains controversial. The authors review the available literature, and recommend radiotherapy for stage II seminoma with bulky abdominal metastases (greater than 10 cm) under the following circumstances: As primary therapy only if the patient cannot or will not be treated with chemotherapy; as an adjuvant following chemotherapy in patients with residual masses of any size. Similar recommendations are made regarding the role of radiotherapy in the management of extragonadal seminoma outside the central nervous system.

Dysgerminoma↗
PubMed1992

Radiation therapy for testicular seminoma: controversies in the management of early-stage disease.

Subdiaphragmatic irradiation remains the standard treatment for patients with stage I and IIA testicular seminoma. Elective mediastinal irradiation is not indicated. In well-selected patients with stage I disease, aggressive surveillance may be a reasonable alternative to elective irradiation. We believe that bipedal lymphangiography is useful in staging, radiation field design, and follow-up. Other controversies in the radiotherapeutic management include the optimal radiation dose and appropriate target volume.

Dysgerminoma↗
PubMed1992

Radiotherapy and chemotherapy in invasive bladder cancer with potential bladder sparing.

The standard treatment in the United States for patients with muscle infiltrating tumors is radical cystectomy with or without radiation treatment. The results of such treatment have been generally unsatisfactory, with 40% or more patients developing systemic disease with a 5-year survival rate of less than 50%. Combination chemotherapy employing both cisplatin and methotrexate can produce a 30% to 50% clinical complete response rate (negative biopsy, negative urinary cytology) of the primary tumor. Although the optimal combination of chemotherapeutic agents has not yet been determined, it is unlikely that combination chemotherapy alone, even in completely responding patients, will be adequate to rid the bladder of a primary invasive transitional cell carcinoma. Additional therapy by either surgery or external beam radiotherapy seems warranted owing to the high likelihood that there will be residual microscopic tumor in the bladder. Concomitant systemic chemotherapy and external beam radiotherapy produces complete remissions in 65% to 90% of patients. Follow-up of from 3 to 5 years following full chemoradiotherapy will be necessary to be certain that the bladder has been sterilized of cancer. Combined cisplatin and external beam radiation (using a boost technique that spares the section of the bladder uninvolved with tumor) does not seem to enhance local soft-tissue toxicity (relative to the radiotherapy alone) with the exception of the neurotoxicity seen with intra-arterial cisplatin. Debulking TURB tumor appears to improve the local success rate for patients being considered for bladder preservation with the use of the combination of systemic chemotherapy and/or radiotherapy. Not all patients respond to concomitant chemotherapy and radiation therapy. Our current approach is that the selection process must be carried on at several points during the treatment. Only patients who respond completely to the initial courses of chemotherapy and radiation should be carried to a full radiation dose. In the absence of a complete response following upfront chemotherapy and 4000 cGy in combination with additional cisplatin courses, cystectomy at that point is the recommended treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Cisplatin↗
PubMed1991

Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706.

Significant late intestinal and urinary morbidity from external beam irradiation for adenocarcinoma of the prostate has been a constant concern of both the urologist and the radiation oncologist. We analyzed two large Radiation Therapy Oncology Group trials (7506 and 7706) using primary irradiation in the treatment of local or locoregional adenocarcinoma of the prostate to assess morbidity via the Radiation Therapy Oncology Group scoring scheme (grade 1-5). One thousand twenty patients were treated in total with a minimum follow-up of 7 years in the surviving patients. There was a 3.3% incidence of intestinal complications defined as grade 3 toxicity or more with .6% of patients experiencing bowel obstruction or perforation. Urinary complications defined as grade 3 toxicity or more were found in 7.7% of patients with only 0.5% experiencing morbidity that would require a major surgical intervention such as laparotomy, cystectomy, or prolonged hospitalization. Intestinal and urinary complications were evaluated in reference to several parameters that might have an impact on their incidence (i.e., previous laparotomy, stage of disease, hypertension, positive lymph nodes, previous transurethral resection, total dose, and energy of accelerator used). Only total dose (greater than 70 Gray) was found to have a significant impact on the incidence of the urinary complications. None of these factors had a significant impact on the incidence of intestinal complications. These data from two large multi-institutional trials represent a fair estimate of the actual incidence of major intestinal and urinary complications from external beam irradiation in the management of local and locoregional adenocarcinoma of the prostate. Since the incidence of these major complications remains very low, we believe that external beam irradiation remains an excellent alternative to radical prostatectomy in the management of these patients.

