Ramananda M. Shetty

Cisplatin and 5-fluorouracil in the primary management of squamous esophageal cancer

A combined treatment program consisting of chemotherapy with cisplatin and infusion 5‐fluorouracil (5‐FU) for three cycles followed by esophagectomy or radiation, or both, has been conducted in 26 patients with squamous cancer of the esophagus localized to the primary site. Eleven patients had objective evidence of partial or complete response to the chemotherapy. Fourteen patients were operated on and ten underwent total esophagectomy. Drug toxicity was considerable with severe mucositis and myelosuppression occurring in 11 and seven patients, respectively. There were no drug‐related deaths. Median survival is 17.8 months. Ten patients have lived more than 2 years. Six of these patients have undergone total thoracic esophagectomy after the induction chemotherapy. Determination of the ultimate benefits of combined modality therapy may require prospective randomized trials isolating the major treatment components but our data suggest that chemotherapy contributes to improved results in this disease and that drug therapy is emerging as an integral component of combined therapy.

The role of adjuvant irradiation following primary prostatectomy, based on histopathologic extent of tumor

One hundred twenty-three patients who underwent primary prostatectomy at Northwestern Memorial Hospital during the-years 1976 to 1985 are reviewed. The patients were divided into three groups: Group 1 (50 patients) comprises patients with tumor well-contained within the prostate and without perineural, perivascular, or lymphatic (NVL) invasion; Group 2 (57 patients) comprises patients with more extensive tumor extending through or to the prostatic capsule, extending to or near the surgical margin, involving seminal vesicles, or having NVL invasion; Group 3 (16 patients) comprises those patients who received immediate postoperative irradiation. The actuarial 10-year local control rates of Group 1 (88%) and Group 3 (100%) were statistically superior to that of Group 2 (72%), p less than 0.05. The actuarial 10-year disease-free survival rate of Group 1 (72%) is statistically superior to that of Group 2 (56%), p less than 0.01; the difference in 10-year disease-free survival between Group 2 (56%) and Group 3 (64%) did not reach statistical significance. Ten-year actuarial survival statistics are 64%, 80%, and 76% for Groups 1, 2, and 3 respectively. There was no statistically significant difference in actuarial survival among any of the groups. Patients with tumor extending to or through the prostatic capsule, extending to or near the surgical margins, involving the seminal vesicles, or having NVL invasion all may benefit from adjuvant irradiation in the immediate perioperative period.

Biochemical disease-free survival following adjuvant and salvage irradiation after radical prostatectomy

PURPOSE To present the biochemical cure rates (biochemically no evidence of disease) after external irradiation (RT) in patients with high-risk prostate cancer after radical prostatectomy. METHODS AND MATERIALS Seventy-six patients who underwent radical prostatectomy and subsequent RT were included in this analysis. No patient received hormonal therapy. Adjuvant RT was administered in 35 patients (46%), and 41 patients (54%) underwent salvage RT. After prostatectomy, the Gleason score was <7 in 87%, and 24% had seminal vesicle invasion. The median RT dose in the adjuvant RT and salvage RT groups was 60 Gy and 65 Gy, respectively. The biochemical cure rate was defined as a serum prostate-specific antigen of < or =0.2 ng/mL. RESULTS The overall 5-year Kaplan-Meier biochemical control rate from the end of RT was 70%. The 5-year biochemical cure rate for adjuvant RT was significantly superior to that after salvage RT (86% vs. 57%). The significant predictors of biochemical failure were seminal vesicle invasion in the adjuvant RT group and the presence of Gleason grade 4 or 5 in the salvage RT group. The clinical local control rate in the prostate bed was 100%. CONCLUSION This report demonstrates the efficacy of RT in achieving high biochemical cure rates after radical prostatectomy. Additional clinical studies are required to determine the optimal treatment of patients at high risk of biochemical failure after postprostatectomy RT.

Role of radiation therapy in the management of carcinoma in situ of the larynx

Twenty-one patients with carcinoma in situ of the larynx were treated with definitive irradiation from 1959 to 1987. The in situ changes were limited to 1 vocal cord in 19 patients, and to both vocal cords in 1 patient. One patient demonstrated extensive in situ changes involving the vocal cords bilaterally, as well as the anterior commissure, with both supraglottic and infraglottic extension. The mean follow-up from completion of treatment was 6.2 years, with a median of 50 months. Definitive irradiation resulted in a local control rate of 95%. The patient with extraglottic spread of in situ changes experienced a local failure 7 months after completion of treatment and, despite surgical salvage, died of local recurrence. This patient represents the only recurrence in our series. Our data suggest that radiation therapy can provide excellent control in carcinoma in situ limited to the true vocal cord.

