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N M Heney

Publications and source records attributed to N M Heney.

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

Natural history of superficial bladder cancer. Prognostic features and long-term disease course.

Superficial bladder cancer or, more accurately, stages Ta, T1, and Tis encompass a spectrum that ranges from innocuous to life-threatening lesions. There is growing evidence that Ta grade 1 tumors rarely become invasive; although when there is associated carcinoma in situ or severe dysplasia, the risk of invasiveness increases. Carcinoma in situ is treacherous, with unpredictable behavior. Predictors of recurrence and progression are beginning to be identified for the various superficial tumors.

Carcinoma in Situ↗
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

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

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↗
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

Can chemo-radiotherapy plus transurethral tumor resection make cystectomy unnecessary for invasive bladder cancer?

The standard treatment for muscle-invading bladder tumors is, in the US, radical cystectomy +/- radiation; in Europe, it is radical radiotherapy. Neither of these therapies alone is wholly satisfactory. Suggested improvements in the complete response rates of the primary tumor have been reported with combination chemotherapy and with chemo-radiotherapy. Selecting for full chemo-radiotherapy only patients having a biopsy-proven CR to initial chemotherapy and/or to 4,000-4,500 cGy of radiation may further increase the success of bladder-preserving programs and not compromise survival (relative to immediate cystectomy), but this has not yet been proven. Randomized trials of neoadjuvant chemotherapy must be finished before its efficacy in subclinical systemic disease will be known. Likewise, proof of the efficacy of neoadjuvant chemotherapy in improving bladder preservation by chemo-radiotherapy must await completion of randomized trials. Three to five years of follow-up will be necessary before chemo-radiotherapy can be recommended as curing the bladder of cancer.

Combined Modality Therapy↗
PubMed1988

Invasive bladder carcinoma: preliminary report of selective bladder conservation by transurethral surgery, upfront MCV (methotrexate, cisplatin, and vinblastine) chemotherapy and pelvic irradiation plus cisplatin.

Methotrexate, Cisplatin, and Vinblastine (MCV) was followed by Cisplatin plus radiation therapy in 19 patients with muscle-invading clinical Stage T2-4NXM0 transitional cell carcinoma of the urinary bladder (including cystectomy candidates), to achieve local control and prevent distant metastases. Radical cystectomy was recommended for all patients who failed to reach a complete response (CR = biopsy negative and cytology not positive) following MCV and Cisplatin X 2 plus 4000 cGy. Completely responding patients, and those partially responding patients unsuited for cystectomy, were selected for bladder conservation treated with additional irradiation to the bladder tumor volume (total 6,480 cGy) plus one additional Cisplatin treatment. Dose reductions were required for stomatitis in 26%, mild bone marrow depression in 58%, and renal toxicity in 5% of the patients. During the Cisplatin/4000 cGy, mild dysuria occurred in 68% of patients and 36% had mild bowel hyperactivity. Serious complications have occurred in two patients to date. One patient had recurrent pulmonary emboli, marked reduction in bladder capacity, and diarrhea. A second had bladder perforation during cystoscopic evaluation after MCV and a small bowel obstruction after Cisplatin and 4000 cGy. There was no treatment-related sepsis. Three patients had initial complete transurethral resection of their tumors and therefore 16 patients are evaluable for tumor responsiveness to this protocol. Four patients (25%) were biopsy negative and cytology negative, whereas three additional patients (19%) were biopsy negative but cytology positive following initial MCV. Six patients (38%) were biopsy negative and cytology negative whereas three additional patients (19%) were biopsy negative and cytology positive following MCV and Cisplatin X 2 plus 4000 cGy pelvic radiation. Of the entire group, 9 patients were treated with full-dose radiotherapy. All of these patients are alive without evidence of tumor on rebiopsy of the original tumor site, but one has a persistent positive cytology. Seven patients had a radical cystectomy and 6 are disease free. The treatment of 3 patients deviated from the protocol. Overall, only one patient has developed distant metastases and currently 84% of the patients are disease-free, although follow-up is short. To date, this feasibility study has been clinically practical and well tolerated. The proportion of CR's suggests that this program may prove to be an organ-sparing and curative approach for a significant number of patients, but more experience and follow-up are required.

Adult↗
PubMed1988

Intravesical thiotepa versus mitomycin C in patients with Ta, T1 and TIS transitional cell carcinoma of the bladder: a phase III prospective randomized study.

A prospective randomized clinical trial was conducted by the National Bladder Cancer Group to compare thiotepa and mitomycin C in ablating residual Ta, T1 and TIS transitional cell carcinoma of the bladder. Eight weekly instillations were given followed by cystoscopy 4 weeks after the treatment was stopped. The over-all complete response rate based on cystoscopy and either biopsy or cytology was 26 per cent for thiotepa versus 39 per cent for mitomycin C (p equals 0.08). The greatest efficacy was seen in the Ta group with mitomycin C demonstrating superiority over thiotepa. Patients with negative cystoscopy and biopsy but who had positive cytology were considered to be partial responders. When partial and complete responders were combined the over-all response rate was 53 per cent for thiotepa and 63 per cent for mitomycin C (p equals 0.23). Patients with TIS appeared to respond equally to thiotepa and mitomycin C. Toxicity included urinary frequency in 22 of the 73 patients in the thiotepa arm and 31 of the 76 patients receiving mitomycin C. A rash was observed in 2 of the thiotepa group versus 14 of the mitomycin C group. Bone marrow depression occurred in 15 patients receiving thiotepa and in 12 receiving mitomycin C.

Administration, Intravesical↗
PubMed1988

Intravesical chemotherapy: how effective is it?