Adenocarcinoma↗
PubMed1991

Biopsy after external beam radiation therapy for adenocarcinoma of the prostate: correlation with original histological grade and current prostate specific antigen levels.

We obtained post-irradiation biopsies in 37 men with initially stage T3 prostatic adenocarcinoma treated by external beam radiotherapy. Eligibility for post-irradiation biopsy included no clinical local failure, interval since treatment of 24 months or more and no endocrine therapy. Of the 37 patients 23 (62%) had negative biopsies while 14 (38%) had positive biopsies. Of 23 patients whose original cancer was well or moderately differentiated 18 (78%) had negative biopsies, compared to only 5 of 14 (36%) of those with poorly differentiated cancer (p less than 0.03). Among 19 patients whose current serum prostate specific antigen (PSA) value is less than 2.5 ng./ml. 15 (79%) had negative biopsies, compared to only 4 of 14 (29%) with a PSA level of greater than 2.5 ng./ml. (p less than 0.02). These results strongly suggest that there is a low probability of positive post-irradiation biopsy regardless of its significance in men with a normal prostate by palpation and a normal serum PSA value. However, short followup since biopsy precludes analysis of the predictive value of post-irradiation biopsy on long-term local and distant disease status.

Adenocarcinoma↗
PubMed1991

Role of lymphangiography in staging testicular seminoma.

Bipedal lymphangiography (LAG) and abdominal/pelvic computerized tomography (CT) are both useful in evaluating retroperitoneal lymph nodes in early-stage testicular seminoma. Fifty-four patients who had both radiologic studies performed between 1982 and 1986 were identified, and their films were reviewed. Four patients had evidence of retroperitoneal lymph node metastases on both CT and LAG. Of the 50 patients who had normal findings on CT scan, 39 (78%) had a normal LAG and 11 (22%) had a positive LAG. All 11 patients had architectural abnormalities within normal-sized nodes. No patient had positive findings on CT with negative LAG. In addition to aiding in staging, LAG is very useful in designing radiation treatment portals. Therefore, we believe that LAG can continue to play an important role in the accurate staging and treatment of patients with testicular seminoma.

Dysgerminoma↗
PubMed1991

Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy.

Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow-up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials.

Adult↗
PubMed1991

The role of radiation therapy in the treatment of testicular germ cell tumors.

Infradiaphragmatic radiotherapy remains the treatment of choice for patients with stage I and II (small volume) testicular seminoma. With this approach, the disease-free survival rate exceeds 90% to 95%, and the ultimate disease-free survival rate (including salvage) is 95% to 100%. Initial therapy for patients with large-volume stage II, III, and IV disease should include multiagent systemic chemotherapy. Involved field radiotherapy is recommended for these patients following the chemotherapy, especially in patients with residual masses larger than a few centimeters. Although not used frequently in the United States, infradiaphragmatic radiotherapy is a viable treatment option for patients with clinical stage I testicular nonseminomas. Such therapy results in approximately an 85% to 90% relapse-free survival rate, with an ultimate survival rate (including salvage) approaching 100%. Initial therapy for patients with stage II or greater disease generally should include chemotherapy and/or surgery. Radiotherapy is often useful as post-chemotherapy consolidation, especially for unresectable masses. For extra-gonadal seminomas, radiotherapy is useful as definitive therapy for small-volume disease and as consolidative therapy (postchemotherapy) for more advanced disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Interval report of a phase I-II study utilizing multiple modalities in the treatment of invasive bladder cancer. A bladder-sparing trial.

Clinicians at the Massachusetts General Hospital have used two cycles of methotrexate, cisplatin, and vinblastine (MCV) before radiotherapy and cisplatin in 53 patients with muscle-invasive bladder cancer. Eleven patients did not complete the protocol, but overall, the toxicity was not formidable. Of the total patients accessioned, 34 are alive. Of the 34 patients in the series who completed the full treatment protocol, the estimated survival rate at 54 months is 77%. This interim analysis suggests that the treatment is achieving at least limited success in saving lives and bladders.