Preoperative combination chemotherapy for advanced stage head and neck cancer. Promising early results

We treated 19 consecutive patients with cisplatin, bleomycin, and methotrexate before definitive surgery or radiation therapy. Fourteen patients (74 percent) had partial or complete tumor regression after chemotherapy. With a minimum follow-up time of 27 months, none of the 4 patients who had a major histologic response relapsed, and only 2 of the remaining 15 patients continued disease-free. The achievement of a complete histologic response after preoperative chemotherapy may correlate with long-term disease-free survival after surgery and radiation therapy for head and neck cancer.

Local graft irradiation after failure of modern immunosuppression in acute cellular and vascular graft rejection.

PURPOSE With improved chemical immunosuppressive agents, approximately 90% of rejection episodes can be reversed. However, in situations of failed immunosuppression, graft loss becomes inevitable. Our objective is to assess the efficacy of local graft irradiation (LGI) as an effort of last resort in a contemporary group of patients in whom graft failure to irreversible cellular and vascular rejection is imminent. METHODS AND MATERIALS A total of 308 renal transplantations were performed at our institution from 1992 to 1995, and an overall 1-year graft survival rate of 90% has been seen as a result of improvement in chemical immunosuppression. However, 6 patients were referred for LGI when all other measures failed to reverse the rejection crisis. Parameters that were studied in these patients included graft function and postirradiation graft histology. RESULTS Irradiation was associated with reversal of the rejection crisis and resulted in documented histological long-term graft survival in 1 of the 6 patients (17%). Two of the six patients (33%) had reversal of the rejection episode based on postirradiation biopsy of the renal allograft. Three of the six patients showed some level of clinical improvement of graft function for varying periods of time. One patient maintained stable allograft function without deterioration and with continued independence from hemodialysis. One recipient died from sepsis despite histologic improvement after irradiation. CONCLUSIONS Our impression is that LGI is indicated when all other measures have failed to reverse an acute rejection episode in the transplanted renal allograft. The role of radiation in this setting should be studied further.

Adjuvant Doxorubicin Hydrochloride and Radiation in Stage D Bladder Cancer: A Preliminary Report

The prognosis of patients with stage D bladder cancer is dismal. This report expands the results of our efforts to modify the clinical course of such patients by administration of doxorubicin hydrochloride sandwiched around pelvic radiation. Pathologic stage D bladder cancer was recognized in 19 patients by evaluation of tissue obtained by radical cystectomy and pelvic lymphadenectomy (8), pelvic lymph node dissection (5) or biopsies (3), ileal conduit and pelvic lymph node biopsy (1), or transurethral biopsy of the bladder and prostate (2). Treatment of these patients with doxorubicin hydrochloride before and after radiation was initiated 3 to 4 weeks postoperatively. The treatment regimen consisted of 1) 60 mg. per M.2 doxorubicin intravenously every 3 weeks for 3 cycles, 2) 5,000 rad external radiation to the entire pelvis in 5 to 6 weeks and 3) doxorubicin for 5 cycles. The observed survival rates were 37 per cent at 3 years and 28 per cent at 5 years. The median survival time was 16 months. Five patients had no evidence of disease 13 to 63 months postoperatively. One patient underwent salvage cystectomy for recurrent bladder carcinoma at 33 months and had no evidence of disease at 74 months. One patient was alive with recurrent disease at 13 months. Three patients who died did not complete the protocol owing to metastatic disease, 8 lived 6 to 52 months without recognized disease and died of metastases, and 1 died of a second primary. The extent of surgical excision was not associated significantly with survival. Of 8 patients treated with radical cystectomy 7 suffered a significant obstruction of the small bowel that required decompression or bypass surgery and all 7 recovered completely. These preliminary observations indicate encouraging results with a high but manageable morbidity for this regimen.

Treatment of stage D bladder cancer with adjuvant doxorubicin hydrochloride and radiation

pathologic Stage D bladder cancer was recognized in 16 patients by evaluation tissue obtained by radical cystectomy and pelvic lymphadenectomy (7), pelvic lymph node dissection (3) or biopsies (3), ileal conduit and pelvic lymph node biopsy (1), or transurethral biopsy of the bladder and prostate (2). Treatment of these patients with radiation preceded and followed by doxorubicin hydrochloride (Adriamycin) was initiated three to four weeks postoperatively. The treatment regimen consisted of the following: (1) doxorubicin 60 mg/M2 intravenously every three weeks for three cycles; (2) 5,000 rad external radiation to the whole pelvis in five to six weeks; and (3) doxorubicin for five cycles. The mean survival was twenty-three months. The survival rate was as follows: one year, 10 of 15 patients at risk; two years, 6 of 11; three years, 5 of 9; four years, 1 of 4; and five years, 0 of 2. Ten patients died six to thirty-six months (mean 13.6) postoperatively. In 6 of the patients significant obstruction of small bowel developed. These preliminary observations indicate encouraging therapeutic results with an acceptable morbidity for this regimen.