Intravesical chemotherapy has been shown to reduce or prevent recurrence of low-grade, low-stage transitional cell tumors of the bladder. Thiotepa, mitomycin C, doxorubicin, and bacillus Calmette-Guérin (BCG) are the drugs most widely used for intravesical chemotherapy in the United States; only thiotepa has FDA approval for use within the bladder. Results of studies with these agents are reviewed. Prospective, randomized studies are needed to determine the ability of the agents to prevent progression of high-grade tumors to muscle invasion.

Administration, Intravesical↗
PubMed1988

Radiation therapy for localized prostate carcinoma: experience at the Massachusetts General Hospital (1973-1981).

The success following irradiation in 370 patients with clinically localized prostate carcinoma was measured by overall patient survival as well as the cumulative incidence with time of treated patients who developed either local tumor regrowth or progression with distant metastases. With a minimum follow-up of 5 years in living patients, we evaluated the cumulative frequency curves using both univariate and multivariate (Cox) analyses. Overall patient survival and probability of progression with distant metastases were significantly influenced by initial tumor stage and the degree of histologic differentiation. The results at 8 years are significantly better for patients with T2 (B) tumors (local regrowth in 8%, distant metastases in 18%) than for patients with T3-T4 (C) tumors (local regrowth in 28%, distant metastases in 60%). Patient tolerance of external-beam radiation therapy was carefully analyzed in 121 consecutively treated patients in 1980 and 1981 for subsequent radiation-related sequelae. Minor transient intestinal and urologic sequelae were observed in 21% and 23% of the patients, respectively. These mild to moderate symptoms resolved in all but 7% of the patients who are continuing with mild symptoms. One patient had a major complication, i.e., a cystectomy required for persistent bleeding. Erectile potency has been maintained in 63% of potent patients. No specific benefit or detriment in outcome was seen in the minority of 51 patients who were irradiated by iodine-125 implantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1986

Ureteroscopy: the initial experience.

A prospective study of our first 81 cases of ureteroscopy using extended length rigid endoscopes was performed. Of 55 stone manipulations attempted in 51 patients by 6 endoscopists 38 (69 per cent) were successful. Analyzed sequentially, removal was successful in 12 of 23 attempts (52 per cent) among the initial 40 patients and in 26 of 32 (81 per cent) among the subsequent 41 patients. Of 11 calculi larger than 1 cm. and of 23 positioned above the iliac vessels 7 (64 per cent) and 11 (48 per cent), respectively, were removed successfully. Disimpaction by ureteroscopic manipulation combined with extracorporeal shock wave lithotripsy was successful in 4 cases of upper ureteral calculi not treatable by extracorporeal shock wave lithotripsy alone. Diagnostic and therapeutic uses of the ureteroscope in addition to treatment of ureteral calculi have included the delineation of ureteral filling defects (9 patients), fulguration of known low grade tumors (4) and dilation of ureteral strictures (5). In 10 patients information was obtained endoscopically that was not possible by standard diagnostic techniques. The direct visual approach to the ureter has distinct advantages over blind ureteral instrumentation.

Adult↗
PubMed1985

Full-dose irradiation for patients with invasive bladder carcinoma: clinical and histological factors prognostic of improved survival.

We reviewed the outcome of 55 patients treated from 1974 to 1982 by full-dose radiation therapy (6,400 to 6,800 rad) to identify factors associated with tumor radioresponsiveness and patient cure. All patients had histological proof of muscle invasion by tumor. Of the patients 8 (14 per cent) had clinical stage T2, 29 (53 per cent) stage T3 and 18 (33 per cent) stage T4 disease. Thirteen patients are alive, all but 2 without evidence of cancer. Survivors include 1 of 9 patients who underwent salvage cystectomy for a local recurrence. The actuarial 5-year survival rate for the entire group was 28 per cent, with a corrected survival of 33 per cent. Median survival was 2.3 years. Corrected survival for patients with stages T2 and T3 disease was 45 per cent versus 9 per cent for those with stage T4 cancer (p equals 0.009). Within the group with stages T2 and T3 cancer (all with proof of muscle invasion) the most striking prognostic factor was papillary surface histological findings, with local control by radiation therapy alone of 63 per cent versus 20 per cent in the group with solid or flat tumors (p equals 0.01), and corrected 5-year survival of 62 per cent (papillary) versus 0 per cent (flat or solid) (p equals 0.002). Other significant prognostic factors for 5-year survival in this group were extent of transurethral resection (54 per cent complete versus 17 per cent incomplete, p equals 0.009) and ureteral obstruction on excretory urography (47 per cent without versus 14 per cent with, p equals 0.01). Our results suggest that full-dose radiation therapy can be offered to patients with muscle-invading bladder cancer, with a relatively higher probability of success in those with less advanced tumors by clinical stage, papillary surface histological findings and no ureteral obstruction, and in whom a complete transurethral resection is possible.

Aged↗
PubMed1985

First-line chemotherapy of superficial bladder cancer: mitomycin vs thiotepa.

A prospective randomized study has been conducted to compare the efficacy and toxicity of thiotepa with mitomycin in patients with transitional cell carcinoma of the bladder. The 156 patients entered to date in the study were distributed by tumor grade and stage as follows: grade 1, 36 patients; grade 2, 49 patients; grade 3, 18 patients; Ta, 67 patients; T1, 33 patients; and TIS, 56 patients. All patients had tumor present in the bladder on entry to the study and after eight instillations at weekly intervals; evaluative cystoscopy and biopsy were performed four weeks later. Preliminary analysis of 156 patients indicated on overall complete response of 39 per cent for mitomycin and 27 per cent for thiotepa, which is a statistically significant difference (P = 0.02). Moderate to severe leukopenia was the most common single toxic effect with thiotepa, and a rash was the most common single toxic effect with mitomycin.

Carcinoma, Transitional Cell↗