Adult↗
PubMed1991

Management of spinal cord compression secondary to metastatic prostatic carcinoma.

Spinal cord or cauda equina compression from prostatic cancer is an oncologic emergency necessitating prompt evaluation and treatment. The strong correlation between pretreatment motor status and treatment outcome underscores the importance of immediate treatment before further neurologic deterioration and before the damage to the spinal cord becomes permanent. Patients with known osseous metastases should be alerted by their clinicians to seek medical help within hours should they develop weakness in an extremity. Prompt MRI of the entire spine should be done prior to treatment. Myelography should be reserved for those patients who cannot undergo a technically adequate or expeditious MRI study. The convenience of MRI relative to myelography allows clinicians to diagnose actual or impending spinal cord compression earlier. High-dose steroids (dexamethasone) should be instituted immediately, and endocrine therapy should be started if not already in use. Ambulatory and moderately paraparetic patients seem best treated initially with radiation alone. Immediate surgical decompression should be used in patients with an expected lifespan of at least 6 months who deteriorate during radiation, who have had previous radiation to the involved site, or who have a potentially correctable unstable spine. In addition, paraplegic patients or severely paraparetic patients with recent neurologic deterioration should be treated with immediate surgical decompression if they are judged reasonably able to tolerate the surgery. These patients should then receive postoperative radiation treatment.

Humans↗
PubMed1990

Bladder cancer. Advances in laboratory innovations and clinical management, with emphasis on innovations allowing bladder-sparing approaches for patients with invasive tumors.

In the present decade important progress has been made in the understanding of the biology and management of bladder cancer. Experimental laboratory models and new investigative tools have revealed potentially important prognostic markers and have led to an improved understanding of the histogenesis of the disease. Advances in the management of superficial bladder cancer (intravesical chemotherapy or immunotherapy, improved urinary cytology, laser technology, flexible fiberoptic cystoscopy, and photodynamic therapy) have, in some subgroups, improved tumor control while decreasing patient complications. For invasive bladder cancer (invasive of bladder muscle or beyond) improved techniques of cystectomy and radiotherapy have reduced the complications of treatment and may have contributed small but important improvements in cure. A major improvement in the last decade has occurred in objective remission rates with chemotherapy for patients with metastatic bladder cancer. From 20% to 40% of patients achieve a complete remission, and 10% to 20% may survive for more than 3 years. Randomized Phase III trials are currently in progress and must be completed to define the true role of multidrug chemotherapy in patients with metastatic disease and to validate data from the regimens of cyclophosphamide, methotrexate, and vincristine (CMV) and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) before any of these approaches to treatment can be considered of proven benefit. Preliminary data from the Massachusetts General Hospital are presented of a potentially effective approach to select patients with invasive tumor for successful bladder preservation. In this approach transurethral debulking surgery is combined with upfront CMV chemotherapy plus cisplatin and 4000 cGy. If tumor is found on cystoscopic reevaluation with biopsy and cytology immediately following cisplatin and 4000 cGy, cystectomy is performed; if not, consolidation by a radiation boost to 6480 cGy plus cisplatin is given. The approach is fairly well tolerated, allows cystectomy without undue complications, has yielded a 88% complete response rate in patients selected for bladder preservation, and resulted in 90% of patients free of distant metastases with follow-up ranging from 6 to 30 months. A randomized Phase III trial with and without neoadjuvant MCV chemotherapy for selective bladder preservation is now under way and accruing well.

Actuarial Analysis↗
PubMed1990

Spermatic cord sarcomas: sonographic and CT features.

Five patients with sarcomas of the spermatic cord were imaged with sonography and/or computed tomography (CT). The former modality is most helpful in demonstrating the extratesticular origin of the mass and evaluating its scrotal extension for local staging. CT is necessary for pelvic staging and searching for distant metastasis. The fat in liposarcomas was easily identified by CT, although it was not echogenic on sonography. Sonography should be the primary imaging modality for scrotal or inguinal masses. If a neoplasm is found, CT should be used for staging, prior to definitive surgical treatment.

Aged↗
PubMed1990

Preliminary results in invasive bladder cancer with transurethral resection, neoadjuvant chemotherapy and combined pelvic irradiation plus cisplatin chemotherapy.

Preliminary data are presented of a clinically feasible pilot study to select a significant subgroup of patients among those with muscle-invading bladder tumors for local cure and bladder preservation, while also to offer all patients the possibility of preventing the development of distant metastases. Transurethral debulking surgical resection was combined with neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy plus 2 additional courses of cisplatin and 4,000 cGy. If tumor was found on cystoscopic re-evaluation by biopsy and for cytology after cisplatin and partial irradiation (4,000 cGy.) immediate cystectomy was advised. If tumor was not found consolidation by a radiotherapy boost to a total of 6,480 cGy. plus 1 additional course of cisplatin was given. Of 53 consecutive patients the planned treatment was completed in 42 (79%). With a median followup of 26 months (range 15 to 42 months), 72% of all entered patients were alive, 70% have not required cystectomy and 74% have not had distant metastases. Among the 42 patients who completed the planned protocol chemotherapy dose reductions were required in 39% for stomatitis, bone marrow depression and/or renal dysfunction. There were 2 serious complications but no treatment-related sepsis, deaths or significant renal dysfunction. Eight patients underwent immediate radical cystectomy because of positive biopsy and/or cytology results after 4,000 cGy., while 34 completed full chemotherapy and radiotherapy without any significant bladder or bowel injury. Of 42 patients 22 (52%) have maintained the bladder without any recurrence, and of those selected for full chemotherapy and radiotherapy this number increased to 65%. To date 12 patients have persistent or recurrent bladder tumors: 5 (15%) had invasive tumors treated by cystectomy and 7 (21%) had carcinoma in situ treated by intravesical therapy. The true success of this or other selective bladder-preserving treatments will require 3 to 5 years of followup to be confident that such treatment has sterilized the bladder of cancer. This feasibility study has been clinically practical, modestly well tolerated and encouraging for the significant proportion of patients with a sustained complete response and for the 70% over-all survival rate at 2 years. To evaluate critically the efficacy of methotrexate, cisplatin and vinblastine chemotherapy in the prevention of occult distant micrometastases and in increasing the rate of successful bladder preservation, in May 1988 we began a randomized phase 3 trial with and without neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy.

Aged↗
PubMed1990

Testicular seminoma: clinical and pathological features that may predict para-aortic lymph node metastases.

Patients with clinical stage I testicular seminoma usually receive elective para-aortic lymph node radiation after orchiectomy, which is effective in controlling subclinical microscopic disease. However, the majority of patients with clinical stage I seminoma do not harbor occult metastases and, therefore, do not require elective nodal treatment. Vascular space invasion by the primary testis tumor recently has been shown to be an important predictor of metastases in nonseminomatous tumors but no such information exists to date in pure seminoma. Therefore, patients with clinical stage I testicular seminoma were compared to clinical stage II to IV cancer patients with respect to the presence of several features of the primary tumor. Vascular space invasion was identified significantly less frequently in stage I cancer patients (17%, 5 of 29) than in those with stage II or greater disease (39%, 11 of 28, p equals 0.03, 1-tailed t test). Microscopic invasion of the tunica and rete testis, and necrosis also were identified slightly more frequently in the higher stage cancer patients. Of the 12 patients with a maximum tumor dimension of more than 6 cm. 9 (75%) were in the stage II or higher group. Patient age, symptom duration and presenting complaint were similar in the 2 groups. Many higher stage cancer patients did not exhibit aggressive histological characteristics and, therefore, the absence of these features cannot be used to select patients for surveillance. On the other hand, patients with clinical stage I tumors that exhibit vascular space invasion may have an increased rate of occult para-aortic lymph node metastases. Therefore, the presence of vascular space invasion may be a useful criterion for exclusion of patients from surveillance protocols. Confirmatory data are needed before a final recommendation can be made.

Adult↗